DNA damage theory of aging

From Wikipedia, the free encyclopedia

The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damages. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly (by increasing apoptosis or cellular senescence) or directly (by increasing cell dysfunction).

Several review articles have shown that deficient DNA repair, allowing greater accumulation of DNA damages, causes premature aging; and that increased DNA repair facilitates greater longevity. Mouse models of nucleotide-excision–repair syndromes reveal a striking correlation between the degree to which specific DNA repair pathways are compromised and the severity of accelerated aging, strongly suggesting a causal relationship. Human populations studies show that single-nucleotide polymorphisms in DNA repair genes, causing up-regulation of their expression, correlate with increases in longevity. Lombard et al. compiled a lengthy list of mouse mutational models with pathologic features of premature aging, all caused by different DNA repair defects. Freitas and de Magalhães presented a comprehensive review and appraisal of the DNA damage theory of aging, including a detailed analysis of many forms of evidence linking DNA damage to aging. As an example, they described a study showing that centenarians of 100 to 107 years of age had higher levels of two DNA repair enzymes, PARP1 and Ku70, than general-population old individuals of 69 to 75 years of age. Their analysis supported the hypothesis that improved DNA repair leads to longer life span. Overall, they concluded that while the complexity of responses to DNA damage remains only partly understood, the idea that DNA damage accumulation with age is the primary cause of aging remains an intuitive and powerful one.

In humans and other mammals, DNA damage occurs frequently and DNA repair processes have evolved to compensate. In estimates made for mice, DNA lesions occur on average 25 to 115 times per minute in each cell, or about 36,000 to 160,000 per cell per day. Some DNA damage may remain in any cell despite the action of repair processes. The accumulation of unrepaired DNA damage is more prevalent in certain types of cells, particularly in non-replicating or slowly replicating cells, such as cells in the brain, skeletal and cardiac muscle.

DNA damage and mutation

8-Hydroxydeoxyguanosine

To understand the DNA damage theory of aging it is important to distinguish between DNA damage and mutation, the two major types of errors that occur in DNA. Damage and mutation are fundamentally different. DNA damage is any physical abnormality in the DNA, such as single and double strand breaks, 8-hydroxydeoxyguanosine residues and polycyclic aromatic hydrocarbon adducts. DNA damage can be recognized by enzymes, and thus can be correctly repaired using the complementary undamaged sequence in a homologous chromosome if it is available for copying. If a cell retains DNA damage, transcription of a gene can be prevented and thus translation into a protein will also be blocked. Replication may also be blocked and/or the cell may die. Descriptions of reduced function, characteristic of aging and associated with accumulation of DNA damage, are given later in this article.

In contrast to DNA damage, a mutation is a change in the base sequence of the DNA. A mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation cannot be repaired. At the cellular level, mutations can cause alterations in protein function and regulation. Mutations are replicated when the cell replicates. In a population of cells, mutant cells will increase or decrease in frequency according to the effects of the mutation on the ability of the cell to survive and reproduce. Although distinctly different from each other, DNA damages and mutations are related because DNA damages often cause errors of DNA synthesis during replication or repair and these errors are a major source of mutation.

Given these properties of DNA damage and mutation, it can be seen that DNA damages are a special problem in non-dividing or slowly dividing cells, where unrepaired damages will tend to accumulate over time. On the other hand, in rapidly dividing cells, unrepaired DNA damages that do not kill the cell by blocking replication will tend to cause replication errors and thus mutation. The great majority of mutations that are not neutral in their effect are deleterious to a cell’s survival. Thus, in a population of cells comprising a tissue with replicating cells, mutant cells will tend to be lost. However, infrequent mutations that provide a survival advantage will tend to clonally expand at the expense of neighboring cells in the tissue. This advantage to the cell is disadvantageous to the whole organism, because such mutant cells can give rise to cancer. Thus DNA damages in frequently dividing cells, because they give rise to mutations, are a prominent cause of cancer. In contrast, DNA damages in infrequently dividing cells are likely a prominent cause of aging.

The first person to suggest that DNA damage, as distinct from mutation, is the primary cause of aging was Alexander in 1967. By the early 1980s there was significant experimental support for this idea in the literature. By the early 1990s experimental support for this idea was substantial, and furthermore it had become increasingly evident that oxidative DNA damage, in particular, is a major cause of aging.

In a series of articles from 1970 to 1977, PV Narasimh Acharya, Phd. (1924–1993) theorized and presented evidence that cells undergo "irreparable DNA damage," whereby DNA crosslinks occur when both normal cellular repair processes fail and cellular apoptosis does not occur. Specifically, Acharya noted that double-strand breaks and a "cross-linkage joining both strands at the same point is irreparable because neither strand can then serve as a template for repair. The cell will die in the next mitosis or in some rare instances, mutate."

Age-associated accumulation of DNA damage and decline in gene expression

In tissues composed of non- or infrequently replicating cells, DNA damage can accumulate with age and lead either to loss of cells, or, in surviving cells, loss of gene expression. Accumulated DNA damage is usually measured directly. Numerous studies of this type have indicated that oxidative damage to DNA is particularly important. The loss of expression of specific genes can be detected at both the mRNA level and protein level.

Brain

The adult brain is composed in large part of terminally differentiated non-dividing neurons. Many of the conspicuous features of aging reflect a decline in neuronal function. Accumulation of DNA damage with age in the mammalian brain has been reported during the period 1971 to 2008 in at least 29 studies. This DNA damage includes the oxidized nucleoside 8-oxo-2'-deoxyguanosine (8-oxo-dG), single- and double-strand breaks, DNA-protein crosslinks and malondialdehyde adducts (reviewed in Bernstein et al.). Increasing DNA damage with age has been reported in the brains of the mouse, rat, gerbil, rabbit, dog, and human.

Rutten et al. showed that single-strand breaks accumulate in the mouse brain with age. Young 4-day-old rats have about 3,000 single-strand breaks and 156 double-strand breaks per neuron, whereas in rats older than 2 years the level of damage increases to about 7,400 single-strand breaks and 600 double-strand breaks per neuron. Sen et al. showed that DNA damages which block the polymerase chain reaction in rat brain accumulate with age. Swain and Rao observed marked increases in several types of DNA damages in aging rat brain, including single-strand breaks, double-strand breaks and modified bases (8-OHdG and uracil). Wolf et al. also showed that the oxidative DNA damage 8-OHdG accumulates in rat brain with age. Similarly, it was shown that as humans age from 48–97 years, 8-OHdG accumulates in the brain.

Lu et al. studied the transcriptional profiles of the human frontal cortex of individuals ranging from 26 to 106 years of age. This led to the identification of a set of genes whose expression was altered after age 40. These genes play central roles in synaptic plasticity, vesicular transport and mitochondrial function. In the brain, promoters of genes with reduced expression have markedly increased DNA damage. In cultured human neurons, these gene promoters are selectively damaged by oxidative stress. Thus Lu et al. concluded that DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a program of brain aging that starts early in adult life.

Muscle

Muscle strength, and stamina for sustained physical effort, decline in function with age in humans and other species. Skeletal muscle is a tissue composed largely of multinucleated myofibers, elements that arise from the fusion of mononucleated myoblasts. Accumulation of DNA damage with age in mammalian muscle has been reported in at least 18 studies since 1971. We will mention here only two of the more recent studies in rodents plus one in humans. Hamilton et al. reported that the oxidative DNA damage 8-OHdG accumulates in heart and skeletal muscle (as well as in brain, kidney and liver) of both mouse and rat with age. In humans, increases in 8-OHdG with age were reported for skeletal muscle. Catalase is an enzyme that removes hydrogen peroxide, a reactive oxygen species, and thus limits oxidative DNA damage. In mice, when catalase expression is increased specifically in mitochondria, oxidative DNA damage (8-OHdG) in skeletal muscle is decreased and lifespan is increased by about 20%. These findings suggest that mitochondria are a significant source of the oxidative damages contributing to aging.

Protein synthesis and protein degradation decline with age in skeletal and heart muscle, as would be expected, since DNA damage blocks gene transcription. In a recent study Piec et al. found numerous changes in protein expression in rat skeletal muscle with age, including lower levels of several proteins related to myosin and actin. Force is generated in striated muscle by the interactions between myosin thick filaments and actin thin filaments.

Liver

Liver hepatocytes do not ordinarily divide and appear to be terminally differentiated, but they retain the ability to proliferate when injured. With age, the mass of the liver decreases, blood flow is reduced, metabolism is impaired, and alterations in microcirculation occur. At least 21 studies have reported an increase in DNA damage with age in liver. For instance, Helbock et al. estimated that the steady state level of oxidative DNA base alterations increased from 24,000 per cell in the liver of young rats to 66,000 per cell in the liver of old rats.

Kidney

In kidney, changes with age include reduction in both renal blood flow and glomerular filtration rate, and impairment in the ability to concentrate urine and to conserve sodium and water. DNA damages, particularly oxidative DNA damages, increase with age (at least 8 studies). For instance Hashimoto et al. showed that 8-OHdG accumulates in rat kidney DNA with age.

Long-lived stem cells

Tissue-specific stem cells produce differentiated cells through a series of increasingly more committed progenitor intermediates. In hematopoiesis (blood cell formation), the process begins with long-term hematopoietic stem cells that self-renew and also produce progeny cells that upon further replication go through a series of stages leading to differentiated cells without self-renewal capacity. In mice, deficiencies in DNA repair appear to limit the capacity of hematopoietic stem cells to proliferate and self-renew with age. Sharpless and Depinho reviewed evidence that hematopoietic stem cells, as well as stem cells in other tissues, undergo intrinsic aging. They speculated that stem cells grow old, in part, as a result of DNA damage. DNA damage may trigger signalling pathways, such as apoptosis, that contribute to depletion of stem cell stocks. This has been observed in several cases of accelerated aging and may occur in normal aging too.

A key aspect of hair loss with age is the aging of the hair follicle. Ordinarily, hair follicle renewal is maintained by the stem cells associated with each follicle. Aging of the hair follicle appears to be due to the DNA damage that accumulates in renewing stem cells during aging.

Mutation theories of aging

A popular idea, that has failed to gain significant experimental support, is the idea that mutation, as distinct from DNA damage, is the primary cause of aging. As discussed above, mutations tend to arise in frequently replicating cells as a result of errors of DNA synthesis when template DNA is damaged, and can give rise to cancer. However, in mice there is no increase in mutation in the brain with aging. Mice defective in a gene (Pms2) that ordinarily corrects base mispairs in DNA have about a 100-fold elevated mutation frequency in all tissues, but do not appear to age more rapidly. On the other hand, mice defective in one particular DNA repair pathway show clear premature aging, but do not have elevated mutation.

One variation of the idea that mutation is the basis of aging, that has received much attention, is that mutations specifically in mitochondrial DNA are the cause of aging. Several studies have shown that mutations accumulate in mitochondrial DNA in infrequently replicating cells with age. DNA polymerase gamma is the enzyme that replicates mitochondrial DNA. A mouse mutant with a defect in this DNA polymerase is only able to replicate its mitochondrial DNA inaccurately, so that it sustains a 500-fold higher mutation burden than normal mice. These mice showed no clear features of rapidly accelerated aging. Overall, the observations discussed in this section indicate that mutations are not the primary cause of aging.

Dietary restriction

In rodents, caloric restriction slows aging and extends lifespan. At least 4 studies have shown that caloric restriction reduces 8-OHdG damages in various organs of rodents. One of these studies showed that caloric restriction reduced accumulation of 8-OHdG with age in rat brain, heart and skeletal muscle, and in mouse brain, heart, kidney and liver. More recently, Wolf et al. showed that dietary restriction reduced accumulation of 8-OHdG with age in rat brain, heart, skeletal muscle, and liver. Thus reduction of oxidative DNA damage is associated with a slower rate of aging and increased lifespan.

Inherited defects that cause premature aging

If DNA damage is the underlying cause of aging, it would be expected that humans with inherited defects in the ability to repair DNA damages should age at a faster pace than persons without such a defect. Numerous examples of rare inherited conditions with DNA repair defects are known. Several of these show multiple striking features of premature aging, and others have fewer such features. Perhaps the most striking premature aging conditions are Werner syndrome (mean lifespan 47 years), Huchinson-Gilford Progeria (mean lifespan 13 years), and Cockayne syndrome (mean lifespan 13 years).

Werner syndrome is due to an inherited defect in an enzyme (a helicase and exonuclease) that acts in base excision repair of DNA (e.g. see Harrigan et al.^[48]).

Hutchinson-Guilford Progeria is due to a defect in Lamin A protein which forms a scaffolding within the cell nucleus to organize chromatin and is needed for repair of double-strand breaks in DNA. A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in the DNA repair processes of non-homologous end joining and homologous recombination. Mouse cells deficient for maturation of prelamin A show increased DNA damage and chromosome aberrations and are more sensitive to DNA damaging agents.

Cockayne Syndrome is due to a defect in a protein necessary for the repair process, transcription coupled nucleotide excision repair, which can remove damages, particularly oxidative DNA damages, that block transcription.

In addition to these three conditions, several other human syndromes, that also have defective DNA repair, show several features of premature aging. These include ataxia telangiectasia, Nijmegen breakage syndrome, some subgroups of xeroderma pigmentosum, trichothiodystrophy, Fanconi anemia, Bloom syndrome and Rothmund-Thomson syndrome.

Ku bound to DNA

In addition to human inherited syndromes, experimental mouse models with genetic defects in DNA repair show features of premature aging and reduced lifespan. In particular, mutant mice defective in Ku70, or Ku80, or double mutant mice deficient in both Ku70 and Ku80 exhibit early aging. The mean lifespans of the three mutant mouse strains were similar to each other, at about 37 weeks, compared to 108 weeks for the wild-type control. Six specific signs of aging were examined, and the three mutant mice were found to display the same aging signs as the control mice, but at a much earlier age. Cancer incidence was not increased in the mutant mice. Ku70 and Ku80 form the heterodimer Ku protein essential for the non-homologous end joining (NHEJ) pathway of DNA repair, active in repairing DNA double-strand breaks. This suggests an important role of NHEJ in longevity assurance.

Defects in DNA repair cause features of premature aging

Many authors have noted an association between defects in the DNA damage response and premature aging (see e.g.). If a DNA repair protein is deficient, unrepaired DNA damages tend to accumulate. Such accumulated DNA damages appear to cause features of premature aging (segmental progeria). Table 1 lists 18 DNA repair proteins which, when deficient, cause numerous features of premature aging.

Table 1. DNA repair proteins that, when deficient, cause features of accelerated aging (segmental progeria).

Protein	Pathway	Description
ATR	Nucleotide excision repair	deletion of ATR in adult mice leads to a number of disorders including hair loss and graying, kyphosis, osteoporosis, premature involution of the thymus, fibrosis of the heart and kidney and decreased spermatogenesis
DNA-PKcs	Non-homologous end joining	shorter lifespan, earlier onset of aging related pathologies; higher level of DNA damage persistence
ERCC1	Nucleotide excision repair, Interstrand cross link repair	deficient transcription coupled NER with time-dependent accumulation of transcription-blocking damages; mouse life span reduced from 2.5 years to 5 months; Ercc1−/− mice are leukopenic and thrombocytopenic, and there is extensive adipose transformation of the bone marrow, hallmark features of normal aging in mice
ERCC2 (XPD)	Nucleotide excision repair (also transcription as part of TFIIH)	some mutations in ERCC2 cause Cockayne syndrome in which patients have segmental progeria with reduced stature, mental retardation, cachexia (loss of subcutaneous fat tissue), sensorineural deafness, retinal degeneration, and calcification of the central nervous system; other mutations in ERCC2 cause trichothiodystrophy in which patients have segmental progeria with brittle hair, short stature, progressive cognitive impairment and abnormal face shape; still other mutations in ERCC2 cause xeroderma pigmentosum (without a progeroid syndrome) and with extreme sun-mediated skin cancer predisposition
ERCC4 (XPF)	Nucleotide excision repair, Interstrand cross link repair, Single-strand annealing, Microhomology-mediated end joining	mutations in ERCC4 cause symptoms of accelerated aging that affect the neurologic, hepatobiliary, musculoskeletal, and hematopoietic systems, and cause an old, wizened appearance, loss of subcutaneous fat, liver dysfunction, vision and hearing loss, renal insufficiency, muscle wasting, osteopenia, kyphosis and cerebral atrophy
ERCC5 (XPG)	Nucleotide excision repair, Homologous recombinational repair, Base excision repair	mice with deficient ERCC5 show loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months
ERCC6 (Cockayne syndrome B or CS-B)	Nucleotide excision repair [especially transcription coupled repair (TC-NER) and interstrand crosslink repair]	premature aging features with shorter life span and photosensitivity, deficient transcription coupled NER with accumulation of unrepaired DNA damages, also defective repair of oxidatively generated DNA damages including 8-oxoguanine, 5-hydroxycytosine and cyclopurines
ERCC8 (Cockayne syndrome A or CS-A)	Nucleotide excision repair [especially transcription coupled repair (TC-NER) and interstrand crosslink repair]	premature aging features with shorter life span and photosensitivity, deficient transcription coupled NER with accumulation of unrepaired DNA damages, also defective repair of oxidatively generated DNA damages including 8-oxoguanine, 5-hydroxycytosine and cyclopurines
GTF2H5 (TTDA)	Nucleotide excision repair	deficiency causes trichothiodystrophy (TTD) a premature-ageing and neuroectodermal disease; humans with GTF2H5 mutations have a partially inactivated protein with retarded repair of 6-4-photoproducts
Ku70	Non-homologous end joining	shorter lifespan, earlier onset of aging related pathologies; persistent foci of DNA double-strand break repair proteins
Ku80	Non-homologous end joining	shorter lifespan, earlier onset of aging related pathologies; defective repair of spontaneous DNA damage
Lamin A	Non-homologous end joining, Homologous recombination	increased DNA damage and chromosome aberrations; progeria; aspects of premature aging; altered expression of numerous DNA repair factors
NRMT1	Nucleotide excision repair	mutation in NRMT1 causes decreased body size, female-specific infertility, kyphosis, decreased mitochondrial function, and early-onset liver degeneration
RECQL4	Base excision repair, Nucleotide excision repair, Homologous recombination, Non-homologous end joining	mutations in RECQL4 cause Rothmund-Thomson syndrome, with alopecia, sparse eyebrows and lashes, cataracts and osteoporosis
SIRT6	Base excision repair, Nucleotide excision repair, Homologous recombination, Non-homologous end joining	SIRT6-deficient mice develop profound lymphopenia, loss of subcutaneous fat and lordokyphosis, and these defects overlap with aging-associated degenerative processes
SIRT7	Non-homologous end joining	mice defective in SIRT7 show phenotypic and molecular signs of accelerated aging such as premature pronounced curvature of the spine, reduced life span, and reduced non-homologous end joining
Werner syndrome helicase	Homologous recombination, Non-homologous end joining,Base excision repair,Replication arrest recovery	shorter lifespan, earlier onset of aging related pathologies, genome instability
ZMPSTE24	Homologous recombination	lack of Zmpste24 prevents lamin A formation and causes progeroid phenotypes in mice and humans, increased DNA damage and chromosome aberrations, sensitivity to DNA-damaging agents and deficiency in homologous recombination

Increased DNA repair and extended longevity

Table 2 lists DNA repair proteins whose increased expression is connected to extended longevity.

Table 2. DNA repair proteins that, when highly- or over-expressed, cause (or are associated with) extended longevity.

Protein	Pathway	Description
NDRG1	Direct reversal	long-lived Snell dwarf, GHRKO, and PAPPA-KO mice have increased expression of NDRG1; higher expression of NDRG1 can promote MGMT protein stability and enhanced DNA repair
NUDT1 (MTH1)	Oxidized nucleotide removal	degrades 8-oxodGTP; prevents the age-dependent accumulation of DNA 8-oxoguanine A transgenic mouse in which the human hMTH1 8-oxodGTPase is expressed, giving over-expression of hMTH1, increases the median lifespan of mice to 914 days vs. 790 days for wild-type mice. Mice with over-expressed hMTH1 have behavioral changes of reduced anxiety and enhanced investigation of environmental and social cues
PARP1	Base excision repair, Nucleotide excision repair, Microhomology-mediated end joining, Single-strand break repair	PARP1 activity in blood cells of thirteen mammalian species (rat, guinea pig, rabbit, marmoset, sheep, pig, cattle, pigmy chimpanzee, horse, donkey, gorilla, elephant and man) correlates with maximum lifespan of the species.
SIRT1	Nucleotide excision repair, Homologous recombination, Non-homologous end joining	Increased expression of SIRT1 in male mice extends the lifespan of mice fed a standard diet, accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density, and insulin sensitivity
SIRT6	Base excision repair, Nucleotide excision repair, Homologous recombination, Non-homologous end joining	male, but not female, transgenic mice overexpressing Sirt6 have a significantly longer lifespan than wild-type mice

Lifespan in different mammalian species

Studies comparing DNA repair capacity in different mammalian species have shown that repair capacity correlates with lifespan. The initial study of this type, by Hart and Setlow, showed that the ability of skin fibroblasts of seven mammalian species to perform DNA repair after exposure to a DNA damaging agent correlated with lifespan of the species. The species studied were shrew, mouse, rat, hamster, cow, elephant and human. This initial study stimulated many additional studies involving a wide variety of mammalian species, and the correlation between repair capacity and lifespan generally held up. In one of the more recent studies, Burkle et al. studied the level of a particular enzyme, Poly ADP ribose polymerase, which is involved in repair of single-strand breaks in DNA. They found that the lifespan of 13 mammalian species correlated with the activity of this enzyme.

The DNA repair transcriptomes of the liver of humans, naked mole-rats and mice were compared. The maximum lifespans of humans, naked mole-rat, and mouse are respectively ~120, 30 and 3 years. The longer-lived species, humans and naked mole rats expressed DNA repair genes, including core genes in several DNA repair pathways, at a higher level than did mice. In addition, several DNA repair pathways in humans and naked mole-rats were up-regulated compared with mouse. These findings suggest that increased DNA repair facilitates greater longevity.

Over the past decade, a series of papers have shown that the mitochondrial DNA (mtDNA) base composition correlates with animal species maximum life span. The mitochondrial DNA base composition is though to reflect its nucleotide-specific (guanine, cytosine, thymidine and adenine) different mutation rates (i.e., accumulation of guanine in the mitochondrial DNA of an animal species is due to low guanine mutation rate in the mitochondria of that species).

Centenarians

Lymphoblastoid cell lines established from blood samples of humans who lived past 100 years (centenarians) have significantly higher activity of the DNA repair protein Poly (ADP-ribose) polymerase (PARP) than cell lines from younger individuals (20 to 70 years old). 

The lymphocytic cells of centenarians have characteristics typical of cells from young people, both in their capability of priming the mechanism of repair after H₂O₂ sublethal oxidative DNA damage and in their PARP capacity.

Menopause

As women age, they experience a decline in reproductive performance leading to menopause. This decline is tied to a decline in the number of ovarian follicles. Although 6 to 7 million oocytes are present at mid-gestation in the human ovary, only about 500 (about 0.05%) of these ovulate, and the rest are lost. The decline in ovarian reserve appears to occur at an increasing rate with age, and leads to nearly complete exhaustion of the reserve by about age 51. As ovarian reserve and fertility decline with age, there is also a parallel increase in pregnancy failure and meiotic errors resulting in chromosomally abnormal conceptions.

Titus et al. have proposed an explanation for the decline in ovarian reserve with age. They showed that as women age, double-strand breaks accumulate in the DNA of their primordial follicles. Primordial follicles are immature primary oocytes surrounded by a single layer of granulosa cells. An enzyme system is present in oocytes that normally accurately repairs DNA double-strand breaks. This repair system is referred to as homologous recombinational repair, and it is especially active during meiosis. Titus et al. also showed that expression of four key DNA repair genes that are necessary for homologous recombinational repair (BRCA1, MRE11, Rad51 and ATM) decline in oocytes with age. This age-related decline in ability to repair double-strand damages can account for the accumulation of these damages, which then likely contributes to the decline in ovarian reserve.

Women with an inherited mutation in the DNA repair gene BRCA1 undergo menopause prematurely, suggesting that naturally occurring DNA damages in oocytes are repaired less efficiently in these women, and this inefficiency leads to early reproductive failure. Genomic data from about 70,000 women were analyzed to identify protein-coding variation associated with age at natural menopause. Pathway analyses identified a major association with DNA damage response genes, particularly those expressed during meiosis and including a common coding variant in the BRCA1 gene.

Atherosclerosis

The most important risk factor for cardiovascular problems is chronological aging. Several research groups have reviewed evidence for a key role of DNA damage in vascular aging.

Atherosclerotic plaque contains vascular smooth muscle cells, macrophages and endothelial cells and these have been found to accumulate 8-oxoG, a common type of oxidative DNA damage. DNA strand breaks also increased in atherosclerotic plaques, thus linking DNA damage to plaque formation.

Werner syndrome (WS), a premature aging condition in humans, is caused by a genetic defect in a RecQ helicase that is employed in several DNA repair processes. WS patients develop a substantial burden of atherosclerotic plaques in their coronary arteries and aorta. These findings link excessive unrepaired DNA damage to premature aging and early atherosclerotic plaque development.

DNA damage and the epigenetic clock

Endogenous, naturally occurring DNA damages are frequent, and in humans include an average of about 10,000 oxidative damages per day and 50 double-strand DNA breaks per cell cycle.

Several reviews summarize evidence that the methylation enzyme DNMT1 is recruited to sites of oxidative DNA damage. Recruitment of DNMT1 leads to DNA methylation at the promoters of genes to inhibit transcription during repair. In addition, the 2018 review describes recruitment of DNMT1 during repair of DNA double-strand breaks. DNMT1 localization results in increased DNA methylation near the site of recombinational repair, associated with altered expression of the repaired gene. In general, repair-associated hyper-methylated promoters are restored to their former methylation level after DNA repair is complete. However, these reviews also indicate that transient recruitment of epigenetic modifiers can occasionally result in subsequent stable epigenetic alterations and gene silencing after DNA repair has been completed.

In human and mouse DNA, cytosine followed by guanine (CpG) is the least frequent dinucleotide, making up less than 1% of all dinucleotides (see CG suppression). At most CpG sites cytosine is methylated to form 5-methylcytosine. As indicated in the article CpG site, in mammals, 70% to 80% of CpG cytosines are methylated. However, in vertebrates there are CpG islands, about 300 to 3,000 base pairs long, with interspersed DNA sequences that deviate significantly from the average genomic pattern by being CpG-rich. These CpG islands are predominantly nonmethylated. In humans, about 70% of promoters located near the transcription start site of a gene (proximal promoters) contain a CpG island (see CpG islands in promoters). If the initially nonmethylated CpG sites in a CpG island become largely methylated, this causes stable silencing of the associated gene.

For humans, after adulthood is reached and during subsequent aging, the majority of CpG sequences slowly lose methylation (called epigenetic drift). However, the CpG islands that control promoters tend to gain methylation with age. The gain of methylation at CpG islands in promoter regions is correlated with age, and has been used to create an epigenetic clock (see article Epigenetic clock).
There may be some relationship between the epigenetic clock and epigenetic alterations accumulating after DNA repair. Both unrepaired DNA damage accumulated with age and accumulated methylation of CpG islands would silence genes in which they occur, interfere with protein expression, and contribute to the aging phenotype.

Longevity

From Wikipedia, the free encyclopedia

Comparison of male and female life expectancy at birth for countries and territories as defined in the 2011 CIA Factbook, with selected bubbles labelled. The green dotted line corresponds to equal female and male life expectancy. The apparent 3D volumes of the bubbles are linearly proportional to their population

The word "longevity" is sometimes used as a synonym for "life expectancy" in demography. However, the term longevity is sometimes meant to refer only to especially long-lived members of a population, whereas life expectancy is always defined statistically as the average number of years remaining at a given age. For example, a population's life expectancy at birth is the same as the average age at death for all people born in the same year (in the case of cohorts). Longevity is best thought of as a term for general audiences meaning 'typical length of life' and specific statistical definitions should be clarified when necessary.

Reflections on longevity have usually gone beyond acknowledging the brevity of human life and have included thinking about methods to extend life. Longevity has been a topic not only for the scientific community but also for writers of travel, science fiction, and utopian novels.

There are many difficulties in authenticating the longest human life span ever by modern verification standards, owing to inaccurate or incomplete birth statistics. Fiction, legend, and folklore have proposed or claimed life spans in the past or future vastly longer than those verified by modern standards, and longevity narratives and unverified longevity claims frequently speak of their existence in the present.

A life annuity is a form of longevity insurance.

Life expectancy, as of 2010

Various factors contribute to an individual's longevity. Significant factors in life expectancy include gender, genetics, access to health care, hygiene, diet and nutrition, exercise, lifestyle, and crime rates. Below is a list of life expectancies in different types of countries:

• Developed countries: 77–90 years (e.g. Canada: 81.29 years, 2010 est.)
• Developing countries: 32–80 years (e.g. Mozambique: 41.37 years, 2010 est.)

Population longevities are increasing as life expectancies around the world grow:

• Australia: 80 years in 2002, 81.72 years in 2010
• France: 79.05 years in 2002, 81.09 years in 2010
• Germany: 77.78 years in 2002, 79.41 years in 2010
• Italy: 79.25 years in 2002, 80.33 years in 2010
• Japan: 81.56 years in 2002, 82.84 years in 2010
• Monaco: 79.12 years in 2002, 79.73 years in 2011
• Spain: 79.06 years in 2002, 81.07 years in 2010
• UK: 80 years in 2002, 81.73 years in 2010
• USA: 77.4 years in 2002, 78.24 years in 2010

Long-lived individuals

The Gerontology Research Group validates current longevity records by modern standards, and maintains a list of supercentenarians; many other unvalidated longevity claims exist. Record-holding individuals include:

• Eilif Philipsen (1682–1785, 102 years, 333 days): first person to reach the ages of 100, 101, and 102 (on July 21, 1782) and whose age could be validated.
• Geert Adriaans Boomgaard (1788–1899, 110 years, 135 days): first person to reach the age of 110 (on September 21, 1898) and whose age could be validated
• Margaret Ann Neve, (18 May 1792 – 4 April 1903, 110 years, 346 days) the first validated female supercentenarian (on 18 May 1902)
• Jeanne Calment (1875–1997, 122 years, 164 days): the oldest person in history whose age has been verified by modern documentation. This defines the modern human life span, which is set by the oldest documented individual who ever lived.
• Sarah Knauss (1880–1999, 119 years, 97 days): the second oldest documented person in modern times and the oldest American.
• Jiroemon Kimura (1897–2013, 116 years, 54 days): the oldest man in history whose age has been verified by modern documentation.

Major factors

Old man at a nursing home in Norway

Evidence-based studies indicate that longevity is based on two major factors, genetics and lifestyle choices.

Genetics

Twin studies have estimated that approximately 20-30% the variation in human lifespan can be related to genetics, with the rest due to individual behaviors and environmental factors which can be modified. Although over 200 gene variants have been associated with longevity according to a US-Belgian-UK research database of human genetic variants, these explain only a small fraction of the heritability. A 2012 study found that even modest amounts of leisure time physical exercise can extend life expectancy by as much as 4.5 years.

Lymphoblastoid cell lines established from blood samples of centenarians have significantly higher activity of the DNA repair protein PARP (Poly ADP ribose polymerase) than cell lines from younger (20 to 70 year old) individuals. The lymphocytic cells of centenarians have characteristics typical of cells from young people, both in their capability of priming the mechanism of repair after H₂O₂ sublethal oxidative DNA damage and in their PARP gene expression. These findings suggest that elevated PARP gene expression contributes to the longevity of centenarians, consistent with the DNA damage theory of aging.

Change over time

In preindustrial times, deaths at young and middle age were more common than they are today. This is not due to genetics, but because of environmental factors such as disease, accidents, and malnutrition, especially since the former were not generally treatable with pre-20th century medicine. Deaths from childbirth were common for women, and many children did not live past infancy. In addition, most people who did attain old age were likely to die quickly from the above-mentioned untreatable health problems. Despite this, we do find many examples of pre-20th century individuals attaining lifespans of 85 years or greater, including Benjamin Franklin, Thomas Jefferson, John Adams, Cato the Elder, Thomas Hobbes, Eric of Pomerania, Christopher Polhem, and Michelangelo. This was also true for poorer people like peasants or laborers. Genealogists will almost certainly find ancestors living to their 70s, 80s and even 90s several hundred years ago.

For example, an 1871 census in the UK (the first of its kind, but personal data from other censuses dates back to 1841 and numerical data back to 1801) found the average male life expectancy as being 44, but if infant mortality is subtracted, males who lived to adulthood averaged 75 years. The present life expectancy in the UK is 77 years for males and 81 for females, while the United States averages 74 for males and 80 for females.

Studies have shown that black American males have the shortest lifespans of any group of people in the US, averaging only 69 years (Asian-American females average the longest). This reflects overall poorer health and greater prevalence of heart disease, obesity, diabetes, and cancer among black American men.

The normal duration of life was estimated to be 65-67 years in ancient times, 68-71 years in the Middle Ages, and 72-74 years in the first half of the 19th century.

Women normally outlive men. Theories for this include smaller bodies (and thus less stress on the heart), a stronger immune system (since testosterone acts as an immunosuppressant), and less tendency to engage in physically dangerous activities.

There is debate as to whether the pursuit of longevity is a worthwhile health care goal. Bioethicist Ezekiel Emanuel, who is also one of the architects of ObamaCare, has argued that the pursuit of longevity via the compression of morbidity explanation is a "fantasy" and that longevity past age 75 should not be considered an end in itself. This has been challenged by neurosurgeon Miguel Faria, who states that life can be worthwhile in healthy old age, that the compression of morbidity is a real phenomenon, and that longevity should be pursued in association with quality of life. Faria has discussed how longevity in association with leading healthy lifestyles can lead to the postponement of senescence as well as happiness and wisdom in old age.

Limited longevity

All of the biological organisms have a limited longevity, and different species of animals and plants have different potentials of longevity. Misrepair-accumulation aging theory suggests that the potential of longevity of an organism is related to its structural complexity. Limited longevity is due to the limited structural complexity of the organism. If a species of organisms has too high structural complexity, most of its individuals would die before the reproduction age, and the species could not survive. This theory suggests that limited structural complexity and limited longevity are essential for the survival of a species.

Longevity myths

Longevity myths are traditions about long-lived people (generally supercentenarians), either as individuals or groups of people, and practices that have been believed to confer longevity, but for which scientific evidence does not support the ages claimed or the reasons for the claims. A comparison and contrast of "longevity in antiquity" (such as the Sumerian King List, the genealogies of Genesis, and the Persian Shahnameh) with "longevity in historical times" (common-era cases through twentieth-century news reports) is elaborated in detail in Lucian Boia's 2004 book Forever Young: A Cultural History of Longevity from Antiquity to the Present and other sources.

After the death of Juan Ponce de León, Gonzalo Fernández de Oviedo y Valdés wrote in Historia General y Natural de las Indias (1535) that Ponce de León was looking for the waters of Bimini to cure his aging. Traditions that have been believed to confer greater human longevity also include alchemy, such as that attributed to Nicolas Flamel. In the modern era, the Okinawa diet has some reputation of linkage to exceptionally high ages.

Longevity claims may be subcategorized into four groups: "In late life, very old people often tend to advance their ages at the rate of about 17 years per decade .... Several celebrated super-centenarians (over 110 years) are believed to have been double lives (father and son, relations with the same names or successive bearers of a title) .... A number of instances have been commercially sponsored, while a fourth category of recent claims are those made for political ends ...." The estimate of 17 years per decade was corroborated by the 1901 and 1911 British censuses. Time magazine considered that, by the Soviet Union, longevity had been elevated to a state-supported "Methuselah cult". Robert Ripley regularly reported supercentenarian claims in Ripley's Believe It or Not!, usually citing his own reputation as a fact-checker to claim reliability.

Future

The U.S. Census Bureau view on the future of longevity is that life expectancy in the United States will be in the mid-80s by 2050 (up from 77.85 in 2006) and will top out eventually in the low 90s, barring major scientific advances that can change the rate of human aging itself, as opposed to merely treating the effects of aging as is done today. The Census Bureau also predicted that the United States would have 5.3 million people aged over 100 in 2100. The United Nations has also made projections far out into the future, up to 2300, at which point it projects that life expectancies in most developed countries will be between 100 and 106 years and still rising, though more and more slowly than before. These projections also suggest that life expectancies in poor countries will still be less than those in rich countries in 2300, in some cases by as much as 20 years. The UN itself mentioned that gaps in life expectancy so far in the future may well not exist, especially since the exchange of technology between rich and poor countries and the industrialization and development of poor countries may cause their life expectancies to converge fully with those of rich countries long before that point, similarly to the way life expectancies between rich and poor countries have already been converging over the last 60 years as better medicine, technology, and living conditions became accessible to many people in poor countries. The UN has warned that these projections are uncertain, and cautions that any change or advancement in medical technology could invalidate such projections.

Recent increases in the rates of lifestyle diseases, such as obesity, diabetes, hypertension, and heart disease, may eventually slow or reverse this trend toward increasing life expectancy in the developed world, but have not yet done so. The average age of the US population is getting higher and these diseases show up in older people.

Jennifer Couzin-Frankel examined how much mortality from various causes would have to drop in order to boost life expectancy and concluded that most of the past increases in life expectancy occurred because of improved survival rates for young people. She states that it seems unlikely that life expectancy at birth will ever exceed 85 years. Michio Kaku argues that genetic engineering, nanotechnology and future breakthroughs will accelerate the rate of life expectancy increase indefinitely. Already genetic engineering has allowed the life expectancy of certain primates to be doubled, and for human skin cells in labs to divide and live indefinitely without becoming cancerous.

However, since 1840, record life expectancy has risen linearly for men and women, albeit more slowly for men. For women the increase has been almost three months per year, for men almost 2.7 months per year. In light of steady increase, without any sign of limitation, the suggestion that life expectancy will top out must be treated with caution. Scientists Oeppen and Vaupel observe that experts who assert that "life expectancy is approaching a ceiling ... have repeatedly been proven wrong." It is thought that life expectancy for women has increased more dramatically owing to the considerable advances in medicine related to childbirth.

Non-human biological longevity

Currently living:

• A 5,068-year-old member of the species Pinus longaeva: Oldest known currently living tree.
• Methuselah: 4,800-year-old bristlecone pine in the White Mountains of California, the second oldest currently living organism known.

Non-living:

• Possibly 250-million year-old bacteria, Bacillus permians, were revived from stasis after being found in sodium chloride crystals in a cavern in New Mexico. Russell Vreeland, and colleagues from West Chester University in Pennsylvania, reported on October 18, 2000 that they had revived the halobacteria after bathing them with a nutrient solution. If they had survived for 250 million years, they would be the oldest living organisms ever recorded. However, their findings date the crystal surrounding the bacteria, and DNA analysis suggests the bacteria themselves are likely to be less ancient.
• A bristlecone pine nicknamed "Prometheus", felled by a climate dynamics researcher in the Great Basin National Park in Nevada in 1964, found to be about 4,900 years old, is the longest-lived single organism known.
• The quahog clam (Arctica islandica) is exceptionally long-lived, with a maximum recorded age of 507 years, the longest of any animal. Other clams of the species have been recorded as living up to 374 years.
• Lamellibrachia luymesi, a deep-sea cold-seep tubeworm, is estimated to reach ages of over 250 years based on a model of its growth rates.
• Hanako was the longest-lived vertebrate ever recorded at 226 years.
• A bowhead whale killed in a hunt was found to be approximately 211 years old (possibly up to 245 years old), the longest-lived mammal known.
• Tu'i Malila, a radiated tortoise presented to the Tongan royal family by Captain Cook, lived for over 185 years. It is the oldest documented reptile. Adwaitya, an Aldabra Giant Tortoise, may have lived for up to 250 years.

Biological immortality

Certain exotic organisms do not seem to be subject to aging and can live indefinitely. Examples include Tardigrades and Hydras. That is not to say that these organisms cannot die, merely that they only die as a result of disease or injury rather than age-related deterioration (and that they are not subject to the Hayflick limit).

Old age

From Wikipedia, the free encyclopedia

An elderly woman at a Ringing Cedars' settlement in Russia

Old age refers to ages nearing or surpassing the life expectancy of human beings, and is thus the end of the human life cycle. Terms and euphemisms include old people, elderly (worldwide usage), seniors (American usage), senior citizens (British and American usages), older adults (in the social sciences), the elderly, and elders (in many cultures—including the cultures of aboriginal people).

Old people often have limited regenerative abilities and are more susceptible to disease, syndromes, injuries and sickness than younger adults. The organic process of ageing is called senescence, the medical study of the aging process is called gerontology, and the study of diseases that afflict the elderly is called geriatrics. The elderly also face other social issues around retirement, loneliness, and ageism.

Old age is not a definite biological stage, as the chronological age denoted as "old age" varies culturally and historically.

In 2011, the United Nations proposed a human rights convention that would specifically protect older persons.

Definitions

Old Woman Dozing by Nicolaes Maes (1656). Royal Museums of Fine Arts, Brussels

Definitions of old age include official definitions, sub-group definitions, and four dimensions as follows.

Official definitions

Old age comprises "the later part of life; the period of life after youth and middle age . . ., usually with reference to deterioration". At what age old age begins cannot be universally defined because it differs according to the context. The United Nations has agreed that 65+ years may be usually denoted as old age and this is the first attempt at an international definition of old age. However, for its study of old age in Africa, the World Health Organization (WHO) set 55 as the beginning of old age. At the same time, the WHO recognized that the developing world often defines old age, not by years, but by new roles, loss of previous roles, or inability to make active contributions to society.

Most developed Western countries set the age of 60 to 65 for retirement. Being 60–65 years old is usually a requirement for becoming eligible for senior social programs. However, various countries and societies consider the onset of old age as anywhere from the mid-40s to the 70s. The definitions of old age continue to change especially as life expectancy in developed countries has risen to beyond 80 years old. In October 2016, a paper published in the science journal Nature presented the conclusion that the maximum human lifespan is an average age of 115, with an absolute upper limit of 125 years. However, the authors' methods and conclusions drew criticism from the scientific community, who concluded that the study was flawed.

Sub-group definitions

Gerontologists have recognized the very different conditions that people experience as they grow older within the years defined as old age. In developed countries, most people in their 60s and early 70s are still fit, active, and able to care for themselves. However, after 75, they will become increasingly frail, a condition marked by serious mental and physical debilitation.

Therefore, rather than lumping together all people who have been defined as old, some gerontologists have recognized the diversity of old age by defining sub-groups. One study distinguishes the young old (60 to 69), the middle old (70 to 79), and the very old (80+). Another study's sub-grouping is young-old (65 to 74), middle-old (75–84), and oldest-old (85+). A third sub-grouping is "young old" (65–74), "old" (74–84), and "old-old" (85+). Delineating sub-groups in the 65+ population enables a more accurate portrayal of significant life changes.

Two British scholars, Paul Higgs and Chris Gilleard, have added a "fourth age" sub-group. In British English, the "third age" is "the period in life of active retirement, following middle age". Higgs and Gilleard describe the fourth age as "an arena of inactive, unhealthy, unproductive, and ultimately unsuccessful ageing".

Dimensions of old age

Key Concepts in Social Gerontology lists four dimensions: chronological, biological, psychological, and social. Wattis and Curran add a fifth dimension: developmental. Chronological age may differ considerably from a person's functional age. The distinguishing marks of old age normally occur in all five senses at different times and different rates for different persons. In addition to chronological age, people can be considered old because of the other dimensions of old age. For example, people may be considered old when they become grandparents or when they begin to do less or different work in retirement.

Senior citizen

Senior citizen is a common euphemism for an old person used in American English, and sometimes in British English. It implies that the person being referred to is retired. This in turn usually implies that the person is over the retirement age, which varies according to country. Synonyms include old age pensioner or pensioner in British English, and retiree and senior in American English. Some dictionaries describe widespread use of "senior citizen" for people over the age of 65.

When defined in an official context, senior citizen is often used for legal or policy-related reasons in determining who is eligible for certain benefits available to the age group.

It is used in general usage instead of traditional terms such as old person, old-age pensioner, or elderly as a courtesy and to signify continuing relevance of and respect for this population group as "citizens" of society, of senior rank.

The term was apparently coined in 1938 during a political campaign. Famed caricaturist Al Hirschfeld claimed on several occasion that his father Isaac Hirschfeld invented the term 'senior citizen'. It has come into widespread use in recent decades in legislation, commerce, and common speech. Especially in less formal contexts, it is often abbreviated as "senior(s)", which is also used as an adjective.

In commerce, some businesses offer customers of a certain age a "senior discount". The age at which these discounts are available varies between 55, 60, 62 or 65, and other criteria may also apply. Sometimes a special "senior discount card" or other proof of age needs to be obtained and produced to show entitlement.

Age qualifications

The age which qualifies for senior citizen status varies widely. In governmental contexts, it is usually associated with an age at which pensions or medical benefits for the elderly become available. In commercial contexts, where it may serve as a marketing device to attract customers, the age is often significantly lower.

In the United States, the standard retirement age is currently 66 (gradually increasing to 67).

In Canada, the OAS (Old Age Security) pension is available at 65 (the Conservative government of Stephen Harper had planned to gradually increase the age of eligibility to 67, starting in the years 2023–2029, although the Liberal government of Justin Trudeau is considering leaving it at 65), and the CPP (Canada Pension Plan) as early as age 60.

The AARP allows couples in which one spouse has reached the age of 50 to join, regardless of the age of the other spouse.

Marks of old age

The distinguishing characteristics of old age are both physical and mental. The marks of old age are so unlike the marks of middle age that legal scholar Richard Posner suggests that, as an individual transitions into old age, he/she can be thought of as different persons "time-sharing" the same identity.

These marks do not occur at the same chronological age for everyone. Also, they occur at different rates and order for different people. Marks of old age can easily vary between people of the same chronological age.

A basic mark of old age that affects both body and mind is "slowness of behavior". This "slowing down principle" finds a correlation between advancing age and slowness of reaction and physical and mental task performance. However, studies from Buffalo University and Northwestern University have shown that the elderly are a happier age group than their younger counterparts.

Physical marks of old age

Physical marks of old age include the following:

• Bone and joint. Old bones are marked by "thinning and shrinkage". This might result in a loss of height (about two inches (5 cm) by age 80), a stooping posture in many people, and a greater susceptibility to bone and joint diseases such as osteoarthritis and osteoporosis.
• Chronic diseases. Some older persons have at least one chronic condition and many have multiple conditions. In 2007–2009, the most frequently occurring conditions among older persons in the United States were uncontrolled hypertension (34%), diagnosed arthritis (50%), and heart disease (32%).
• Chronic mucus hypersecretion (CMH) "defined as coughing and bringing up sputum . . . is a common respiratory symptom in elderly persons."
• Dental problems. May have less saliva and less ability for oral hygiene in old age which increases the chance of tooth decay and infection.
• Digestive system. About 40% of the time, old age is marked by digestive disorders such as difficulty in swallowing, inability to eat enough and to absorb nutrition, constipation and bleeding.
• Essential Tremor (ET) is an uncontrollable shaking in a part of the upper body. It is more common in the elderly and symptoms worsen with age.
• Eyesight. Presbyopia can occur by age 50 and it hinders reading especially of small print in low lighting. Speed with which an individual reads and the ability to locate objects may also be impaired. By age 80, more than half of all Americans either have a cataract or have had cataract surgery.
• Falls. Old age spells risk for injury from falls that might not cause injury to a younger person. Every year, about one-third of those 65 years old and over half of those 80 years old fall. Falls are the leading cause of injury and death for old people.
• Gait change. Some aspects of gait normally change with old age. Gait velocity slows after age 70. Double stance time (i.e., time with both feet on the ground) also increases with age. Because of gait change, old people sometimes appear to be walking on ice.
• Hair usually becomes grayer and also might become thinner. As a rule of thumb, around age 50, about 50% of Europeans have 50% grey hair. Many men are affected by balding, and women enter menopause.
• Hearing. By age 75 and older, 48% of men and 37% of women encounter impairments in hearing. Of the 26.7 million people over age 50 with a hearing impairment, only one in seven uses a hearing aid. In the 70–79 age range, the incidence of partial hearing loss affecting communication rises to 65%, predominantly among low-income males.
• Hearts can become less efficient in old age with a resulting loss of stamina. In addition, atherosclerosis can constrict blood flow.
• Immune function. Less efficient immune function (Immunosenescence) is a mark of old age.
• Lungs might expand less well; thus, they provide less oxygen.
• Mobility impairment or loss. "Impairment in mobility affects 14% of those between 65 and 74, but half of those over 85." Loss of mobility is common in old people. This inability to get around has serious "social, psychological, and physical consequences".
• Pain afflicts old people at least 25% of the time, increasing with age up to 80% for those in nursing homes. Most pains are rheumatological or malignant.
• Sexuality remains important throughout the lifespan and the sexual expression of "typical, healthy older persons is a relatively neglected topic of research". Sexual attitudes and identity are established in early adulthood and change minimally over the course of a lifetime. However, sexual drive in both men and women may decrease as they age. That said, there is a growing body of research on people's sexual behaviours and desires in later life that challenges the "asexual" image of older adults. People aged 75–102 continue to experience sensuality and sexual pleasure. Other known sexual behaviours in older age groups include sexual thoughts, fantasies and erotic dreams, masturbation, oral sex, vaginal and anal intercourse.
• Skin loses elasticity, becomes drier, and more lined and wrinkled.
• Wounds and injuries take longer to heal.
• Wounds and injuries are more likely to leave permanent scars.
• Sleep trouble holds a chronic prevalence of over 50% in old age and results in daytime sleepiness. In a study of 9,000 persons with a mean age of 74, only 12% reported no sleep complaints. By age 65, deep sleep goes down to about 5%.
• Taste buds diminish so that by age 80 taste buds are down to 50% of normal. Food becomes less appealing and nutrition can suffer.
• Over the age of 85, thirst perception decreases, such that 41% of the elderly drink insufficiently.
• Urinary incontinence is often found in old age.
• Voice. In old age, vocal cords weaken and vibrate more slowly. This results in a weakened, breathy voice that is sometimes called an "old person's voice".

Mental marks of old age

Mental marks of old age include the following:

• Adaptable describes most people in their old age. Despite the stressfulness of old age, they are described as "agreeable" and "accepting". However, old age dependence induces feelings of incompetence and worthlessness in a minority.
• Caution marks old age. This antipathy toward "risk-taking" stems from the fact that old people have less to gain and more to lose by taking risks than younger people.
• Depressed mood. According to Cox, Abramson, Devine, and Hollon (2012), old age is a risk factor for depression caused by prejudice (i.e., "deprejudice"). When people are prejudiced against the elderly and then become old themselves, their anti-elderly prejudice turns inward, causing depression. "People with more negative age stereotypes will likely have higher rates of depression as they get older." Old age depression results in the over-65 population having the highest suicide rate.
• Fear of crime in old age, especially among the frail, sometimes weighs more heavily than concerns about finances or health and restricts what they do. The fear persists in spite of the fact that old people are victims of crime less often than younger people.
• Increasing fear of health loss.
• Mental disorders afflict about 15% of people aged 60+ according to estimates by the World Health Organization. Another survey taken in 15 countries reported that mental disorders of adults interfered with their daily activities more than physical problems.
• Reduced mental and cognitive ability may afflict old age. Memory loss is common in old age due to the decrease in speed of information being encoded, stored, and retrieved. It takes more time to learn the same amount of new information. Dementia is a general term for memory loss and other intellectual abilities serious enough to interfere with daily life. Its prevalence increases in old age from about 10% at age 65 to about 50% over age 85. Alzheimer's disease accounts for 50 to 80 percent of dementia cases. Demented behavior can include wandering, physical aggression, verbal outbursts, depression, and psychosis.
• Set in one's ways describes a mind set of old age. A study of over 400 distinguished men and women in old age found a "preference for the routine". Explanations include old age's toll on the "fluid intelligence" and the "more deeply entrenched" ways of the old.

Perceptions of old age

Old age from a middle-age perspective

Many books by middle-age writers depict their perceptions of old people. One writer notices the change in his parents: they move slowly, they have lost strength, they repeat stories, their minds wander, and they fret. Another writer sees her aged parents and is bewildered: they refuse to follow her advice, they are obsessed with the past, they avoid risk, they live at a "glacial pace".

Other writers treat the perceptions of middle-age people regarding their own old age. In her The Denial of Aging, Dr. Muriel R. Gillick, a baby boomer, accuses her contemporaries of believing that by proper exercise and diet they can avoid the scourges of old age and proceed from middle age to death. Studies find that many people in the 55–75 range can postpone morbidity by practicing healthy lifestyles. These discourses take part in a general idea of successful ageing. However, at about age 80, all people experience similar morbidity. Even with healthy lifestyles, most 85+ people will undergo extended "frailty and disability".

Old age from an old-age perspective

Early old age is a pleasant time; children are grown, retirement from work, time to pursue interests. Many people are also willing to get involved in community and activist organizations to promote their well-being. In contrast, perceptions of old age by writers 80+ years old (old age in the real meaning of the term) tend to be negative.

Georges Minois (Wikidata) writes that the first man to talk about his old age was an Egyptian scribe who lived 4,500 years ago. The scribe addressed God with a prayer of lament:

O Sovereign my Lord! Oldness has come; old age has descended. Feebleness has arrived; dotage is here anew. The heart sleeps wearily every day.

The eyes are weak, the ears are deaf, the strength is disappearing because of weariness of the heart and the mouth is silent and cannot speak.

The heart is forgetful and cannot recall yesterday. The bone suffers old age. Good is become evil. All taste is gone. What old age does to men is evil in every respect.

Minois comments that the scribe's "cry shows that nothing has changed in the drama of decrepitude between the age of the Pharaoh and the atomic age" and "expresses all the anguish of old people in the past and the present".

Lillian Rubin, active in her 80s as an author, sociologist, and psychotherapist, opens her book 60 on Up: The Truth about Aging in America with "getting old sucks. It always has, it always will." Dr. Rubin contrasts the "real old age" with the "rosy pictures" painted by middle-age writers.

Writing at the age of 87, Mary C. Morrison delineates the heroism required by old age: to live through the disintegration of one's own body or that of someone you love. Morrison concludes, "old age is not for the fainthearted." In the book Life Beyond 85 Years, the 150 interviewees had to cope with physical and mental debilitation and with losses of loved ones. One interviewee described living in old age as "pure hell".

Old age from society's perspective

Based on his survey of old age in history, Georges Minois concludes that "it is clear that always and everywhere youth has been preferred to old age." In western thought, "old age is an evil, an infirmity and a dreary time of preparation for death." Furthermore, death is often preferred over "decrepitude, because death means deliverance".

"The problem of the ambiguity of old age has . . . been with us since the stage of primitive society; it was both the source of wisdom and of infirmity, experience and decrepitude, of prestige and suffering."

In the Classical period of Greek and Roman cultures, old age was denigrated as a time of "decline and decrepitude". "Beauty and strength" were esteemed and old age was viewed as defiling and ugly. Old age was reckoned as one of the unanswerable "great mysteries" along with evil, pain, and suffering. "Decrepitude, which shrivels heroes, seemed worse than death."

The Medieval and Renaissance periods depicted old age as "cruel or weak".

Historical periods reveal a mixed picture of the "position and status" of old people, but there has never been a "golden age of aging". Studies have disproved the popular belief that in the past old people were venerated by society and cared for by their families. Veneration for and antagonism toward the aged have coexisted in complex relationships throughout history. "Old people were respected or despised, honoured or put to death according to circumstance."

In ancient times, although some strong and healthy people lived until they were over 70 most died before they were 50. The general understanding is that those who lived into their 40's were treated with respect and awe. In contrast, those who were frail were seen as a burden and ignored or in extreme cases killed. People were defined as "old" because of their inability to perform useful tasks rather than their years.

"The Olympians did not like old people." Their youth rebelled against the old, driving them off or killing them.

Although he was skeptical of the gods, Aristotle concurred in the dislike of old people. In his Ethics, he wrote that "old people are miserly; they do not acknowledge disinterested friendship; only seeking for what can satisfy their selfish needs."

The 16th-century Utopians, Thomas More and Antonio de Guevara, allowed no decrepit old people in their fictional lands.

For Thomas More, on the island of Utopia, when people are so old as to have "out-lived themselves" and are terminally ill, in pain, and a burden to everyone, the priests exhort them about choosing to die. The priests assure them that "they shall be happy after death." If they choose to die, they end their lives by starvation or by taking opium.

Antonio de Guevara's utopian nation "had a custom, not to live longer than sixty five years". At that age, they practiced self-immolation. Rather than condemn the practice, Bishop Guevara called it a "golden world" in which people "have overcome the natural appetite to desire to live".

In the Modern period, the "cultural status" of old people has declined in many cultures. Joan Erikson observed that "aged individuals are often ostracized, neglected, and overlooked; elders are seen no longer as bearers of wisdom but as embodiments of shame."

Research on age-related attitudes consistently finds that negative attitudes exceed positive attitudes toward old people because of their looks and behavior. In his study Aging and Old Age, Posner discovers "resentment and disdain of older people" in American society.

Harvard University's implicit-association test measures implicit "attitudes and beliefs" about Young vis a vis Old. Blind Spot: Hidden Biases of Good People, a book about the test, reports that 80% of Americans have an "automatic preference for the young over old" and that attitude is true worldwide. The young are "consistent in their negative attitude" toward the old. Ageism documents that Americans generally have "little tolerance for older persons and very few reservations about harboring negative attitudes" about them.

Despite its prevalence, ageism is seldom the subject of public discourse.

In 2014, a documentary film called The Age of Love used humor and poignant adventures of 30 seniors who attend a speed dating event for 70- to 90-year-olds, and discovered how the search for romance changes; or does not change; from a childhood sweetheart to older age.

Old age from simulated perspective

Simone de Beauvoir wrote that "there is one form of experience that belongs only to those that are old – that of old age itself." Nevertheless, simulations of old age attempt to help younger people gain some understanding.

Texas A&M University offers a plan for an "Aging Simulation" workshop. The workshop is adapted from Sensitizing People to the Processes of Aging. Some of the simulations follow:

• Sight: Wearing swimmer's goggles with black paper pasted to lens with only a small hole to simulate tunnel vision,
• Hearing: Use ear plugs to dull the sound of people talking.
• Touch: Wearing thick gloves, button a shirt or buckle a belt.
• Dexterity: With tape around several fingers, unscrew a jar lid.
• Mobility and Balance: Carry packages in one hand while using a walker.

The Macklin Intergenerational Institute conducts Xtreme Aging workshops, as depicted in The New York Times. A condensed version was presented on NBC's Today Show and is available online. One exercise was to lay out 3 sets of 5 slips of paper. On set #1, write your 5 most enjoyed activities; on set #2, write your 5 most valued possessions; on set #3, write your 5 most loved people. Then "lose" them one by one, trying to feel each loss, until you have lost them all as happens in old age.

Old age frailty

An image of an elderly man being guided by a young child accompanies William Blake's poem London, from his Songs of Innocence and Experience

Most people in the age range of 60–80 (the years of retirement and early old age), enjoy rich possibilities for a full life, but the condition of frailty distinguished by "bodily failure" and greater dependence becomes increasingly common after that. In the United States, hospital discharge data from 2003 to 2011 shows that injury was the most common reason for hospitalization among patients aged 65+.

Gerontologists note the lack of research regarding and the difficulty in defining frailty. However, they add that physicians recognize frailty when they see it.

A group of geriatricians proposed a general definition of frailty as "a physical state of increased vulnerability to stressors that results from decreased reserves and disregulation in multiple physiological systems".

Prevalence of frailty

Frailty is a common condition in later old age but different definitions of frailty produce diverse assessments of prevalence. One study placed the incidence of frailty for ages 65+ at 10.7%. Another study placed the incidence of frailty in age 65+ population at 22% for women and 15% for men. A Canadian study illustrated how frailty increases with age and calculated the prevalence for 65+ as 22.4% and for 85+ as 43.7%.

A worldwide study of "patterns of frailty" based on data from 20 nations found (a) a consistent correlation between frailty and age, (b) a higher frequency among women, and (c) more frailty in wealthier nations where greater support and medical care increases longevity.

In Norway, a 20-year longitudinal study of 400 people found that bodily failure and greater dependence became prevalent in the 80+ years. The study calls these years the "fourth age" or "old age in the real meaning of the term". Similarly, the "Berlin Aging Study" rated over-all functionality on four levels: good, medium, poor, and very poor. People in their 70s were mostly rated good. In the 80–90 year range, the four levels of functionality were divided equally. By the 90–100 year range, 60% would be considered frail because of very poor functionality and only 5% still possessed good functionality.

In the United States, the 85+ age group is the fastest growing, a group that is almost sure to face the "inevitable decrepitude" of survivors. (Frailty and decrepitude are synonyms.)

Markers of frailty

Three unique markers of frailty have been proposed: (a) loss of any notion of invincibility, (b) loss of ability to do things essential to one's care, and (c) loss of possibility for a subsequent life stage.

Old age survivors on-average deteriorate from agility in their 65–80s to a period of frailty preceding death. This deterioration is gradual for some and precipitous for others. Frailty is marked by an array of chronic physical and mental problems which means that frailty is not treatable as a specific disease. These problems coupled with increased dependency in the basic activities of daily living (ADLs) required for personal care add emotional problems: depression and anxiety. In sum, frailty has been depicted as a group of "complex issues," distinct but "causally interconnected," that often include "comorbid diseases", progressive weakness, stress, exhaustion, and depression.

Misconceptions of frail people

Johnson and Barer did a pioneering study of Life Beyond 85 Years by interviews over a six-year period. In talking with 85-year-olds and older, they found some popular conceptions about old age to be erroneous. Such erroneous conceptions include (1) people in old age have at least one family member for support, (2) old age well-being requires social activity, and (3) "successful adaptation" to age-related changes demands a continuity of self-concept. In their interviews, Johnson and Barer found that 24% of the 85+ had no face-to-face family relationships; many have outlived their families. Second, that contrary to popular notions, the interviews revealed that the reduced activity and socializing of the over-85s does not harm their well-being; they "welcome increased detachment". Third, rather than a continuity of self-concept, as the interviewees faced new situations they changed their "cognitive and emotional processes" and reconstituted their "self–representation".

Care and costs

The hand of an elderly person

Frail people require a high level of care. Medical advances have made it possible to "postpone death" for years. This added time costs many frail people "prolonged sickness, dependence, pain, and suffering".

According to a study by the Agency for Healthcare Research and Quality (AHRQ), the rate of emergency department visits was consistently highest among patients ages 85 years and older in 2006–2011 in the United States. Additionally, patients aged 65+ had the highest percentage of hospital stays for adults with multiple chronic conditions but the second highest percentage of hospital costs in 2003–2014.

These final years are also costly in economic terms. One out of every four Medicare dollars is spent on the frail in their last year of life in attempts to postpone death.

Medical treatments in the final days are not only economically costly, they are often unnecessary, even harmful. Nortin Hadler, M.D. warns against the tendency to medicalize and overtreat the frail. In her Choosing Medical Care in Old Age, Michael R. Gillick M.D. argues that appropriate medical treatment for the frail is not the same as for the robust. The frail are vulnerable to "being tipped over" by any physical stress put on the system such as medical interventions.

Death and frailty

Old age, death, and frailty are linked because approximately half the deaths in old age are preceded by months or years of frailty.

Older Adults' Views on Death is based on interviews with 109 people in the 70–90 age range, with a mean age of 80.7. Almost 20% of the people wanted to use whatever treatment that might postpone death. About the same number said that, given a terminal illness, they would choose assisted suicide. Roughly half chose doing nothing except live day by day until death comes naturally without medical or other intervention designed to prolong life. This choice was coupled with a desire to receive palliative care if needed.

About half of older adults suffer multimorbidity, that is, they have three or more chronic conditions. Medical advances have made it possible to "postpone death," but in many cases this postponement adds "prolonged sickness, dependence, pain, and suffering," a time that is costly in social, psychological, and economic terms.

The longitudinal interviews of 150 age 85+ people summarized in Life Beyond 85 Years found "progressive terminal decline" in the year prior to death: constant fatigue, much sleep, detachment from people, things, and activities, simplified lives. Most of the interviewees did not fear death; some would welcome it. One person said, "Living this long is pure hell." However, nearly everyone feared a long process of dying. Some wanted to die in their sleep; others wanted to die "on their feet".

The study of Older Adults' Views on Death found that the more frail people were, the more "pain, suffering, and struggles" they were enduring, the more likely they were to "accept and welcome" death as a release from their misery. Their fear about the process of dying was that it would prolong their distress. Besides being a release from misery, some saw death as a way to reunion with departed loved ones. Others saw death as a way to free their caretakers from the burden of their care.

Religiosity in old age

Generally speaking, old people have always been more religious than young people. At the same time, wide cultural variations exist.

In the United States, 90% of old age Hispanics view themselves as very, quite, or somewhat religious. The Pew Research Center's study of black and white old people found that 62% of those in ages 65–74 and 70% in ages 75+ asserted that religion was "very important" to them. For all 65+ people, more women (76%) than men (53%) and more blacks (87%) than whites (63%) consider religion "very important" to them. This compares to 54% in the 30–49 age range.

In a British 20-year longitudinal study, less than half of the old people surveyed said that religion was "very important" to them, and a quarter said they had become less religious in old age. The late-life rise in religiosity is stronger in Japan than in the United States, but in the Netherlands it is minimal.

In the practice of religion, a study of 60+ people found that 25% read the Bible every day and over 40% look at religious TV. Pew Research found that in the age 65+ range, 75% of whites and 87% of blacks pray daily.

Participation in organized religion is not a good indicator of religiosity because transportation and health problems often hinder participation.

Demographic changes

In the industrialized countries, life expectancy and, thus, the old age population have increased consistently over the last decades. In the United States the proportion of people aged 65 or older increased from 4% in 1900 to about 12% in 2000. In 1900, only about 3 million of the nation's citizens were 65 or older (out of 76 million total American citizens). By 2000, the number of senior citizens had increased to about 35 million (of 280 million US citizens). Population experts estimate that more than 50 million Americans—about 17 percent of the population—will be 65 or older in 2020. By 2050, it is projected that at least 400,000 Americans will be 100 or older.

The number of old people is growing around the world chiefly because of the post–World War II baby boom and increases in the provision and standards of health care. By 2050, 33% of the developed world's population and almost 20% of the less developed world's population will be over 60 years old.

The growing number of people living to their 80s and 90s in the developed world has strained public welfare systems and has also resulted in increased incidence of diseases like cancer and dementia that were rarely seen in premodern times. When the United States Social Security program was created, persons older than 65 numbered only around 5% of the population and the average life expectancy of a 65-year-old in 1936 was approximately 5 years, while in 2011 it could often range from 10 to 20 years. Other issues that can arise from an increasing population are growing demands for health care and an increase in demand for different types of services.

Of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die of age-related causes. In industrialized nations, the proportion is much higher, reaching 90%.

Psychosocial aspects

An elderly Khmer woman

According to Erik Erikson's "Stages of Psychosocial Development", the human personality is developed in a series of eight stages that take place from the time of birth and continue on throughout an individual's complete life. He characterises old age as a period of "Integrity vs. Despair", during which a person focuses on reflecting back on his life. Those who are unsuccessful during this phase will feel that their life has been wasted and will experience many regrets. The individual will be left with feelings of bitterness and despair. Those who feel proud of their accomplishments will feel a sense of integrity. Successfully completing this phase means looking back with few regrets and a general feeling of satisfaction. These individuals will attain wisdom, even when confronting death. Coping is a very important skill needed in the aging process to move forward with life and not be 'stuck' in the past. The way a person adapts and copes, reflects his aging process on a psycho-social level.

For people in their 80s and 90s, Joan Erikson added a ninth stage in The Life Cycle Completed: Extended Version. As she wrote, she added the ninth stage because the Integrity of the eighth stage imposes "a serious demand on the senses of elders" and the Wisdom of the eighth stage requires capacities that ninth stage elders "do not usually have".

Newman & Newman also proposed a ninth stage of life, Elderhood. Elderhood refers to those individuals who live past the life expectancy of their birth cohorts. There are two different types of people described in this stage of life. The "young old" are the healthy individuals who can function on their own without assistance and can complete their daily tasks independently. The "old old" are those who depend on specific services due to declining health or diseases. This period of life is characterized as a period of "immortality vs. extinction". Immortality is the belief that your life will go on past death, some examples are an afterlife or living on through one's family. Extinction refers to feeling as if life has no purpose.

Theories of old age

An elderly Somali woman

 

An elderly woman walks down a road

Social theories, or concepts, propose explanations for the distinctive relationships between old people and their societies.

One of the theories is the disengagement theory proposed in 1961. This theory proposes that in old age a mutual disengagement between people and their society occurs in anticipation of death. By becoming disengaged from work and family responsibilities, according to this concept, people are enabled to enjoy their old age without stress. This theory has been subjected to the criticism that old age disengagement is neither natural, inevitable, nor beneficial. Furthermore, disengaging from social ties in old age is not across the board: unsatisfactory ties are dropped and satisfying ones kept.

In opposition to the disengagement theory, the activity theory of old age argues that disengagement in old age occurs not by desire, but by the barriers to social engagement imposed by society. This theory has been faulted for not factoring in psychological changes that occur in old age as shown by reduced activity, even when available. It has also been found that happiness in old age is not proportional to activity.

According to the continuity theory, in spite of the inevitable differences imposed by their old age, most people try to maintain continuity in personhood, activities, and relationships with their younger days.

Socioemotional selectivity theory also depicts how people maintain continuity in old age. The focus of this theory is continuity sustained by social networks, albeit networks narrowed by choice and by circumstances. The choice is for more harmonious relationships. The circumstances are loss of relationships by death and distance.

Life expectancy

Life expectancy by nation at birth in the year 2011 ranged from 48 years to 82. Low values indicate high death rates for infants and children.

In most parts of the world women live, on average, longer than men; even so, the disparities vary between 12 years in Russia to no difference or higher life expectancy for men in countries such as Zimbabwe and Uganda.

The number of elderly persons worldwide began to surge in the second half of the 20th century. Up to that time (and still true in underdeveloped countries), five or less percent of the population was over 65. Few lived longer than their 70s and people who attained advanced age (i.e. their 80s) were rare enough to be a novelty and were revered as wise sages. The worldwide over-65 population in 1960 was one-third of the under 5 population. By 2013, the over-65 population had grown to equal the under 5 population. The over-65 population is projected to double the under five by 2050.

Before the surge in the over-65 population, accidents and disease claimed many people before they could attain old age, and health problems in those over 65 meant a quick death in most cases. If a person lived to an advanced age, it was due to genetic factors and/or a relatively easy lifestyle, since diseases of old age could not be treated before the 20th century.

In October 2016, scientists identified the maximum human lifespan at an average age of 115, with an absolute upper limit of 125 years. However, the concept of a maximum lifespan in humans is still widely debated among the scientific community.

Old age benefits

German chancellor Otto von Bismarck created the world's first comprehensive government social safety net in the 1880s, providing for old age pensions.

In the United States of America, and the United Kingdom, 65 (UK 60 for women) was traditionally the age of retirement with full old age benefits.

In 2003, the age at which a United States citizen became eligible for full Social Security benefits began to increase gradually, and will continue to do so until it reaches 67 in 2027. Full retirement age for Social Security benefits for people retiring in 2012 is age 66. In the United Kingdom, the state pension age for men and women will rise to 66 in 2020 with further increases scheduled after that."

Originally, the purpose of old age pensions was to prevent elderly persons from being reduced to beggary, which is still common in some underdeveloped countries, but growing life expectancies and older populations have brought into question the model under which pension systems were designed. By 1990, the United States was spending 30 per cent of its budget on the elderly, compared with 2 per cent on education. The dominant perception of the American old age population changed from "needy" and "worthy" to "powerful" and "greedy," old people getting more than their share of the nation's resources. However, in 2011, using a Supplemental Poverty Measure (SPM), the old age American poverty rate was measured as 15.9%.

Assistance: devices and personal

Old man at a nursing home in Norway

In the United States in 2008, 11 million people aged 65+ lived alone: 5 million or 22% of ages 65–74, 4 million or 34% of ages 75–84, and 2 million or 41% of ages 85+. The 2007 gender breakdown for all people 65+ was men 19% and women 39%.

Many new assistive devices made especially for the home have enabled more old people to care for themselves activities of daily living (ADL). Able Data lists 40,000 assistive technology products in 20 categories. Some examples of devices are a medical alert and safety system, shower seat (making it so the person does not get tired in the shower and fall), a bed cane (offering support to those with unsteadiness getting in and out of bed) and an ADL cuff (used with eating utensils for people with paralysis or hand weakness).

A Swedish study found that at age 76, 46% of the subjects used assistive devices. When they reached age 86, 69% used them. The subjects were ambivalent regarding the use of the assistive devices: as "enablers" or as "disablers". People who view assistive devices as enabling greater independence accept and use them. Those who see them as symbols of disability reject them. However, organizations like Love for the Elderly aim to combat such age-related prejudice by educating the public about the importance of appreciating growing older, while also providing services of kindness to elders in senior homes.

Even with assistive devices as of 2006, 8.5 million Americans needed personal assistance because of impaired basic activities of daily living required for personal care or impaired instrumental activities of daily living (IADL) required for independent living. Projections place this number at 21 million by 2030 when 40% of Americans over 70 will need assistance. There are many options for such long term care to those who require it. There is home care in which a family member, volunteer, or trained professional will aid the person in need and help with daily activities. Another option is community services which can provide the person with transportation, meal plans, or activities in senior centers. A third option is assisted living where 24-hour round-the-clock supervision is given with aid in eating, bathing, dressing, etc. A final option is a nursing home which provides professional nursing care.

Depictions in art

A scholarly literature has emerged, especially in Britain, showing historical trends in the visual depiction of old age.

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  Jan van Eyck, Virgin and Child with Canon van der Paele, c. 1434–36
  
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  Albrecht Dürer, Portrait of the Artist's Mother at the Age of 63, 1514
  
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  Titian, Self-Portrait c. 1567