Stellar population

From Wikipedia, the free encyclopedia

In 1944, Walter Baade categorized groups of stars within the Milky Way from their spectra. Two main divisions were defined as Population I and II, with another division known as Population III added in 1978^[1]. Often now simply abbreviated as either Pop I, II or III, these differences were later shown to be highly significant, dividing stars into classes by their chemical composition or metallicity, whose small proportion of stellar matter consists of the "heavier chemical elements" beyond the more common elements of hydrogen and helium.^[2][3] By coincidence, each population group definition has decreasing metal content and increasing age. Hence, the first stars in the universe (low metal content) were deemed Population III, and recent stars (high metallicity) are Population I.

Stellar populations

Observation of the spectra of stars has revealed that the metallicity of older stars have fewer heavy elements compared to the Sun. This immediately suggests that metallicity has evolved through the generations of stars by the process of stellar evolution. In current cosmological models, the matter created in the Big Bang was mostly hydrogen and helium, with only a very tiny fraction of light elements like lithium and beryllium. After this, when the universe cooled sufficiently, the first stars were born as extremely metal-poor Population III stars. Without metals, it is postulated that their stellar masses were hundreds of times that of the Sun. In turn, these massive stars evolved very quickly, and their nucleosynthetic processes quickly created the first 26 elements (up to iron in the periodic table).^[4]

Current theoretical stellar models show that most high-mass Population III stars quickly exhausted their fuel and exploded in extremely energetic pair-instability supernovae. Those explosions would have thoroughly dispersed their material, ejecting metals into the interstellar medium (ISM), to be incorporated into the later generations of stars. Their destruction suggests that no galactic high-mass Population III stars should be observable. However, some Population III stars might be seen in high-redshift galaxies whose light originated during the earlier history of the universe.^{[citation needed]} None have been discovered. Stars too massive to produce pair-instability supernovae would have collapsed into black holes through a process known as photodisintegration, but some matter may have escaped during this process in the form of relativistic jets, and this could have "sprayed" the first metals into the universe.^[5][6]

A rendering of Mu Arae, a metal-rich population I star.

It has been proposed that recent supernovae SN 2006gy and SN 2007bi may have been pair-instability supernovae in which such super-massive Population III stars exploded. It has been speculated that these stars could have formed relatively recently in dwarf galaxies containing primordial metal-free interstellar matter; past supernovae in these galaxies could have ejected their metal-rich contents at speeds high enough for them to escape the galaxy, keeping the metal content of the galaxy very low.^[7]

The oldest observed stars, known as Population II, have very low metallicities;^[8][9] as subsequent generations of stars were born they became more metal-enriched, as the gaseous clouds from which they formed received the metal-rich dust manufactured by previous generations. As those stars died, they returned metal-enriched material to the interstellar medium via planetary nebulae and supernovae, enriching further the nebulae out of which the newer stars formed. These youngest stars, including the Sun, therefore have the highest metal content, and are known as Population I stars.

Population I stars

Population I, or metal-rich stars, are young stars with the highest metallicity out of all three populations. The Earth's Sun is an example of a metal-rich star. These are common in the spiral arms of the Milky Way galaxy. Generally, the youngest stars, the extreme Population I, are found farther toward the center of a galaxy, and intermediate Population I stars are farther out. The Sun is an intermediate Population I star. Population I stars have regular elliptical orbits of the galactic centre, with a low relative velocity. It was hypothesized that the high metallicity of Population I stars makes them more likely to possess planetary systems than the other two populations, because planets, particularly terrestrial planets, are thought to be formed by the accretion of metals.^[10] However, observations of the Kepler data-set have found smaller planets around stars with a range of metallicities, while only larger, potential gas giant planets are concentrated around stars with relatively higher metallicity — a finding that has implications for theories of gas giant formation.^[11] Between the intermediate Population I and the Population II stars comes the intermediary disc population.

Population II stars

Population II, or metal-poor stars, are those with relatively little metal. The idea of a relatively small amount must be kept in perspective as even metal-rich astronomical objects contain low percentages of any element other than hydrogen or helium; metals constitute only a tiny percentage of the overall chemical makeup of the universe, even 13.8 billion years after the Big Bang. However, metal-poor objects are even more primitive. These objects are formed during an earlier time of the universe. Intermediate Population I stars are common in the bulge near the centre of our galaxy, whereas Population II stars found in the galactic halo are older and thus more metal-poor. Globular clusters also contain high numbers of population II stars.^[12] It is thought that population II stars created all the other elements in the periodic table, except the more unstable ones. An interesting characteristic of Population II stars is that despite their lower overall metallicity, they often have a higher ratio of alpha elements (O, Si, Ne, etc.) relative to Fe as compared to Population I stars; current theory suggests this is the result of Type II supernovae being more important contributors to the interstellar medium at the time of their formation, whereas Type Ia supernovae metal enrichment came later in the universe's evolution.^[13]

Scientists have targeted these oldest stars in several different surveys, including the HK objective-prism survey of Timothy C. Beers et al. and the Hamburg-ESO survey of Norbert Christlieb et al., originally started for faint quasars. Thus far, they have uncovered and studied in detail about ten very metal-poor stars (such as Sneden's Star, Cayrel's Star, BD +17° 3248) and three of the oldest stars known to date: HE0107-5240, HE1327-2326 and HE 1523-0901. Caffau's star was identified as the most metal-poor star yet when it was found in 2012 using Sloan Digital Sky Survey data. However, in February 2014 the discovery of an even lower metallicity star was announced, SMSS J031300.36-670839.3 located with the aid of SkyMapper astronomical survey data. Less extreme in their metal deficiency, but nearer and brighter and hence longer known, are HD 122563 (a red giant) and HD 140283 (a subgiant).

Population III stars

Possible glow of Population III stars imaged by NASA's Spitzer Space Telescope

Population III stars^[14] are a hypothetical population of extremely massive and hot stars with virtually no metals, except possibly for intermixing ejecta from other nearby Pop III supernovas. Their existence is inferred from physical cosmology, but they have not yet been observed directly. Indirect evidence for their existence has been found in a gravitationally lensed galaxy in a very distant part of the universe.^[15] Their existence may account for the fact that heavy elements—which could not have been created in the Big Bang—are observed in quasar emission spectra.^[4] They are also thought to be components of faint blue galaxies. These stars likely triggered the universe's period of reionization, a major phase transition of gases leading to the opacity observed today. Observations of the galaxy UDFy-38135539 suggest it may have played a role in this reionization process. Some theories hold that there were two generations of Pop III stars.^[16]

Artist's impression of the first stars, 400 million years after the Big Bang.

Current theory is divided on whether the first stars were very massive or not—theories proposed in 2009 and 2011 suggest the first star groups might have consisted of a massive star surrounded by several smaller stars.^[17][18][19] One theory, developed by computer models of star formation, is that with no heavy elements and a much warmer interstellar medium from the Big Bang, it was easy to form stars with much greater total mass than the ones visible today.^{[citation needed]} Typical masses for Pop  III stars are expected to be about several hundred solar masses, which is much larger than that of current stars. Analysis of data of extremely low-metallicity Population II stars such as HE0107-5240, which are thought to contain the metals produced by Population III stars, suggest that these metal-free stars had masses of 20 to 130 solar masses.^[20] On the other hand, analysis of globular clusters associated with elliptical galaxies suggests pair-instability supernovae, which are typically associated with very massive stars, were responsible for their metallic composition.^[21] This also explains why there have been no low-mass stars with zero metallicity observed, although models have been constructed for smaller Pop  III stars.^[22][23] Clusters containing zero-metallicity red dwarfs or brown dwarfs (possibly created by pair-instability supernovae^[9]) have been proposed as dark matter candidates,^[24][25] but searches for these and other MACHOs through gravitational microlensing have produced negative results.

Detection of Population III stars is a goal of NASA's James Webb Space Telescope.^[26] New spectroscopic surveys, such as SEGUE or SDSS-II, may also locate Pop III stars.^{[citation needed]} Stars observed in the Cosmos Redshift 7 galaxy at z = 6.60 may be Population III stars. Such stars are likely to have existed in the very early universe (i.e., at high redshift), and may have started the production of chemical elements heavier than hydrogen that are needed for the later formation of planets and life as we know it.^[27][28]

Faint young Sun paradox

From Wikipedia, the free encyclopedia

 

Artist's depiction of the life cycle of a Sun-like star, starting as a main-sequence star at lower left then expanding through the subgiant and giant phases, until its outer envelope is expelled to form a planetary nebula at upper right.

The faint young Sun paradox describes the apparent contradiction between observations of liquid water early in Earth's history and the astrophysical expectation that the Sun's output would be only 70 percent as intense during that epoch as it is during the modern epoch. The issue was raised by astronomers Carl Sagan and George Mullen in 1972.^[1] Explanations of this paradox have taken into account greenhouse effects, astrophysical influences, or a combination of the two.

The unresolved question is how a climate suitable for life was maintained on Earth over the long timescale despite the variable solar output and wide range of terrestrial conditions.^[2]

Early solar output

Early in Earth's history, the Sun's output would have been only 70 percent as intense as it is during the modern epoch. In the environmental conditions existing at that time, this solar output would have been insufficient to maintain a liquid ocean. Astronomers Carl Sagan and George Mullen pointed out in 1972 that this is contrary to the geological and paleontological evidence.^[1]

According to the Standard Solar Model, stars similar to the Sun should gradually brighten over their main sequence lifetime due to contraction of the stellar core caused by fusion.^[3] However, with the predicted solar luminosity 4 billion (4 × 10⁹) years ago and with greenhouse gas concentrations the same as are current for the modern Earth, any liquid water exposed to the surface would freeze. However, the geological record shows a continually relatively warm surface in the full early temperature record of Earth, with the exception of a cold phase, the Huronian glaciation, about 2.4 to 2.1 billion years ago. Water-related sediments have been found dating to as early as 3.8 billion years ago.^[4] Hints of early life forms have been dated from as early as 3.5 billion years,^[5] and the basic carbon isotopy is very much in line with what is found today.^[6] A regular alternation between ice ages and warm periods is only found occurring in the period since one billion years ago.^{[citation needed]}

Greenhouse hypothesis

When it first formed, Earth's atmosphere may have contained more greenhouse gases. Carbon dioxide concentrations may have been higher, with estimated partial pressure as large as 1,000 kPa (10 mbar), because there was no bacterial photosynthesis to convert the CO₂ gas to organic carbon and gaseous oxygen. Methane, a very active greenhouse gas that reacts with oxygen to produce carbon dioxide and water vapor, may have been more prevalent as well, with a mixing ratio of 10⁻⁴ (100 parts per million by volume).^[7][8]

Based on a study of geological sulfur isotopes, in 2009 a group of scientists including Yuichiro Ueno from the University of Tokyo proposed that carbonyl sulfide (OCS) was present in the Archean atmosphere. Carbonyl sulfide is an efficient greenhouse gas and the scientists estimate that the additional greenhouse effect would have been sufficient to prevent Earth from freezing over.^[9]

Based on an "analysis of nitrogen and argon isotopes in fluid inclusions trapped in 3.0- to 3.5-billion-year-old hydrothermal quartz" a 2013 paper concludes that "dinitrogen did not play a significant role in the thermal budget of the ancient Earth and that the Archean partial pressure of CO₂ was probably lower than 0.7 bar".^[10] Burgess, one of the authors states "The amount of nitrogen in the atmosphere was too low to enhance the greenhouse effect of carbon dioxide sufficiently to warm the planet. However, our results did give a higher than expected pressure reading for carbon dioxide – at odds with the estimates based on fossil soils – which could be high enough to counteract the effects of the faint young Sun and will require further investigation."^[11] Also, in 2012-2016 the research by S.M. Som, based on the analysis of raindrop impressions and air bubbles trapped in ancient lavas, have further indicated a low atmospheric pressure below 1.1 bar and probably as low as 0.23 bar during an epoch 2.7 bn years from present.^[12]

Following the initial accretion of the continents after about 1 billion years,^[13] geo-botanist Heinrich Walter and others contend that a non-biological version of the carbon cycle provided a negative temperature feedback. The carbon dioxide in the atmosphere dissolved in liquid water and combined with metal ions derived from silicate weathering to produce carbonates. During ice age periods, this part of the cycle would shut down. Volcanic carbon emissions would then restart a warming cycle due to the greenhouse effect.^[14][15]

According to the Snowball Earth hypothesis, there may have been a number of periods when Earth's oceans froze over completely. The most recent such period may have been about 630 million years ago.^[16] Afterwards, the Cambrian explosion of new multicellular life forms started.

Greater radiogenic heat

The radiogenic heat from the decay of 4 isotopes affecting Earth's internal heat budget over time: ⁴⁰K (yellow), ²³⁵U (red), ²³⁸U (green) and ²³²Th (violet). In the past the contribution from ⁴⁰K and ²³⁵U was much higher and thus the overall radiogenic heat output was higher.

In the past, the geothermal release of decay heat, emitted from the decay of the isotopes potassium-40, uranium-235 and uranium-238 was considerably greater than it is today.^[17] The figure to the right shows that the isotope ratio between uranium-238 and uranium-235 was also considerably different than it is today, with the ratio essentially equivalent to that of modern low-enriched uranium. Therefore, natural uranium ore bodies, if present, would have been capable of supporting natural nuclear fission reactors with common light water as its moderator. Any attempts to explain the paradox must therefore factor in both radiogenic contributions, both from decay heat and from any potential natural nuclear fission reactors.

The primary mechanism for Earth warming by radiogenic heat is not the direct heating (which contribute less than 0.1% to the total heat input even of early Earth) but rather the establishment of the high geothermal gradient of the crust, resulting in greater out-gassing rate and therefore the higher concentration of greenhouse gases in early Earth atmosphere. Additionally, a hotter deep crust would limit the water absorption by crustal minerals, resulting in a smaller amount of high-albedo land protruding from the early oceans, causing more solar energy to be absorbed.

Greater tidal heating

The Moon was much closer to Earth billions of years ago,^[18] and therefore produced considerably more tidal heating.^[19]

Alternatives

Phanerozoic Climate Change

A minority view, propounded by the Israeli-American physicist Nir Shaviv, uses climatological influences of solar wind, combined with a hypothesis of Danish physicist Henrik Svensmark for a cooling effect of cosmic rays, to explain the paradox.^[20] According to Shaviv, the early Sun had emitted a stronger solar wind that produced a protective effect against cosmic rays. In that early age, a moderate greenhouse effect comparable to today's would have been sufficient to explain an ice-free Earth. Evidence for a more active early Sun has been found in meteorites.^[21]

The temperature minimum around 2.4 billion years goes along with a cosmic ray flux modulation by a variable star formation rate in the Milky Way. The reduced solar impact later results in a stronger impact of cosmic ray flux (CRF), which is hypothesized to lead to a relationship with climatological variations.

An alternative model of solar evolution may explain the faint young Sun paradox. In this model, the early Sun underwent an extended period of higher solar wind output. This caused a mass loss from the Sun on the order of 5−10 percent over its lifetime, resulting in a more consistent level of solar luminosity (as the early Sun had more mass, resulting in more energy output than was predicted). In order to explain the warm conditions in the Archean era, this mass loss must have occurred over an interval of about one billion years. However, records of ion implantation from meteorites and lunar samples show that the elevated rate of solar wind flux only lasted for a period of 0.1 billion years. Observations of the young Sun-like star π¹ Ursae Majoris matches this rate of decline in the stellar wind output, suggesting that a higher mass loss rate can not by itself resolve the paradox.^[22]

Examination of Archaean sediments appears inconsistent with the hypothesis of high greenhouse concentrations. Instead, the moderate temperature range may be explained by a lower surface albedo brought about by less continental area and the "lack of biologically induced cloud condensation nuclei". This would have led to increased absorption of solar energy, thereby compensating for the lower solar output.^[23]

On Mars

Usually, the faint young Sun paradox is framed in terms of Earth's paleoclimate. However, the issue also appears in the context of the climate on ancient Mars, where apparently liquid water was present, in significant amounts (hydrological cycle, lakes, rivers, rain, possibly seas and oceans), billions of years ago. Subsequently, significant liquid water disappeared from the surface of Mars. Presently, the surface of Mars is cold and dry. The variable solar output, assuming nothing else changed, would imply colder (and drier) conditions on Mars in the ancient past than they are today, apparently contrary to the empirical evidence from Mars exploration that suggest the wetter and milder past. An explanation of the faint young Sun paradox that could simultaneously account for the observations might be that the sun shed mass through the solar wind, though sufficient rate of mass shedding is so far unsupported by stellar observations and models.^[24]

An alternative possible explanation posits intermittent bursts of powerful greenhouse gases, like methane. Carbon dioxide alone, even at a pressure far higher than the current one, cannot explain temperatures required for presence of liquid water on early Mars.^[25]

Senescence

From Wikipedia, the free encyclopedia

An elderly man at a nursing home in Norway

Senescence (/sɪˈnɛsəns/) or biological aging (also spelled biological aging) is the gradual deterioration of function characteristic of most complex lifeforms, arguably found in all biological kingdoms, that on the level of the organism increases mortality after maturation. The word senescence can refer either to cellular senescence or to senescence of the whole organism. It is commonly believed that cellular senescence underlies organismal senescence. The science of biological aging is biogerontology.

Senescence is not the inevitable fate of all organisms and can be delayed. The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats, and the existence of species having negligible senescence and potentially immortal species such as Hydra, have motivated research into delaying and preventing senescence and thus age-related diseases. Organisms of some taxonomic groups, including some animals, experience chronological decrease in mortality, for all or part of their life cycle.^[1] On the other extreme are accelerated aging diseases, rare in humans. There is also the extremely rare and poorly understood "Syndrome X," whereby a person remains physically and mentally an infant or child throughout one's life.^[2][3]

Even if environmental factors do not cause aging, they may affect it; in such a way, for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of the body may age at different rates. Two organisms of the same species can also age at different rates, so that biological aging and chronological aging are quite distinct concepts.

Albeit indirectly, senescence is by far the leading cause of death (other than in the trivially accurate sense that cerebral hypoxia, i.e., lack of oxygen to the brain, is the immediate cause of all human death). 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, moreover, the proportion is much higher, reaching 90%.^[4]

There are a number of hypotheses as to why senescence occurs; for example, some posit it is programmed by gene expression changes, others that it is the cumulative damage caused by biological processes. Whether senescence as a biological process itself can be slowed down, halted or even reversed, is a subject of current scientific speculation and research.^[5]

Cellular senescence or cellular aging

Cellular senescence
(upper) Primary mouse embryonic fibroblast cells (MEFs) before senescence. Spindle-shaped. (lower) MEFs became senescent after passages. Cells grow larger, flatten shape and expressed senescence-associated β-galactosidase (SABG, blue areas), a marker of cellular senescence.

Cellular senescence is the phenomenon by which normal diploid cells cease to divide. In culture, fibroblasts can reach a maximum of 50 cell divisions before becoming senescent. This phenomenon is known as "replicative senescence", or the Hayflick limit.^[6] Replicative senescence is the result of telomere shortening that ultimately triggers a DNA damage response. Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes and cell-cell fusion, independent of telomere length. As such, cellular senescence represents a change in "cell state" rather than a cell becoming "aged" as the name confusingly suggests.

Although senescent cells can no longer replicate, they remain metabolically active and commonly adopt an immunogenic phenotype consisting of a pro-inflammatory secretome, the up-regulation of immune ligands, a pro-survival response, promiscuous gene expression (pGE) and stain positive for senescence-associated β-galactosidase activity.^[7] The nucleus of senescent cells is characterized by senescence-associated heterochromatin foci (SAHF) and DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS).^[8] Senescent cells affect tumour suppression, wound healing and possibly embryonic/placental development and a pathological role in age-related diseases.^[9]

The experimental elimination of senescent cells from transgenic progeroid mice^[10] and non-progeroid, naturally-aged mice^[11][12][13] led to greater resistance against aging-associated diseases.
Ectopic expression of the embryonic transcription factor, NANOG, is shown to reverse senescence and restore the proliferation and differentiation potential of senescent stem cells.^{[14][15][16][17][18]}

Epigenetic clock analysis of cellular senescence

According to a molecular biomarker of aging known as epigenetic clock,^[19] the three major types of cellular senescence, namely replicative senescence, oncogene-induced senescence and DNA damage-induced senescence are distinct because induction of replicative senescence (RS) and oncogene-induced senescence (OIS) were found to be accompanied by epigenetic aging of primary cells but senescence induced by DNA damage was not, even though RS and OIS activate the cellular DNA damage response pathway.^[20] These results highlight the independence of cellular senescence from epigenetic aging. Consistent with this, telomerase-immortalised cells continued to age (according to the epigenetic clock) without having been treated with any senescence inducers or DNA-damaging agents, re-affirming the independence of the process of epigenetic ageing from telomeres, cellular senescence, and the DNA damage response pathway. Although the uncoupling of senescence from cellular aging appears at first sight to be inconsistent with the fact that senescent cells contribute to the physical manifestation of organism ageing, as demonstrated by Baker et al., where removal of senescent cells slowed down aging.^[10] However, the epigenetic clock analysis of senescence suggests that cellular senescence is a state that cells are forced into as a result of external pressures such as DNA damage, ectopic oncogene expression and exhaustive proliferation of cells to replenish those eliminated by external/environmental factors.^[20] These senescent cells, in sufficient numbers, will undoubtedly cause the deterioration of tissues, which is interpreted as organism ageing. However, at the cellular level, aging, as measured by the epigenetic clock, is distinct from senescence. It is an intrinsic mechanism that exists from the birth of the cell and continues. This implies that if cells are not shunted into senescence by the external pressures described above, they would still continue to age. This is consistent with the fact that mice with naturally long telomeres still age and eventually die even though their telomere lengths are far longer than the critical limit, and they age prematurely when their telomeres are forcibly shortened, due to replicative senescence. Hence senescence is a route by which cells exit prematurely from the natural course of cellular ageing.^[20]

Aging of the whole organism

Organismal senescence is the aging of whole organisms. In general, aging is characterized by the declining ability to respond to stress, increased homeostatic imbalance, and increased risk of aging-associated diseases. Death is the ultimate consequence of aging, though "old age" is not a scientifically recognized cause of death because there is always a specific proximal cause, such as cancer, heart disease, or liver failure. Aging of whole organisms is therefore a complex process that can be defined as "a progressive deterioration of physiological function, an intrinsic age-related process of loss of viability and increase in vulnerability."^[21]

Differences in maximum life span among species correspond to different "rates of aging." For example, inherited differences in the rate of aging make a mouse elderly at 3 years and a human elderly at 80 years.^[22] These genetic differences affect a variety of physiological processes, including the efficiency of DNA repair, antioxidant enzymes, and rates of free radical production.

Supercentenarian Ann Pouder (8 April 1807 – 10 July 1917) photographed on her 110th birthday. A heavily lined face is common in human senescence.

Senescence of the organism gives rise to the Gompertz–Makeham law of mortality, which says that mortality rate accelerates rapidly with age.

Some animals, such as some reptiles and fish, age slowly (negligible senescence) and exhibit very long lifespans. Some even exhibit "negative senescence", in which mortality falls with age, in disagreement with the Gompertz–Makeham "law".^[1]

Whether replicative senescence (Hayflick limit) plays a causative role in organismal aging is at present an active area of investigation.

The oft-quoted evolutionary theorist George Williams wrote, "It is remarkable that after a seemingly miraculous feat of morphogenesis, a complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed."^[23]

There is a current debate as to whether or not the pursuit of longevity and the postponement of senescence are cost-effective health care goals given finite health care resources. Because of the accumulated infirmities of old age, bioethicist Ezekiel Emanuel, opines that the pursuit of longevity via the compression of morbidity hypothesis is a "fantasy" and that human life is not worth living after age 75; longevity then should not be a goal of health care policy.^[24] This opinion has been contested by neurosurgeon and medical ethicist Miguel Faria, who states that life can be worthwhile during old age, and that longevity should be pursued in association with the attainment of quality of life.^[25] Faria claims that postponement of senescence as well as happiness and wisdom can be attained in old age in a large proportion of those who lead healthy lifestyles and remain intellectually active.^[26]

Theories of aging

The exact etiology of senescence is still largely unclear and yet to be discovered. The process of senescence is complex, and may derive from a variety of different mechanisms and exist for a variety of different reasons. However, senescence is not universal. In a few simple species, such as those in the genus Hydra, senescence is negligible and cannot be detected.

Another related mechanism is that of the biologically immortal planarian flatworms, which have "apparently limitless [telomere] regenerative capacity fueled by a population of highly proliferative adult stem cells."^[27] These organisms are biologically immortal but not immortal in the traditional sense as they are nonetheless susceptible to trauma and infectious and non-infectious disease. Moreover, average lifespans can vary greatly within and between species. This suggests that both genetic and environmental factors contribute to aging.

In general, theories that explain senescence have been divided between the programmed and stochastic theories of aging. Programmed theories imply that aging is regulated by biological clocks operating throughout the lifespan. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair, and defense responses. The reproductive-cell cycle theory suggests that aging is caused by changes in hormonal signaling over the lifespan.^[28] Stochastic theories blame environmental impacts on living organisms that induce cumulative damage at various levels as the cause of aging, examples of which ranging from damage to DNA, damage to tissues and cells by oxygen radicals (widely known as free radicals countered by the even more well-known antioxidants), and cross-linking.

However, aging is seen as a progressive failure of homeodynamics–systemic preservation of homeostasis, involving genes for maintenance and repair, stochastic events leading to molecular damage and molecular heterogeneity, and chance events determining the probability of death. Since complex and interacting systems of maintenance and repair comprise the homeodynamic space of a biological system, aging is considered to be a progressive shrinkage of homeodynamic space mainly due to increased molecular heterogeneity.^{[citation needed]} In 2013, a group of scientists defined nine hallmarks of aging that are common between organisms with emphasis on mammals: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.^[29]

Evolutionary theories

A gene can be expressed at various stages of life. Therefore, natural selection can support lethal and harmful alleles, if their expression occurs after reproduction. Senescence may be the product of such selection.^[30][31][32] In addition, ageing is believed to have evolved because of the increasingly smaller probability of an organism still being alive at older age, due to predation and accidents, both of which may be random and age-invariant. The antagonistic plietropy theory states that strategies which result in a higher reproductive rate at a young age, but shorter overall lifespan, result in a higher lifetime reproductive success and are therefore favoured by natural selection. In essence, aging is, therefore, the result of investing resources in reproduction, rather than maintenance of the body (the "Disposable Soma" theory^[33]), in light of the fact that accidents, predation, and disease kill organisms regardless of how much energy is devoted to repair of the body. Various other theories of aging exist, and are not necessarily mutually exclusive.
The geneticist J. B. S. Haldane wondered why the dominant mutation that causes Huntington's disease remained in the population, and why natural selection had not eliminated it. The onset of this neurological disease is (on average) at age 45 and is invariably fatal within 10–20 years. Haldane assumed that, in human prehistory, few survived until age 45. Since few were alive at older ages and their contribution to the next generation was therefore small relative to the large cohorts of younger age groups, the force of selection against such late-acting deleterious mutations was correspondingly small. However, if a mutation affected younger individuals, selection against it would be strong. Therefore, late-acting deleterious mutations could accumulate in populations over evolutionary time through genetic drift, which has been demonstrated experimentally. This concept of higher accumulation of deleterious mutations for older organisms came to be known as the selection shadow.^[34]

Peter Medawar formalised this observation in his mutation accumulation theory of aging.^[35][36] "The force of natural selection weakens with increasing age—even in a theoretically immortal population, provided only that it is exposed to real hazards of mortality. If a genetic disaster... happens late enough in individual life, its consequences may be completely unimportant". The 'real hazards of mortality' are, in typical circumstances, predation, disease, and accidents. So, even an immortal population, whose fertility does not decline with time, will have fewer individuals alive in older age groups. This is called 'extrinsic mortality'. Young cohorts, not depleted in numbers yet by extrinsic mortality, contribute far more to the next generation than the few remaining older cohorts, so the force of selection against late-acting deleterious mutations, which affect only these few older individuals, is very weak. The mutations may not be selected against, therefore, and may spread over evolutionary time into the population.

The major testable prediction made by this model is that species that have high extrinsic mortality in nature will age more quickly and have shorter intrinsic lifespans. This is borne out among mammals, the best-studied in terms of life history. There is a correlation among mammals between body size and lifespan, such that larger species live longer than smaller species under controlled/optimum conditions, but there are notable exceptions. For instance, many bats and rodents are of similar size, yet bats live much longer. For instance, the little brown bat, half the size of a mouse, can live 30 years in the wild. A mouse will only live 2–3 years even under optimum conditions. The explanation is that bats have fewer predators, and therefore low extrinsic mortality. More individuals survive to later ages, so the force of selection against late-acting deleterious mutations is stronger. Fewer late-acting deleterious mutations equates to slower aging and therefore a longer lifespan. Birds are also warm-blooded and are similar in size to many small mammals, yet often live 5–10 times as long. They have less predation pressure than ground-dwelling mammals. Seabirds, which, in general, have the fewest predators of all birds, live longest.

When examining the body-size vs. lifespan relationship, one also observes that predatory mammals tend to live longer than prey mammals in a controlled environment, such as a zoo or nature reserve. The explanation for the long lifespans of primates (such as humans, monkeys, and apes) relative to body size is that their intelligence, and often their sociality, help them avoid becoming prey. High position in the food chain, intelligence and cooperativeness all reduce extrinsic mortality in species.

Another evolutionary theory of aging was proposed by George C. Williams^[37] and involves antagonistic pleiotropy. A single gene may affect multiple traits. Some traits that increase fitness early in life may also have negative effects later in life. But, because many more individuals are alive at young ages than at old ages, even small positive effects early can be strongly selected for, and large negative effects later may be very weakly selected against. Williams suggested the following example: Perhaps a gene codes for calcium deposition in bones, which promotes juvenile survival and will therefore be favored by natural selection; however, this same gene promotes calcium deposition in the arteries, causing negative atherosclerotic effects in old age. Thus, harmful biological changes in old age may result from selection for pleiotropic genes that are beneficial early in life but harmful later on. In this case, selection pressure is relatively high when Fisher's reproductive value is high and relatively low when Fisher's reproductive value is low.

Gene regulation

A number of genetic components of aging have been identified using model organisms, ranging from the simple budding yeast Saccharomyces cerevisiae to worms such as Caenorhabditis elegans and fruit flies (Drosophila melanogaster). Study of these organisms has revealed the presence of at least two conserved aging pathways.
One of these pathways involves the gene Sir2, a NAD+-dependent histone deacetylase. In yeast, Sir2 is required for genomic silencing at three loci: the yeast mating loci, the telomeres and the ribosomal DNA (rDNA). In some species of yeast, replicative aging may be partially caused by homologous recombination between rDNA repeats; excision of rDNA repeats results in the formation of extrachromosomal rDNA circles (ERCs). These ERCs replicate and preferentially segregate to the mother cell during cell division, and are believed to result in cellular senescence by titrating away (competing for) essential nuclear factors. ERCs have not been observed in other species (nor even all strains of the same yeast species) of yeast (which also display replicative senescence), and ERCs are not believed to contribute to aging in higher organisms such as humans (they have not been shown to accumulate in mammals in a similar manner to yeast). Extrachromosomal circular DNA (eccDNA) has been found in worms, flies, and humans. The origin and role of eccDNA in aging, if any, is unknown.

Despite the lack of a connection between circular DNA and aging in higher organisms, extra copies of Sir2 are capable of extending the lifespan of both worms and flies (though, in flies, this finding has not been replicated by other investigators, and the activator of Sir2 resveratrol does not reproducibly increase lifespan in either species.^[38]) Whether the Sir2 homologues in higher organisms have any role in lifespan is unclear, but the human SIRT1 protein has been demonstrated to deacetylate p53, Ku70, and the forkhead family of transcription factors. SIRT1 can also regulate acetylates such as CBP/p300, and has been shown to deacetylate specific histone residues.

RAS1 and RAS2 also affect aging in yeast and have a human homologue. RAS2 overexpression has been shown to extend lifespan in yeast.

Other genes regulate aging in yeast by increasing the resistance to oxidative stress. Superoxide dismutase, a protein that protects against the effects of mitochondrial free radicals, can extend yeast lifespan in stationary phase when overexpressed.

In higher organisms, aging is likely to be regulated in part through the insulin/IGF-1 pathway. Mutations that affect insulin-like signaling in worms, flies, and the growth hormone/IGF1 axis in mice are associated with extended lifespan. In yeast, Sir2 activity is regulated by the nicotinamidase PNC1. PNC1 is transcriptionally upregulated under stressful conditions such as caloric restriction, heat shock, and osmotic shock. By converting nicotinamide to niacin, nicotinamide is removed, inhibiting the activity of Sir2. A nicotinamidase found in humans, known as PBEF, may serve a similar function, and a secreted form of PBEF known as visfatin may help to regulate serum insulin levels. It is not known, however, whether these mechanisms also exist in humans, since there are obvious differences in biology between humans and model organisms.

Sir2 activity has been shown to increase under calorie restriction. Due to the lack of available glucose in the cells, more NAD+ is available and can activate Sir2. Resveratrol, a stilbenoid found in the skin of red grapes, was reported to extend the lifespan of yeast, worms, and flies (the lifespan extension in flies and worms have proved to be irreproducible by independent investigators^[38]). It has been shown to activate Sir2 and therefore mimics the effects of calorie restriction, if one accepts that caloric restriction is indeed dependent on Sir2.

Gene expression is imperfectly controlled, and it is possible that random fluctuations in the expression levels of many genes contribute to the aging process as suggested by a study of such genes in yeast.^[39] Individual cells, which are genetically identical, none-the-less can have substantially different responses to outside stimuli, and markedly different lifespans, indicating the epigenetic factors play an important role in gene expression and aging as well as genetic factors.

According to the GenAge database of aging-related genes there are over 700 genes associated with aging in model organisms: 555 in the soil roundworm (Caenorhabditis elegans), 87 in the bakers' yeast (Saccharomyces cerevisiae), 75 in the fruit fly (Drosophila melanogaster) and 68 in the mouse (Mus musculus).^[40] The following is a list of genes connected to longevity through research ^[40] on model organisms:

Podospora	Saccharomyces	Caenorhabditis	Drosophila	Mus
grisea	LAG1	daf-2	sod1	Prop-1
	LAC1	age-1/daf-23	cat1	p66shc (Not independently verified)
	pit-1	Ghr
	RAS1	daf-18	mth	mclk1
	RAS2	akt-1/akt-2
	PHB1	daf-16
	PHB2	daf-12
	CDC7	ctl-1
	BUD1	old-1
	RTG2	spe-26
	RPD3	clk-1
	HDA1	mev-1
	SIR2
		aak-2
	SIR4-42
	UTH4
	YGL023
	SGS1
	RAD52
	FOB1

Cellular senescence

As noted above, senescence is not universal. It was once thought that senescence did not occur in single-celled organisms that reproduce through the process of cellular mitosis.^[41] Recent investigation has unveiled a more complex picture. Single cells do accumulate age-related damage. On mitosis the debris is not evenly divided between the new cells. Instead it passes to one of the cells leaving the other cell pristine. With successive generations the cell population becomes a mosaic of cells with half ageless and the rest with varying degrees of senescence.^[42]

Moreover, cellular senescence is not observed in several organisms, including perennial plants, sponges, corals, and lobsters. In those species where cellular senescence is observed, cells eventually become post-mitotic when they can no longer replicate themselves through the process of cellular mitosis; i.e., cells experience replicative senescence. How and why some cells become post-mitotic in some species has been the subject of much research and speculation, but (as noted above) it is sometimes suggested that cellular senescence evolved as a way to prevent the onset and spread of cancer. Somatic cells that have divided many times will have accumulated DNA mutations and would therefore be in danger of becoming cancerous if cell division continued. As such, it is becoming apparent that senescent cells undergo conversion to an immunogenic phenotype that enables them to be eliminated by the immune system.^[43]

Lately, the role of telomeres in cellular senescence has aroused general interest, especially with a view to the possible genetically adverse effects of cloning. The successive shortening of the chromosomal telomeres with each cell cycle is also believed to limit the number of divisions of the cell, thus contributing to aging. There have, on the other hand, also been reports that cloning could alter the shortening of telomeres. Some cells do not age and are, therefore, described as being "biologically immortal". It is theorized by some that when it is discovered exactly what allows these cells, whether it be the result of telomere lengthening or not, to divide without limit that it will be possible to genetically alter other cells to have the same capability. It is further theorized that it will eventually be possible to genetically engineer all cells in the human body to have this capability by employing gene therapy and, therefore, stop or reverse aging, effectively making the entire organism potentially immortal.

The length of the telomere strand has senescent effects; telomere shortening activates extensive alterations in alternative RNA splicing that produce senescent toxins such as progerin, which degrades the tissue and makes it more prone to failure.^[44]

Cancer cells are usually immortal. In about 85% of tumors, this evasion of cellular senescence is the result of up-activation of their telomerase genes.^[45] This simple observation suggests that reactivation of telomerase in healthy individuals could greatly increase their cancer risk.

Ned Sharpless and collaborators demonstrated the first in vivo link between p16-expression and lifespan.^[46] They found reduced p16 expression in some tissues of mice with mutations that extend lifespan, as well as in mice that had their lifespan extended by food restriction. Jan van Deursen and Darren Baker in collaboration with Andre Terzic at the Mayo Clinic in Rochester, Minn., provided the first in vivo evidence for a causal link between cellular senescence and aging by preventing the accumulation of senescent cells in BubR1 progeroid mice.^[47] In the absence of senescent cells, the mice’s tissues showed a major improvement in the usual burden of age-related disorders. They did not develop cataracts, avoided the usual wasting of muscle with age. They retained the fat layers in the skin that usually thin out with age and, in people, cause wrinkling. A second study led by Jan van Deursen in collaboration with a team of collaborators at the Mayo Clinic and Groningen University, provided the first direct in vivo evidence that cellular senescence causes signs of aging by eliminating senescent cells from progeroid mice by introducing a drug-inducible suicide gene and then treating the mice with the drug to kill senescent cells selectively, as opposed to decreasing whole body p16.^[10] Another Mayo study led by James Kirkland in collaboration with Scripps and other groups demonstrated that senolytics, drugs that target senescent cells, enhance cardiac function and improve vascular reactivity in old mice, alleviate gait disturbance caused by radiation in mice, and delay frailty, neurological dysfunction, and osteoporosis in progeroid mice. Discovery of senolytic drugs was based on a hypothesis-driven approach: the investigators leveraged the observation that senescent cells are resistant to apoptosis to discover that pro-survival pathways are up-regulated in these cells. They demonstrated that these survival pathways are the "Achilles heel" of senescent cells using RNA interference approaches, including Bcl-2-, AKT-, p21-, and tyrosine kinase-related pathways. They then used drugs known to target the identified pathways and showed these drugs kill senescent cells by apoptosis in culture and decrease senescent cell burden in multiple tissues in vivo. Importantly, these drugs had long term effects after a single dose, consistent with removal of senescent cells, rather than a temporary effect requiring continued presence of the drugs. This was the first study to show that clearing senescent cells enhances function in chronologically aged mice.^[48]

Chemical damage

Elderly Klamath woman photographed by Edward S. Curtis in 1924

One of the earliest aging theories was the Rate of Living Hypothesis described by Raymond Pearl in 1928^[49] (based on earlier work by Max Rubner), which states that fast basal metabolic rate corresponds to short maximum life span.

While there may be some validity to the idea that for various types of specific damage detailed below that are by-products of metabolism, all other things being equal, a fast metabolism may reduce lifespan, in general this theory does not adequately explain the differences in lifespan either within, or between, species. Calorically restricted animals process as much, or more, calories per gram of body mass, as their ad libitum fed counterparts, yet exhibit substantially longer lifespans.^{[citation needed]} Similarly, metabolic rate is a poor predictor of lifespan for birds, bats and other species that, it is presumed, have reduced mortality from predation, and therefore have evolved long lifespans even in the presence of very high metabolic rates.^[50] In a 2007 analysis it was shown that, when modern statistical methods for correcting for the effects of body size and phylogeny are employed, metabolic rate does not correlate with longevity in mammals or birds.^[51] (For a critique of the Rate of Living Hypothesis see Living fast, dying when?^[52])

With respect to specific types of chemical damage caused by metabolism, it is suggested that damage to long-lived biopolymers, such as structural proteins or DNA, caused by ubiquitous chemical agents in the body such as oxygen and sugars, are in part responsible for aging. The damage can include breakage of biopolymer chains, cross-linking of biopolymers, or chemical attachment of unnatural substituents (haptens) to biopolymers.

Under normal aerobic conditions, approximately 4% of the oxygen metabolized by mitochondria is converted to superoxide ion, which can subsequently be converted to hydrogen peroxide, hydroxyl radical and eventually other reactive species including other peroxides and singlet oxygen, which can, in turn, generate free radicals capable of damaging structural proteins and DNA. Certain metal ions found in the body, such as copper and iron, may participate in the process. (In Wilson's disease, a hereditary defect that causes the body to retain copper, some of the symptoms resemble accelerated senescence.) These processes termed oxidative stress are linked to the potential benefits of dietary polyphenol antioxidants, for example in coffee,^[53] red wine and tea.^[54]

Sugars such as glucose and fructose can react with certain amino acids such as lysine and arginine and certain DNA bases such as guanine to produce sugar adducts, in a process called glycation. These adducts can further rearrange to form reactive species, which can then cross-link the structural proteins or DNA to similar biopolymers or other biomolecules such as non-structural proteins. People with diabetes, who have elevated blood sugar, develop senescence-associated disorders much earlier than the general population, but can delay such disorders by rigorous control of their blood sugar levels. There is evidence that sugar damage is linked to oxidant damage in a process termed glycoxidation.

Free radicals can damage proteins, lipids or DNA. Glycation mainly damages proteins. Damaged proteins and lipids accumulate in lysosomes as lipofuscin. Chemical damage to structural proteins can lead to loss of function; for example, damage to collagen of blood vessel walls can lead to vessel-wall stiffness and, thus, hypertension, and vessel wall thickening and reactive tissue formation (atherosclerosis); similar processes in the kidney can lead to renal failure. Damage to enzymes reduces cellular functionality. Lipid peroxidation of the inner mitochondrial membrane reduces the electric potential and the ability to generate energy. It is probably no accident that nearly all of the so-called "accelerated aging diseases" are due to defective DNA repair enzymes.

It is believed that the impact of alcohol on aging can be partly explained by alcohol's activation of the HPA axis, which stimulates glucocorticoid secretion, long-term exposure to which produces symptoms of aging.^[55]

DNA damage theory

Alexander^[56] was the first to propose that DNA damage is the primary cause of aging. Early experimental evidence supporting this idea was reviewed by Gensler and Bernstein.^[57] By the early 1990s experimental support for this proposal was substantial, and further indicated that DNA damage due to reactive oxygen species was a major source of the DNA damages causing aging.^{[58][59][60][61][62]} The current state of evidence bearing on this theory is reviewed in DNA damage theory of aging and by Bernstein et al.^[63]

Reliability theory

Reliability theory suggests that biological systems start their adult life with a high load of initial damage. Reliability theory is a general theory about systems failure. It allows researchers to predict the age-related failure kinetics for a system of given architecture (reliability structure) and given reliability of its components. Reliability theory predicts that even those systems which are composed entirely of non-aging elements (with a constant failure rate) will nevertheless deteriorate (fail more often) with age, if these systems are redundant in irreplaceable elements. Aging, therefore, is a direct consequence of systems.
Reliability theory also predicts the late-life mortality deceleration with subsequent leveling-off, as well as the late-life mortality plateaus, as an inevitable consequence of redundancy exhaustion at extreme old ages. The theory explains why mortality rates increase exponentially with age (the Gompertz law) in many species, by taking into account the initial flaws (defects) in newly formed systems. It also explains why organisms "prefer" to die according to the Gompertz law, while technical devices usually fail according to the Weibull (power) law. Reliability theory allows to specify conditions when organisms die according to the Weibull distribution: Organisms should be relatively free of initial flaws and defects. The theory makes it possible to find a general failure law applicable to all adult and extreme old ages, where the Gompertz and the Weibull laws are just special cases of this more general failure law. The theory explains why relative differences in mortality rates of compared populations (within a given species) vanish with age (compensation law of mortality), and mortality convergence is observed due to the exhaustion of initial differences in redundancy levels.

Miscellanea

Biological clocks, which objectively measure the biological age of cells and tissues, may become useful for testing different biological aging theories.^[19]

A set of rare hereditary (genetic) disorders, each called progeria, has been known for some time. Sufferers exhibit symptoms resembling accelerated aging, including wrinkled skin. The cause of Hutchinson–Gilford progeria syndrome was reported in the journal Nature in May 2003.^[64] This report suggests that DNA damage, not oxidative stress, is the cause of this form of accelerated aging.

Recently, a kind of early senescence has been alleged to be a possible unintended outcome of early cloning experiments. The issue was raised in the case of Dolly the sheep, following her death from a contagious lung disease. The claim that Dolly's early death involved premature senescence has been vigorously contested,^[65] and Dolly's creator, Dr. Ian Wilmut has expressed the view that her illness and death were probably unrelated to the fact that she was a clone.