Growth hormone

From Wikipedia, the free encyclopedia

Growth hormone 1 (pituitary)
Growth hormone
Identifiers
Symbol	GH1
NCBI gene	2688
HGNC	4261
OMIM	139250
RefSeq	NM_022562
UniProt	P01241
Other data
Locus	Chr. 17 q22-q24

Growth hormone 2 (placental)
Identifiers
Symbol	GH2
NCBI gene	2689
HGNC	4262
OMIM	139240
RefSeq	NM_002059
UniProt	P01242
Other data
Locus	Chr. 17 q22-q24

Growth hormone (GH) or somatotropin, also known as human growth hormones (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also stimulates production of IGF-1 and increases the concentration of glucose and free fatty acids. It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

A recombinant form of hGH called somatreopleopin (INN) is used as a prescription drug to treat children's growth disorders and adult growth hormone deficiency. In the United States, it is only available legally from pharmacies by prescription from a licensed health care provider. In recent years in the United States, some health care providers are prescribing growth hormone in the elderly to increase vitality. While legal, the efficacy and safety of this use for HGH has not been tested in a clinical trial. Many of the functions of hGH remain unknown.

In its role as an anabolic agent, HGH has been used by competitors in sports since at least 1982, and has been banned by the IOC and NCAA. Traditional urine analysis does not detect doping with HGH, so the ban was not enforced until the early 2000s, when blood tests that could distinguish between natural and artificial HGH were starting to be developed. Blood tests conducted by WADA at the 2004 Olympic Games in Athens, Greece targeted primarily HGH. Use of the drug for performance enhancement is not currently approved by the FDA.

GH has been studied for use in raising livestock more efficiently in industrial agriculture and several efforts have been made to obtain governmental approval to use GH in livestock production. These uses have been controversial. In the United States, the only FDA-approved use of GH for livestock is the use of a cow-specific form of GH called bovine somatotropin for increasing milk production in dairy cows. Retailers are permitted to label containers of milk as produced with or without bovine somatotropin.

Nomenclature

The names somatotropin (STH) or somatotropic hormone refer to the growth hormone produced naturally in animals and extracted from carcasses. Hormone extracted from human cadavers is abbreviated hGH. The main growth hormone produced by recombinant DNA technology has the approved generic name (INN) somatropin and the brand name Humatrope, and is properly abbreviated rhGH in the scientific literature. Since its introduction in 1992 Humatrope has been a banned sports doping agent, and in this context is referred to as HGH.

Biology

Gene

Genes for human growth hormone, known as growth hormone 1 (somatotropin; pituitary growth hormone) and growth hormone 2 (placental growth hormone; growth hormone variant), are localized in the q22-24 region of chromosome 17 and are closely related to human chorionic somatomammotropin (also known as placental lactogen) genes. GH, human chorionic somatomammotropin, and prolactin belong to a group of homologous hormones with growth-promoting and lactogenic activity.

Structure

The major isoform of the human growth hormone is a protein of 191 amino acids and a molecular weight of 22,124 daltons. The structure includes four helices necessary for functional interaction with the GH receptor. It appears that, in structure, GH is evolutionarily homologous to prolactin and chorionic somatomammotropin. Despite marked structural similarities between growth hormone from different species, only human and Old World monkey growth hormones have significant effects on the human growth hormone receptor.

Several molecular isoforms of GH exist in the pituitary gland and are released to blood. In particular, a variant of approximately 20 kDa originated by an alternative splicing is present in a rather constant 1:9 ratio, while recently an additional variant of ~ 23-24 kDa has also been reported in post-exercise states at higher proportions. This variant has not been identified, but it has been suggested to coincide with a 22 kDa glycosylated variant of 23 kDa identified in the pituitary gland. Furthermore, these variants circulate partially bound to a protein (growth hormone-binding protein, GHBP), which is the truncated part of the growth hormone receptor, and an acid-labile subunit (ALS).

Regulation

Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus. These cells release the peptides growth hormone-releasing hormone (GHRH or somatocrinin) and growth hormone-inhibiting hormone (GHIH or somatostatin) into the hypophyseal portal venous blood surrounding the pituitary. GH release in the pituitary is primarily determined by the balance of these two peptides, which in turn is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion.

Somatotropic cells in the anterior pituitary gland then synthesize and secrete GH in a pulsatile manner, in response to these stimuli by the hypothalamus. The largest and most predictable of these GH peaks occurs about an hour after onset of sleep with plasma levels of 13 to 72 ng/mL. Otherwise there is wide variation between days and individuals. Nearly fifty percent of GH secretion occurs during the third and fourth NREM sleep stages. Surges of secretion during the day occur at 3- to 5-hour intervals. The plasma concentration of GH during these peaks may range from 5 to even 45 ng/mL. Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night. Additional analysis of the pulsatile profile of GH described in all cases less than 1 ng/ml for basal levels while maximum peaks were situated around 10-20 ng/mL.

A number of factors are known to affect GH secretion, such as age, sex, diet, exercise, stress, and other hormones. Young adolescents secrete GH at the rate of about 700 μg/day, while healthy adults secrete GH at the rate of about 400 μg/day. Sleep deprivation generally suppresses GH release, particularly after early adulthood.

Stimulators of growth hormone (GH) secretion include:

• Peptide hormones
  • GHRH (somatocrinin) through binding to the growth hormone-releasing hormone receptor (GHRHR)
  • Ghrelin through binding to growth hormone secretagogue receptors (GHSR)
• Sex hormones
  • Increased androgen secretion during puberty (in males from testes and in females from adrenal cortex)
  • Testosterone and DHEA
  • Estrogen
• Clonidine and L-DOPA by stimulating GHRH release
• α4β2 nicotinic agonists, including nicotine, which also act synergistically with clonidine.
• Hypoglycemia, arginine and propranolol by inhibiting somatostatin release.
• Deep sleep
• Insulin
• Glucagon
• Niacin as nicotinic acid (vitamin B₃)
• Fasting
• Vigorous exercise 

Inhibitors of GH secretion include:

• GHIH (somatostatin) from the periventricular nucleus 
• circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus)
• Hyperglycemia
• Glucocorticoids
• Dihydrotestosterone
• Phenothiazines

In addition to control by endogenous and stimulus processes, a number of foreign compounds (xenobiotics such as drugs and endocrine disruptors) are known to influence GH secretion and function.

Function

Main pathways in endocrine regulation of growth

Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up). Like most other protein hormones, GH acts by interacting with a specific receptor on the surface of cells. 

Increased height during childhood is the most widely known effect of GH. Height appears to be stimulated by at least two mechanisms:

1. Because polypeptide hormones are not fat-soluble, they cannot penetrate cell membranes. Thus, GH exerts some of its effects by binding to receptors on target cells, where it activates the MAPK/ERK pathway. Through this mechanism GH directly stimulates division and multiplication of chondrocytes of cartilage.
2. GH also stimulates, through the JAK-STAT signaling pathway, the production of insulin-like growth factor 1 (IGF-1, formerly known as somatomedin C), a hormone homologous to proinsulin. The liver is a major target organ of GH for this process and is the principal site of IGF-1 production. IGF-1 has growth-stimulating effects on a wide variety of tissues. Additional IGF-1 is generated within target tissues, making it what appears to be both an endocrine and an autocrine/paracrine hormone. IGF-1 also has stimulatory effects on osteoblast and chondrocyte activity to promote bone growth.

In addition to increasing height in children and adolescents, growth hormone has many other effects on the body:

• Increases calcium retention, and strengthens and increases the mineralization of bone
• Increases muscle mass through sarcomere hypertrophy
• Promotes lipolysis
• Increases protein synthesis
• Stimulates the growth of all internal organs excluding the brain
• Plays a role in homeostasis
• Reduces liver uptake of glucose
• Promotes gluconeogenesis in the liver
• Contributes to the maintenance and function of pancreatic islets
• Stimulates the immune system
• Increases deiodination of T4 to T3

Biochemistry

GH has a short biological half-life of about 10 to 20 minutes.

Clinical significance

Excess

The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH. For years, the principal clinical problems are those of GH excess. Eventually, the adenoma may become large enough to cause headaches, impair vision by pressure on the optic nerves, or cause deficiency of other pituitary hormones by displacement.

Prolonged GH excess thickens the bones of the jaw, fingers and toes, resulting heaviness of the jaw and increased size of digits, referred to as acromegaly. Accompanying problems can include sweating, pressure on nerves (e.g. carpal tunnel syndrome), muscle weakness, excess sex hormone-binding globulin (SHBG), insulin resistance or even a rare form of type 2 diabetes, and reduced sexual function.

GH-secreting tumors are typically recognized in the fifth decade of life. It is extremely rare for such a tumor to occur in childhood, but, when it does, the excessive GH can cause excessive growth, traditionally referred to as pituitary gigantism.

Surgical removal is the usual treatment for GH-producing tumors. In some circumstances, focused radiation or a GH antagonist such as pegvisomant may be employed to shrink the tumor or block function. Other drugs like octreotide (somatostatin agonist) and bromocriptine (dopamine agonist) can be used to block GH secretion because both somatostatin and dopamine negatively inhibit GHRH-mediated GH release from the anterior pituitary.

Deficiency

The effects of growth hormone (GH) deficiency vary depending on the age at which they occur. Alterations in somatomedin can result in growth hormone deficiency with two known mechanisms; failure of tissues to respond to somatomedin, or failure of the liver to produce somatomedin. Major manifestations of GH deficiency in children are growth failure, the development of a short stature, and delayed sexual maturity. In adults, somatomedin alteration contributes to increased osteoclast activity, resulting in weaker bones that are more prone to pathologic fracture and osteoporosis. However, deficiency is rare in adults, with the most common cause being a pituitary adenoma. Other adult causes include a continuation of a childhood problem, other structural lesions or trauma, and very rarely idiopathic GHD.

Adults with GHD "tend to have a relative increase in fat mass and a relative decrease in muscle mass and, in many instances, decreased energy and quality of life".

Diagnosis of GH deficiency involves a multiple-step diagnostic process, usually culminating in GH stimulation tests to see if the patient's pituitary gland will release a pulse of GH when provoked by various stimuli.

Psychological effects

Quality of life

Several studies, primarily involving patients with GH deficiency, have suggested a crucial role of GH in both mental and emotional well-being and maintaining a high energy level. Adults with GH deficiency often have higher rates of depression than those without. While GH replacement therapy has been proposed to treat depression as a result of GH deficiency, the long-term effects of such therapy are unknown.

Cognitive function

GH has also been studied in the context of cognitive function, including learning and memory. GH in humans appears to improve cognitive function and may be useful in the treatment of patients with cognitive impairment that is a result of GH deficiency.

Medical uses

Replacement therapy

Treatment with exogenous GH is indicated only in limited circumstances, and needs regular monitoring due to the frequency and severity of side-effects. GH is used as replacement therapy in adults with GH deficiency of either childhood-onset or adult-onset (usually as a result of an acquired pituitary tumor). In these patients, benefits have variably included reduced fat mass, increased lean mass, increased bone density, improved lipid profile, reduced cardiovascular risk factors, and improved psychosocial well-being.

Other approved uses

GH can be used to treat conditions that produce short stature but are not related to deficiencies in GH. However, results are not as dramatic when compared to short stature that is solely attributable to deficiency of GH. Examples of other causes of shortness often treated with GH are Turner syndrome, chronic kidney failure, Prader–Willi syndrome, intrauterine growth restriction, and severe idiopathic short stature. Higher ("pharmacologic") doses are required to produce significant acceleration of growth in these conditions, producing blood levels well above normal ("physiologic"). Despite the higher doses, side-effects during treatment are rare, and vary little according to the condition being treated. 

 

One version of rHGH has also been FDA approved for maintaining muscle mass in wasting due to AIDS.

Off-label use

Off-label prescription of HGH is controversial and may be illegal.

Claims for GH as an anti-aging treatment date back to 1990 when the New England Journal of Medicine published a study wherein GH was used to treat 12 men over 60. At the conclusion of the study, all the men showed statistically significant increases in lean body mass and bone mineral density, while the control group did not. The authors of the study noted that these improvements were the opposite of the changes that would normally occur over a 10- to 20-year aging period. Despite the fact the authors at no time claimed that GH had reversed the aging process itself, their results were misinterpreted as indicating that GH is an effective anti-aging agent. This has led to organizations such as the controversial American Academy of Anti-Aging Medicine promoting the use of this hormone as an "anti-aging agent".

A Stanford University School of Medicine meta-analysis of clinical studies on the subject published in early 2007 showed that the application of GH on healthy elderly patients increased muscle by about 2 kg and decreased body fat by the same amount. However, these were the only positive effects from taking GH. No other critical factors were affected, such as bone density, cholesterol levels, lipid measurements, maximal oxygen consumption, or any other factor that would indicate increased fitness. Researchers also did not discover any gain in muscle strength, which led them to believe that GH merely let the body store more water in the muscles rather than increase muscle growth. This would explain the increase in lean body mass.

GH has also been used experimentally to treat multiple sclerosis, to enhance weight loss in obesity, as well as in fibromyalgia, heart failure, Crohn's disease and ulcerative colitis, and burns. GH has also been used experimentally in patients with short bowel syndrome to lessen the requirement for intravenous total parenteral nutrition.

In 1990, the US Congress passed an omnibus crime bill, the Crime Control Act of 1990, that amended the Federal Food, Drug, and Cosmetic Act, that classified anabolic steroids as controlled substances and added a new section that stated that a person who "knowingly distributes, or possesses with intent to distribute, human growth hormone for any use in humans other than the treatment of a disease or other recognized medical condition, where such use has been authorized by the Secretary of Health and Human Services" has committed a felony.

The Drug Enforcement Administration of the US Department of Justice considers off-label prescribing of HGH to be illegal, and to be a key path for illicit distribution of HGH. This section has also been interpreted by some doctors, most notably the authors of a commentary article published in the Journal of the American Medical Association in 2005, as meaning that prescribing HGH off-label may be considered illegal. And some articles in the popular press, such as those criticizing the pharmaceutical industry for marketing drugs for off-label use (which is clearly illegal) have made strong statements about whether doctors can prescribe HGH off-label: "Unlike other prescription drugs, HGH may be prescribed only for specific uses. U.S. sales are limited by law to treat a rare growth defect in children and a handful of uncommon conditions like short bowel syndrome or Prader-Willi syndrome, a congenital disease that causes reduced muscle tone and a lack of hormones in sex glands." At the same time, anti-aging clinics where doctors prescribe, administer, and sell HGH to people are big business. In a 2012 article in Vanity Fair, when asked how HGH prescriptions far exceed the number of adult patients estimated to have HGH-deficiency, Dragos Roman, who leads a team at the FDA that reviews drugs in endocrinology, said "The F.D.A. doesn't regulate off-label uses of H.G.H. Sometimes it's used appropriately. Sometimes it's not."

Side effects

Injection-site reaction is common. More rarely, patients can experience joint swelling, joint pain, carpal tunnel syndrome, and an increased risk of diabetes. In some cases, the patient can produce an immune response against GH. GH may also be a risk factor for Hodgkin's lymphoma.

One survey of adults that had been treated with replacement cadaver GH (which has not been used anywhere in the world since 1985) during childhood showed a mildly increased incidence of colon cancer and prostate cancer, but linkage with the GH treatment was not established.

Performance enhancement

The first description of the use of GH as a doping agent was Dan Duchaine's "Underground Steroid handbook" which emerged from California in 1982; it is not known where and when GH was first used this way.

Athletes in many sports have used human growth hormone in order to attempt to enhance their athletic performance. Some recent studies have not been able to support claims that human growth hormone can improve the athletic performance of professional male athletes. Many athletic societies ban the use of GH and will issue sanctions against athletes who are caught using it. However, because GH is a potent endogenous protein, it is very difficult to detect GH doping. In the United States, GH is legally available only by prescription from a medical doctor.

Dietary supplements

To capitalize on the idea that GH might be useful to combat aging, companies selling dietary supplements have websites selling products linked to GH in the advertising text, with medical-sounding names described as "HGH Releasers". Typical ingredients include amino acids, minerals, vitamins, and/or herbal extracts, the combination of which are described as causing the body to make more GH with corresponding beneficial effects. In the United States, because these products are marketed as dietary supplements, it is illegal for them to contain GH, which is a drug. Also, under United States law, products sold as dietary supplements cannot have claims that the supplement treats or prevents any disease or condition, and the advertising material must contain a statement that the health claims are not approved by the FDA. The FTC and the FDA do enforce the law when they become aware of violations.

Agricultural use

In the United States, it is legal to give a bovine GH to dairy cows to increase milk production, and is legal to use GH in raising cows for beef; see article on Bovine somatotropin, cattle feeding, dairy farming and the beef hormone controversy.

The use of GH in poultry farming is illegal in the United States. Similarly, no chicken meat for sale in Australia is administered hormones.

Several companies have attempted to have a version of GH for use in pigs (porcine somatotropin) approved by the FDA but all applications have been withdrawn.

Drug development history

The identification, purification and later synthesis of growth hormone is associated with Choh Hao Li. Genentech pioneered the first use of recombinant human growth hormone for human therapy in 1981. 

Prior to its production by recombinant DNA technology, growth hormone used to treat deficiencies was extracted from the pituitary glands of cadavers. Attempts to create a wholly synthetic HGH failed. Limited supplies of HGH resulted in the restriction of HGH therapy to the treatment of idiopathic short stature. Very limited clinical studies of growth hormone derived from an Old World monkey, the rhesus macaque, were conducted by John C. Beck and colleagues in Montreal, in the late 1950s. The study published in 1957, which was conducted on "a 13-year-old male with well-documented hypopituitarism secondary to a crainiophyaryngioma," found that: "Human and monkey growth hormone resulted in a significant enhancement of nitrogen storage ... (and) there was a retention of potassium, phosphorus, calcium, and sodium. ... There was a gain in body weight during both periods. ... There was a significant increase in urinary excretion of aldosterone during both periods of administration of growth hormone. This was most marked with the human growth hormone. ... Impairment of the glucose tolerance curve was evident after 10 days of administration of the human growth hormone. No change in glucose tolerance was demonstrable on the fifth day of administration of monkey growth hormone." The other study, published in 1958, was conducted on six people: the same subject as the Science paper; an 18-year-old male with statural and sexual retardation and a skeletal age of between 13 and 14 years; a 15-year-old female with well-documented hypopituitarism secondary to a craniopharyngioma; a 53-year-old female with carcinoma of the breast and widespread skeletal metastases; a 68-year-old female with advanced postmenopausal osteoporosis; and a healthy 24-year-old medical student without any clinical or laboratory evidence of systemic disease.

In 1985, unusual cases of Creutzfeldt–Jakob disease were found in individuals that had received cadaver-derived HGH ten to fifteen years previously. Based on the assumption that infectious prions causing the disease were transferred along with the cadaver-derived HGH, cadaver-derived HGH was removed from the market.

In 1985, biosynthetic human growth hormone replaced pituitary-derived human growth hormone for therapeutic use in the U.S. and elsewhere.

As of 2005, recombinant growth hormones available in the United States (and their manufacturers) included Nutropin (Genentech), Humatrope (Lilly), Genotropin (Pfizer), Norditropin (Novo), and Saizen (Merck Serono). In 2006, the U.S. Food and Drug Administration (FDA) approved a version of rHGH called Omnitrope (Sandoz). A sustained-release form of growth hormone, Nutropin Depot (Genentech and Alkermes) was approved by the FDA in 1999, allowing for fewer injections (every 2 or 4 weeks instead of daily); however, the product was discontinued by Genentech/Alkermes in 2004 for financial reasons (Nutropin Depot required significantly more resources to produce than the rest of the Nutropin line).

Anti-aging movement

From Wikipedia, the free encyclopedia

 

 

The anti-aging movement is a social movement devoted to eliminating or reversing aging, or reducing the effects of it. A substantial portion of the attention of the movement is on the possibilities for life extension, but there is also interest in techniques such as cosmetic surgery which ameliorate the effects of aging rather than delay or defeat it.

Two popular proponents of the anti-aging movement include Ray Kurzweil, who says humanity can defeat aging through the advance of technology, and Aubrey De Grey, who says that the human body is a very complicated machine and, thus, can be repaired indefinitely. Other scientists and significant contributors to the movement include molecular biologists, geneticists, and biomedical gerontologists such as Gary Ruvkun, Cynthia Kenyon, and Arthur D. Levinson. However, figures in the gerontology community in 2003 tried to distance their research from the perceived pseudoscience of the movement.

Anti-aging medicine

Anti-aging medicine has become a budding and rapidly growing medical specialty as physicians who initially sought treatment for themselves have received training and certification in its practice by organizations such as the American Academy of Anti-Aging Medicine (A4M) co-founded by Dr Robert M. Goldman and Ronald Klatz.

Human growth hormone

Central to anti-aging medicine is administration of human growth hormone. Clinical studies have shown that low-dose growth hormone (GH) treatment for adults with GH deficiency changes the body composition by increasing muscle mass, decreasing fat mass, and increasing bone density and muscle strength. It also improves cardiovascular parameters (i.e. decrease of LDL cholesterol) and affects the quality of life without significant side effects. However, it is also said to have potentially dangerous side-effects when used in injectable form, if proper protocols are not followed. It is not approved for use in healthy aging patients, though many have been using it for this reason for decades now. That restriction is sidestepped by means of a diagnosis of some injury, organic condition, or adult growth hormone deficiency which supposedly has resulted in reduced secretion of the hormone.

Menopausal hormone drugs

Administration of estrogen and other hormones such as progestin were popularized by the 1966 book Feminine Forever by Robert A. Wilson. However, the increase of the use of estrogen was shown to be associated with an increased risk of cancer. Later, in 2002, research into the long-term effects of estrogen on post-menopausal women, the Women's Health Initiative, produced evidence that there were serious side effects. Physicians who prescribe the hormones now prescribe low doses of the drugs. Research into the long-term effects of hormone replacement therapy is continuing, with a 2017 Cochrane systematic review concluding that long-term use may decrease the risk of bone fractures or postmenopausal osteoporosis, but increase the risk of stroke, heart attacks, endometrial cancer, and breast cancer. Hormone therapy is generally only recommended for postmenopausal women who are at a high risk of osteoporosis when non-hormonal treatments are not suitable. Hormone therapy is not suitable or advised for treating cardiovascular disease, dementia, or for preventing cognitive decline in postmenopausal women. The risks of long-term hormonal therapy for women under 50 years of age have not been determined.

Scientific approaches

Biogerontology is a scientific discipline which has the same area of interest but, as a branch of gerontology, takes a more conservative approach. Caloric Restriction is a phenomenon introduced in anti-aging techniques which focuses on depletion of calories and taking the right amount of nutrients necessary for growth.

Calorie Restriction

Calorie Restriction (CR) refers to a dietary restriction that focuses on less calorie intake to increase longevity and reduce the age-related diseases in humans. Calorie restriction maintains a low-calorie intake that helps to regulate the rate of aging and increases the youthfulness of an individual or animal. Low-Calorie intake has directly been correlated to negative energy balance which promotes low Body Mass Index (BMI) and comparatively high plasma dehydroepiandrosterone (DHEA) for improved life expectancy. Calorie Restriction has widely been practiced by pregnant women and people with pre-existing medical conditions such as diabetes. The right amount of calorie restriction help pregnant women to achieve positive weight gain whereas a significant drop in calorie intake can lead to hypothalamic alterations leading to long-term effects in the offspring. Moderate CR in diabetic patients increases insulin sensitivity and reduces the amount of hepatic fat in obese individual and type-2 diabetes. Long term CR in older animals results in stem cell function similar to that of the younger groups. The active stem cell function helps in enhanced recovery of the damaged skeletal muscle tissue, which is comparatively slow in older individuals than in younger individuals. CR in the United States has shown a prolonged life span in women than a man as women tend to consume 25% fewer calories than a man in their lifetime. The statistical analysis of CR, available for anti-aging movement in humans is not sufficient enough to prove the prolonged lifespan associated with CR.

Mass movement

A substantial fraction of older people, taking their cue from alternative medicine, purchase and use herbal supplements and other products which promise relief from the incidents and dangers of aging. Some products are not effective while others hold promise.

Reception

There are at least two opposite views on the prospects of anti-aging research and development. One group states that there is a great deal of over-heated rhetoric in use with respect to life extension with over-optimistic projections on the part of its advocates. They also claim that there is little evidence that any significant breakthrough has been made, or is on the horizon. Some state that this is largely due to a current lack of funding or interest in the issue. A study of the common supplements and hormone treatments used published in 2006 in the Cleveland Clinic Journal of Medicine showed that none of them are effective with respect to extending life. Another group notices that recent scientific successes in rejuvenation and extending the lifespan of model animals (mice 2.5 times, yeast and nematodes 10 times) and discovery of variety of species (including humans of advanced ages) having negligible senescence give hope to achieve negligible senescence (cancel ageing) for younger humans, reverse ageing, or at least significantly delay it. Moreover, stopping or delaying aging should be a focus of the modern science and medicine since ageing is the major cause of mortality in the world.

Though some scientists think curing aging is impossible, there are some criticisms of both the time frame life extensionists envision (the first, perhaps somewhat crude, treatments within the next several decades, or at least before the beginning of the 22nd century) and of whether curing aging is even desirable. Common criticisms of the idea of life extension are fears it will cause the world to be more overpopulated; however, De Grey counters that by saying that since menopause would also be delayed, women could wait longer to have children and, thus, the rate of growth would actually decline as a result. Also, the slowly growing population would buy centuries of time to figure out new places to live, such as space colonies.

From Wikipedia, the free encyclopedia

History

Aesthetics of nature developed as a sub-field of philosopy

Aesthetics of nature

ethical ethics. In the 18th and 19th century, the aesthetics of nature advanced the concepts of disinterestedness, the pictures, and the introduction of the idea of positive aesthetics. The first major developments of nature occurred in the 18th century. The concept of disinterestedness had been explained by many thinkers. Anthony Ashley-Cooper introduced the concept as a way of characterizing the notion of the aesthetic, later magnified by Francis Hutcheson, who expanded it to exclude personal and utilitarianism interests and associations of a more general nature from aesthetic experience. This concept was further developed by Archibald Alison who referred it to a particular state of mind.

Theories

The theory of disinterestedness opened doors for a better understanding of the aesthetics dimensions of nature in terms of three conceptualizations:

1. The idea of beautiful: this applied to tamed and cultivated European gardens and landscapes
2. The idea of the sublime: this explained the threatening and terrifying side of nature such as mountains and wilderness; however, when it is viewed through the disinterestedness perspective, it can be aesthetically appreciated rather than feared or neglected
3. The notion of the picturesque: the term "picturesque" means "picture-like", where the natural world is experienced as if it is divided into art-like scenes

Objects experienced as beautiful tend to be small, smooth, and fair in color. In contrast, objects viewed as sublime tend to be powerful, intense and terrifying. Picturesque items are a mixture of both, which can be seen as varied and irregular, rich and forceful, and even vibrant.

21st century developments

Cognitive and non-cognitive approaches of nature have directed their focus from natural environments to the consideration of human and human-influenced environments and developed aesthetic investigations of everyday life. (Carlson and Lintott, 2007; Parsons 2008a; Carlson 2010)

Human Perspectives and Relationship with Nature

People may be mistaken by the art object analogy. For instance, a sandhill crane is not an art object; an art object is not a sandhill crane. In fact, an art object should be called an artifact. The crane is wildlife on its own and is not an art object. This can be related to Satio's definition of the cognitive view. In elaboration, the crane lives through various ecosystems such as Yellowstone. Nature is a living system which includes animals, plants, and Eco-systems. In contrast, an art object has no regeneration, evolutionary history, or metabolism. An individual may be in the forest and perceive it as beautiful because of the plethora of colors such as red, green, and yellow. This is a result of the chemicals interacting with chlorophyll. An individual's aesthetic experience may increase; however, none of the things mentioned have anything to do with what is really going on in the forest. The chlorophyll is capturing solar energy and the residual chemicals protect the trees from insect grazing.

Any color perceived by human visitors for a few hours is entirely different from what is really happening. According to Leopold, the three features of ecosystems that generate land ethic are integrity, stability and beauty. None of the mentioned features are real in nature. Ecosystems are not stable: they are dramatically changing and they have little integration; ergo, beauty is in the eye of the beholder.

Objectives

In a Post-Modern approach, when an individual engages in aesthetically appreciating a natural thing, we give meaning to the thing we appreciate and in that meaning, we express and develop our own attitudes, values and beliefs. Our interest in natural things are not only a passive reflection of our inclinations, as Croce describes as the appreciation of nature as looking in a mirror, or what we might call our inward life; but may instead be the things we come across in nature that engage and stimulate our imagination. As a result, we are challenged to think differently and apply thoughts and associations to in new situations and ways.

As a characterization of the appreciation of art, nature aestheticists argue that post modernism is a mistaken view because we do not have a case of anything goes. The aesthetics appreciation of art is governed by some normative standards. In the world of art, criticism may take place when people come together and discuss books and films or critics write appraisals for publications. On the contrary, there are not obvious instances of debate and appraisals where different judgments about the aesthetics of character of nature are evaluated.

 

Biological immortality

From Wikipedia, the free encyclopedia

 

Biological immortality (sometimes referred to as bio-indefinite mortality) is a state in which the rate of mortality from senescence is stable or decreasing, thus decoupling it from chronological age. Various unicellular and multicellular species, including some vertebrates, achieve this state either throughout their existence or after living long enough. A biologically immortal living being can still die from means other than senescence, such as through injury, disease, or lack of available resources.

This definition of immortality has been challenged in the Handbook of the Biology of Aging, because the increase in rate of mortality as a function of chronological age may be negligible at extremely old ages, an idea referred to as the late-life mortality plateau. The rate of mortality may cease to increase in old age, but in most cases that rate is typically very high.

The term is also used by biologists to describe cells that are not subject to the Hayflick limit on how many times they can divide.

Cell lines

Biologists chose the word "immortal" to designate cells that are not subject to the Hayflick limit, the point at which cells can no longer divide due to DNA damage or shortened telomeres. Prior to Leonard Hayflick's theory, Alexis Carrel hypothesized that all normal somatic cells were immortal.

The term "immortalization" was first applied to cancer cells that expressed the telomere-lengthening enzyme telomerase, and thereby avoided apoptosis—i.e. cell death caused by intracellular mechanisms. Among the most commonly used cell lines are HeLa and Jurkat, both of which are immortalized cancer cell lines. HeLa cells originated from a sample of cervical cancer taken from Henrietta Lacks in 1951. These cells have been and still are widely used in biological research such as creation of the polio vaccine, sex hormone steroid research, and cell metabolism. Normal stem cells and germ cells can also be said to be immortal (when humans refer to the cell line).

Immortal cell lines of cancer cells can be created by induction of oncogenes or loss of tumor suppressor genes. One way to induce immortality is through viral-mediated induction of the large T‑antigen, commonly introduced through simian virus 40 (SV-40).

Organisms

According to the Animal Aging and Longevity Database, the list of organisms with negligible aging (along with estimated longevity in the wild) includes:

• Blanding's turtle (Emydoidea blandingii) – 77 years
• Olm (Proteus anguinus) – 102 years
• Eastern box turtle (Terrapene carolina) – 138 years
• Red sea urchin (Strongylocentrotus franciscanus) – 200 years
• Rougheye rockfish (Sebastes aleutianus) – 205 years
• Ocean quahog clam (Arctica islandica) – 507 years

In 2018, scientists working for Calico, a company owned by Alphabet, published a paper in the journal eLife which presents possible evidence that Heterocephalus glaber (Naked mole rat) do not face increased mortality risk due to aging.

Bacteria and some yeast

Many unicellular organisms age: as time passes, they divide more slowly and ultimately die. Asymmetrically dividing bacteria and yeast also age. However, symmetrically dividing bacteria and yeast can be biologically immortal under ideal growing conditions. In these conditions, when a cell splits symmetrically to produce two daughter cells, the process of cell division can restore the cell to a youthful state. However, if the parent asymmetrically buds off a daughter only the daughter is reset to the youthful state—the parent isn't restored and will go on to age and die. In a similar manner stem cells and gametes can be regarded as "immortal".

Hydra

Hydra

Hydras are a genus of the Cnidaria phylum. All cnidarians can regenerate, allowing them to recover from injury and to reproduce asexually. Hydras are simple, freshwater animals possessing radial symmetry and no post-mitotic cells. All hydra cells continually divide.  It has been suggested that hydras do not undergo senescence, and, as such, are biologically immortal. In a four-year study, 3 cohorts of hydra did not show an increase in mortality with age. It is possible that these animals live much longer, considering that they reach maturity in 5 to 10 days. However, this does not explain how hydras are consequently able to maintain telomere lengths.

Jellyfish

Turritopsis dohrnii, or Turritopsis nutricula, is a small (5 millimeters (0.20 in)) species of jellyfish that uses transdifferentiation to replenish cells after sexual reproduction. This cycle can repeat indefinitely, potentially rendering it biologically immortal. This organism originated in the Caribbean sea, but has now spread around the world.

  Similar cases include hydrozoan Laodicea undulata and scyphozoan Aurelia sp.1.

Lobsters

Research suggests that lobsters may not slow down, weaken, or lose fertility with age, and that older lobsters may be more fertile than younger lobsters. This does not however make them immortal in the traditional sense, as they are significantly more likely to die at a shell moult the older they get (as detailed below).

Their longevity may be due to telomerase, an enzyme that repairs long repetitive sections of DNA sequences at the ends of chromosomes, referred to as telomeres. Telomerase is expressed by most vertebrates during embryonic stages but is generally absent from adult stages of life. However, unlike vertebrates, lobsters express telomerase as adults through most tissue, which has been suggested to be related to their longevity. Contrary to popular belief, lobsters are not immortal. Lobsters grow by moulting which requires a lot of energy, and the larger the shell the more energy is required. Eventually, the lobster will die from exhaustion during a moult. Older lobsters are also known to stop moulting, which means that the shell will eventually become damaged, infected, or fall apart and they die. The European lobster has an average life span of 31 years for males and 54 years for females.

Planarian flatworms

Polycelis felina, a freshwater planarian

Planarian flatworms have both sexually and asexually reproducing types. Studies on genus Schmidtea mediterranea suggest these planarians appear to regenerate (i.e. heal) indefinitely, and asexual individuals have an "apparently limitless [telomere] regenerative capacity fueled by a population of highly proliferative adult stem cells". "Both asexual and sexual animals display age-related decline in telomere length; however, asexual animals are able to maintain telomere lengths somatically (i.e. during reproduction by fission or when regeneration is induced by amputation), whereas sexual animals restore telomeres by extension during sexual reproduction or during embryogenesis like other sexual species. Homeostatic telomerase activity observed in both asexual and sexual animals is not sufficient to maintain telomere length, whereas the increased activity in regenerating asexuals is sufficient to renew telomere length... "

Lifespan: For sexually reproducing planaria: "the lifespan of individual planarian can be as long as 3 years, likely due to the ability of neoblasts to constantly replace aging cells". Whereas for asexually reproducing planaria: "individual animals in clonal lines of some planarian species replicating by fission have been maintained for over 15 years". They are "literally immortal."

Attempts to engineer biological immortality in humans

Although the premise that biological aging can be halted or reversed by foreseeable technology remains controversial, research into developing possible therapeutic interventions is underway. Among the principal drivers of international collaboration in such research is the SENS Research Foundation, a non-profit organization that advocates a number of what it claims are plausible research pathways that might lead to engineered negligible senescence in humans.

In 2015, Elizabeth Parrish, CEO of BioViva, treated herself using gene therapy with the goal of not just halting, but reversing aging.

For several decades, researchers have also pursued various forms of suspended animation as a means by which to indefinitely extend mammalian lifespan. Some scientists have voiced support for the feasibility of the cryopreservation of humans, known as cryonics. Cryonics is predicated on the concept that some people considered clinically dead by today's medicolegal standards are not actually dead according to information-theoretic death and can, in principle, be resuscitated given sufficient technological advances. The goal of current cryonics procedures is tissue vitrification, a technique first used to reversibly cryopreserve a viable whole organ in 2005.

Similar proposals involving suspended animation include chemical brain preservation. The non-profit Brain Preservation Foundation offers a cash prize valued at over $100,000 for demonstrations of techniques that would allow for high-fidelity, long-term storage of a mammalian brain.

In 2016, scientists at the Buck Institute for Research on Aging and the Mayo Clinic employed genetic and pharmacological approaches to ablate pro-aging senescent cells, extending healthy lifespan of mice by over 25%. The startup Unity Biotechnology is further developing this strategy in human clinical trials.

In early 2017, Harvard scientists headed by biologist David Sinclair announced they have tested a metabolic precursor that increases NAD+ levels in mice and have successfully reversed the cellular aging process and can protect the DNA from future damage. "The old mouse and young mouse cells are indistinguishable", David was quoted. Human trials were planned to begin shortly in what the team expect is 6 months at Brigham and Women's Hospital, in Boston.

In the September 2019 article, a group of scientists reported successfully reversing the epigenetic aging in humans.

Criticism

To achieve the more limited goal of halting the increase in mortality rate with age, a solution must be found to the fact that any intervention to remove senescent cells that creates competition among cells will increase age-related mortality from cancer.

Immortalism and immortality as a movement

In 2012 in Russia, and then in the United States, Israel, and the Netherlands, pro-immortality transhumanist political parties were launched. They aim to provide political support to anti-aging and radical life extension research and technologies and want to ensure the fastest possible—and at the same time, the least disruptive—societal transition to radical life extension, life without aging, and ultimately, immortality. They aim to make it possible to provide access to such technologies to the majority of people alive today.

Future medicine, life extension and "swallowing the doctor"

Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging. K. Eric Drexler, one of the founders of nanotechnology, postulated cell repair devices, including ones operating within cells and using as yet hypothetical molecular machines, in his 1986 book Engines of Creation. Raymond Kurzweil, a futurist and transhumanist, stated in his 2005 book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030. According to Richard Feynman, it was his former graduate student and collaborator Albert Hibbs who originally suggested to him in around 1959 the idea of a medical use for Feynman's theoretical micromachines. Hibbs suggested that certain repair machines might one day be reduced in size to the point that it would, in theory, be possible to (as Feynman put it) "swallow the doctor". The idea was incorporated into Feynman's 1959 essay There's Plenty of Room at the Bottom.