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137-499: Biomedical gerontology , also known as experimental gerontology and life extension, is a sub-discipline of biogerontology endeavoring to slow, prevent, and even reverse aging in both humans and animals. Biogerontologists vary in the degree to which they focus on the study of the aging process as a means of mitigating the diseases of aging , or as a method for extending lifespan. A relatively new interdisciplinary field called geroscience focuses on preventing diseases of aging and prolonging

274-596: A drug and are either expressed as proteins, interfere with the expression of proteins, or correct genetic mutations, has been proposed as a future strategy to prevent aging. CRISPR/Cas9 edits genes by precisely cutting DNA and then harnessing natural DNA repair processes to modify the gene in the desired manner. The system has two components: the Cas9 enzyme and a guide RNA. A large array of genetic modifications have been found to increase lifespan in model organisms such as yeast, nematode worms, fruit flies, and mice. As of 2013,

411-511: A futurist and transhumanist , stated in his 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 (circa 1959) the idea of a medical use for Feynman's theoretical nanomachines (see biological machine ). Hibbs suggested that certain repair machines might one day be reduced in size to

548-458: A spin trapping compound caused a decrease in the level of oxidized proteins in older gerbils but did not have an effect on younger gerbils. In addition, older gerbils performed cognitive tasks better during treatment but ceased functional capacity when treatment was discontinued, causing oxidized protein levels to increase. This led researchers to conclude that oxidation of cellular proteins is potentially important for brain function. According to

685-504: A better strategy for enhancing cancer cell cytotoxicity. James Watson and others have proposed that lack of intracellular ROS due to a lack of physical exercise may contribute to the malignant progression of cancer, because spikes of ROS are needed to correctly fold proteins in the endoplasmatic reticulum and low ROS levels may thus aspecifically hamper the formation of tumor suppressor proteins. Since physical exercise induces temporary spikes of ROS, this may explain why physical exercise

822-551: A biological context, ROS are byproducts of the normal metabolism of oxygen . ROS have roles in cell signaling and homeostasis . ROS are intrinsic to cellular functioning, and are present at low and stationary levels in normal cells. In plants, ROS are involved in metabolic processes related to photoprotection and tolerance to various types of stress. However, ROS can cause irreversible damage to DNA as they oxidize and modify some cellular components and prevent them from performing their original functions. This suggests that ROS has

959-454: A broad range of microbes including Salmonella enterica , Staphylococcus aureus , Serratia marcescens , and Aspergillus spp. Studies on the homeostasis of the Drosophila melanogaster ' s intestines have shown the production of ROS as a key component of the immune response in the gut of the fly. ROS acts both as a bactericide, damaging the bacterial DNA, RNA and proteins, as well as

1096-520: A collection of quite predictable diseases caused by the deterioration of the body." The two main arguments used are that aging is both inevitable and universal while diseases are not. However, not everyone agrees. Harry R. Moody, director of academic affairs for AARP , notes that what is normal and what is disease strongly depend on a historical context. David Gems , assistant director of the Institute of Healthy Ageing, argues that aging should be viewed as

1233-427: A combination of genetic engineering and caloric restriction . A 2009 review of longevity research noted: "Extrapolation from worms to mammals is risky at best, and it cannot be assumed that interventions will result in comparable life extension factors. Longevity gains from dietary restriction, or from mutations studied previously, yield smaller benefits to Drosophila than to nematodes, and smaller still to mammals. This

1370-866: A complex of cellular components such as fat, proteins, or from DNA; they are naturally generated in small amounts during the body's metabolic reactions. These conditions become more common as humans grow older and include diseases related to aging, such as dementia, cancer and heart disease. Amount of free radicals in the cell can be reduced with help of antioxidants . But there's a problem that some free radicals are used by organism as signal molecules, and too active general reduction of free radicals causes to organism more harm than good. Some time ago idea of slowing aging using antioxidants were very popular but now high doses of antioxidants are considered harmful. At present some scientists try to invent approaches of local suppression of free radicals only in certain places of cells. Efficiency of such approach remains to be unclear, research

1507-551: A contributing factor. The epigenetic clock , which relatively objectively measures the biological age of cells, are useful tool for testing different anti-aging approaches. The most famous epigenetic clock is Horvath's clock, but now already more accurate analogues have appeared. General imbalance theories of aging suggest that body systems, such as the endocrine , nervous , and immune systems , gradually decline and ultimately fail to function. The rate of failure varies system by system. The immunological theory of aging suggests that

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1644-423: A correlation seen between excessive amounts of ROS leading to apoptosis. The depolarization of the mitochondrial membrane is also characteristic of the initiation of autophagy. When mitochondria are damaged and begin to release ROS, autophagy is initiated to dispose of the damaging organelle. If a drug targets mitochondria and creates ROS, autophagy may dispose of so many mitochondria and other damaged organelles that

1781-679: A desire of humanity and a mainstay motif in the history of scientific pursuits and ideas throughout history, from the Sumerian Epic of Gilgamesh and the Egyptian Smith medical papyrus , all the way through the Taoists , Ayurveda practitioners, alchemists , hygienists such as Luigi Cornaro , Johann Cohausen and Christoph Wilhelm Hufeland , and philosophers such as Francis Bacon , René Descartes , Benjamin Franklin and Nicolas Condorcet . However,

1918-540: A disease. In response to the universality of aging, David Gems notes that it is as misleading as arguing that Basenji are not dogs because they do not bark. Because of the universality of aging he calls it a "special sort of disease". Robert M. Perlman, coined the terms "aging syndrome" and "disease complex" in 1954 to describe aging. The discussion whether aging should be viewed as a disease or not has important implications. One view is, this would stimulate pharmaceutical companies to develop life extension therapies and in

2055-720: A dual role; whether they will act as harmful, protective or signaling factors depends on the balance between ROS production and disposal at the right time and place. In other words, oxygen toxicity can arise both from uncontrolled production and from the inefficient elimination of ROS by the antioxidant system. ROS were also demonstrated to modify the visual appearance of fish . This potentially affects their behavior and ecology, such as their temperature control, their visual communication, their reproduction and survival. During times of environmental stress (e.g., UV or heat exposure), ROS levels can increase dramatically. This may result in significant damage to cell structures. Cumulatively, this

2192-693: A feared-self. Though many scientists state that life extension and radical life extension are possible, there are still no international or national programs focused on radical life extension. There are political forces working both for and against life extension. By 2012, in Russia, the United States, Israel, and the Netherlands, the Longevity political parties started. They aimed to provide political support to radical life extension research and technologies, and ensure

2329-494: A healthy youthful condition (agerasia ). The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists . The sale of purported anti-aging products such as supplements and hormone replacement is a lucrative global industry. For example, the industry that promotes the use of hormones as a treatment for consumers to slow or reverse the aging process in the US market generated about $ 50 billion of revenue

2466-459: A hoped-for self (e.g., keeping a youthful skin) or to avoid a feared-self (e.g., looking old). The research shows that when consumers pursue a hoped-for self, it is expectations of success that most strongly drive their motivation to use the product. The research also shows why doing badly when trying to avoid a feared self is more motivating than doing well. When product use is seen to fail it is more motivating than success when consumers seek to avoid

2603-408: A human corpse, with the hope that resuscitation may be possible in the future . It is regarded with skepticism within the mainstream scientific community and has been characterized as quackery . Another proposed life extension technology aims to combine existing and predicted future biochemical and genetic techniques. SENS proposes that rejuvenation may be obtained by removing aging damage via

2740-415: A longer period of decrepitude, and that the elderly in our current society are unhealthy. Religious people are no more likely to oppose life extension than the unaffiliated, though some variation exists between religious denominations. Most mainstream medical organizations and practitioners do not consider aging to be a disease. Biologist David Sinclair says: "I don't see aging as a disease, but as

2877-450: A low level, and regulatory standards are high. Aging is not recognized as a preventable condition by governments, indicating there is no clear pathway to approval of anti-aging medications. Further, anti-aging drug candidates are under constant review by regulatory authorities like the US Food and Drug Administration , which stated in 2023 that "no medication has been proven to slow or reverse

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3014-486: A methyl group can be added, by a DNA methyltransferase , to the 5th carbon of cytosine to form 5mC (see red methyl group added to form 5mC near the top of the first figure). The DNA methyltransferases most often form 5mC within the dinucleotide sequence "cytosine-phosphate-guanine" to form 5mCpG. This addition is a major type of epigenetic alteration and it can silence gene expression . Methylated cytosine can also be demethylated , an epigenetic alteration that can increase

3151-490: A novel aging route with substantially extended lifespan. In The Selfish Gene , Richard Dawkins describes an approach to life-extension that involves "fooling genes" into thinking the body is young. Dawkins attributes inspiration for this idea to Peter Medawar . The basic idea is that our bodies are composed of genes that activate throughout our lifetimes, some when we are young and others when we are older. Presumably, these genes are activated by environmental factors, and

3288-498: A population is lowered by infant and child mortality , which are frequently linked to infectious diseases or nutrition problems. Later in life, vulnerability to accidents and age-related chronic disease such as cancer or cardiovascular disease play an increasing role in mortality. Extension of life expectancy and lifespan can often be achieved by access to improved medical care, vaccinations , good diet , exercise , and avoidance of hazards such as smoking . Maximum lifespan

3425-526: A privileged few. In an extended metaphor entitled " The Fable of the Dragon-Tyrant ", Bostrom envisions death as a monstrous dragon who demands human sacrifices. In the fable, after a lengthy debate between those who believe the dragon is a fact of life and those who believe the dragon can and should be destroyed, the dragon is finally killed. Bostrom argues that political inaction allowed many preventable human deaths to occur. Controversy about life extension

3562-515: A problem that desperately needs to be solved; and recording artist Steve Aoki , who has been called "one of the most prolific campaigners for life extension". In 1991, the American Academy of Anti-Aging Medicine (A4M) was formed. The American Board of Medical Specialties recognizes neither anti-aging medicine nor the A4M's professional standing. In 2003, Aubrey de Grey and David Gobel formed

3699-484: A promising candidate for further research within the field. Their study suggests that high levels of iron in the blood likely reduce, and genes involved in metabolising iron likely increase healthy years of life in humans. The same month other scientists report that yeast cells of the same genetic material and within the same environment age in two distinct ways, describe a biomolecular mechanism that can determine which process dominates during aging and genetically engineer

3836-468: A rat model of premature aging found increased oxidative stress , reduced antioxidant enzyme activity and substantially greater DNA damage in the brain neocortex and hippocampus of the prematurely aged rats than in normally aging control rats. The DNA damage 8-OHdG is a product of ROS interaction with DNA. Numerous studies have shown that 8-OHdG increases with age (see DNA damage theory of aging ). ROS are constantly generated and eliminated in

3973-423: A result, production of NADPH is greatly enhanced, which functions as a cofactor to provide reducing power in many enzymatic reactions for macromolecular biosynthesis and at the same time rescuing the cells from excessive ROS produced during rapid proliferation. Cells counterbalance the detrimental effects of ROS by producing antioxidant molecules, such as reduced glutathione (GSH) and thioredoxin (TRX), which rely on

4110-552: A signalling molecule that induces repair mechanisms of the epithelium . The uracil released by microorganism triggers the production and activity of DUOX, the ROS-producing enzyme in the intestine. DUOX activity is induced according to the level of uracil in the gut; under basal conditions, it is down-regulated by the protein kinase MkP3 . The tight regulation of DUOX avoids excessive production of ROS and facilitates differentiation between benign and damage-inducing microorganisms in

4247-410: A significantly higher poly(ADP-ribosyl)ation capability than control cell lines from younger individuals. The cross-linking theory proposes that advanced glycation end-products (stable bonds formed by the binding of glucose to proteins) and other aberrant cross-links accumulating in aging tissues is the cause of aging. The crosslinking of proteins disables their biological functions. The hardening of

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4384-533: A single cell. 8-oxoguanine is the most abundant among various oxidized nitrogeneous bases observed. During DNA replication, DNA polymerase mispairs 8-oxoguanine with adenine, leading to a G→T transversion mutation. The resulting genomic instability directly contributes to carcinogenesis. Cellular transformation leads to cancer and interaction of atypical PKC-ζ isoform with p47phox controls ROS production and transformation from apoptotic cancer stem cells through blebbishield emergency program . Uncontrolled proliferation

4521-430: A variety of contexts. Use of stem cells taken from the umbilical cord or parts of the adult body may not provoke controversy. The controversies over cloning are similar, except general public opinion in most countries stands in opposition to reproductive cloning . Some proponents of therapeutic cloning predict the production of whole bodies, lacking consciousness, for eventual brain transplantation. Some critics dispute

4658-453: A variety of inflammatory responses including cardiovascular disease . They may also be involved in hearing impairment via cochlear damage induced by elevated sound levels , in ototoxicity of drugs such as cisplatin , and in congenital deafness in both animals and humans. ROS are also implicated in mediation of apoptosis or programmed cell death and ischaemic injury. Specific examples include stroke and heart attack . In general,

4795-491: A viable treatment for bladder disease. Proponents of body part replacement and cloning contend that the required biotechnologies are likely to appear earlier than other life-extension technologies. The use of human stem cells , particularly embryonic stem cells , is controversial. Opponents' objections generally are based on interpretations of religious teachings or ethical considerations. Proponents of stem cell research point out that cells are routinely formed and destroyed in

4932-589: A year in 2009. The use of such hormone products has not been proven to be effective or safe. During the process of aging , an organism accumulates damage to its macromolecules , cells , tissues , and organs . Specifically, aging is characterized as and thought to be caused by "genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis , deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence , stem cell exhaustion, and altered intercellular communication." Oxidation damage to cellular contents caused by free radicals

5069-413: Is hydrogen peroxide (H 2 O 2 ), which is converted from superoxide that leaks from the mitochondria. Catalase and superoxide dismutase ameliorate the damaging effects of hydrogen peroxide and superoxide, respectively, by converting these compounds into oxygen and hydrogen peroxide (which is later converted to water), resulting in the production of benign molecules . However, this conversion

5206-458: Is a contributor to senescence. In particular, the accumulation of oxidative damage may lead to cognitive dysfunction, as demonstrated in a study in which old rats were given mitochondrial metabolites and then given cognitive tests . Results showed that the rats performed better after receiving the metabolites, suggesting that the metabolites reduced oxidative damage and improved mitochondrial function. Accumulating oxidative damage can then affect

5343-501: Is a double-edged sword. On one hand, at low levels, ROS facilitates cancer cell survival since cell-cycle progression driven by growth factors and receptor tyrosine kinases (RTK) require ROS for activation and chronic inflammation, a major mediator of cancer, is regulated by ROS. On the other hand, a high level of ROS can suppress tumor growth through the sustained activation of cell-cycle inhibitor and induction of cell death as well as senescence by damaging macromolecules. In fact, most of

5480-584: Is a driving force behind apoptosis, but in even higher amounts, ROS can result in both apoptosis and necrosis, a form of uncontrolled cell death, in cancer cells. Numerous studies have shown the pathways and associations between ROS levels and apoptosis, but a newer line of study has connected ROS levels and autophagy. ROS can also induce cell death through autophagy, which is a self-catabolic process involving sequestration of cytoplasmic contents (exhausted or damaged organelles and protein aggregates) for degradation in lysosomes. Therefore, autophagy can also regulate

5617-536: Is a field of medicine that studies the treatment of existing disease in aging people, rather than the treatment of aging itself. There are numerous theories of aging, and no one theory has been entirely accepted. At their extremes, the wide spectrum of aging theories can be categorized into programmed theories – which imply that aging follows a biological timetable, and error theories – which suggest aging occurs due to cumulative damage experienced by organisms. Stochastic theories of aging are theories suggesting that aging

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5754-817: Is a hallmark of cancer cells. Both exogenous and endogenous ROS have been shown to enhance proliferation of cancer cells. The role of ROS in promoting tumor proliferation is further supported by the observation that agents with potential to inhibit ROS generation can also inhibit cancer cell proliferation. Although ROS can promote tumor cell proliferation, a great increase in ROS has been associated with reduced cancer cell proliferation by induction of G2/M cell cycle arrest; increased phosphorylation of ataxia telangiectasia mutated (ATM), checkpoint kinase 1 (Chk 1), Chk 2; and reduced cell division cycle 25 homolog c (CDC25). A cancer cell can die in three ways: apoptosis , necrosis , and autophagy . Excessive ROS can induce apoptosis through both

5891-596: Is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O 2 , which is central to fuel cells . ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations. ROS are not uniformly defined. All sources include superoxide, singlet oxygen, and hydroxyl radical. Hydrogen peroxide

6028-454: Is also known as the caspase cascade and is induced through mitochondrial damage which triggers the release of cytochrome c. DNA damage, oxidative stress, and loss of mitochondrial membrane potential lead to the release of the pro-apoptotic proteins mentioned above stimulating apoptosis. Mitochondrial damage is closely linked to apoptosis and since mitochondria are easily targeted there is potential for cancer therapy. The cytotoxic nature of ROS

6165-630: Is an overall increase in endogenous ROS, which when above a cellular tolerability threshold, may induce cell death. On the other hand, normal cells appear to have, under lower basal stress and reserve, a higher capacity to cope with additional ROS-generating insults than cancer cells do. Therefore, the elevation of ROS in all cells can be used to achieve the selective killing of cancer cells. Radiotherapy also relies on ROS toxicity to eradicate tumor cells. Radiotherapy uses X-rays, γ-rays as well as heavy particle radiation such as protons and neutrons to induce ROS-mediated cell death and mitotic failure. Due to

6302-460: Is associated only with infection by non-virulent pathogens and is an induced response dependent on increased mRNA transcription encoding enzymes. Superoxide dismutases (SOD) are a class of enzymes that catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen. In mammals and most chordates, three forms of superoxide dismutase are present. SOD1

6439-520: Is being conducted in university laboratories, and includes universities such as Harvard and UCLA . University researchers have made a number of breakthroughs in extending the lives of mice and insects by reversing certain aspects of aging. Theoretically, extension of maximum lifespan in humans could be achieved by reducing the rate of aging damage by periodic replacement of damaged tissues , molecular repair or rejuvenation of deteriorated cells and tissues, reversal of harmful epigenetic changes, or

6576-617: Is believed to contribute to aging as well. The longest documented human lifespan is 122 years 164 days, the case of Jeanne Calment , who according to records was born in 1875 and died in 1997, whereas the maximum lifespan of a wildtype mouse, commonly used as a model in research on aging, is about three years. Genetic differences between humans and mice that may account for these different aging rates include differences in efficiency of DNA repair , antioxidant defenses, energy metabolism , proteostasis maintenance, and recycling mechanisms such as autophagy . The average life expectancy in

6713-442: Is beneficial for cancer patient prognosis. Moreover, high inducers of ROS such as 2-deoxy-D-glucose and carbohydrate-based inducers of cellular stress induce cancer cell death more potently because they exploit the cancer cell's high avidity for sugars. ROS are critical in memory formation. ROS also have a central role in epigenetic DNA demethylation , which is relevant to learning and memory In mammalian nuclear DNA,

6850-489: Is bodily decline that results from an accumulation of elements, whether introduced to the body from the environment or resulting from cell metabolism . Mutation accumulation theory was first proposed by Peter Medawar in 1952 as an evolutionary explanation for biological ageing and the associated decline in fitness that accompanies it. The theory explains that, in the case where harmful mutations are only expressed later in life, when reproduction has ceased and future survival

6987-575: Is caused by small changes in the body over time and the body's failure to restore the system and mend the damages to the body. Cells and tissues are injured due to the accumulation of damage over time resulting in the diminished functioning of organs. The notion of accumulated damage was first introduced in 1882 by biologist Dr. August Weismann as the "wear and tear" theory. Wear and tear theories of aging began to be introduced yet in 19th century. They suggest that as an individual ages, body parts such as cells and organs wear out from continued use. Wearing of

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7124-441: Is commonly co-observed. Thus, once a more in-depth understanding of autophagic cell death is attained and its relation to ROS, this form of programmed cell death may serve as a future cancer therapy. Autophagy and apoptosis are distinct mechanisms for cell death brought on by high levels of ROS. Aautophagy and apoptosis, however, rarely act through strictly independent pathways. There is a clear connection between ROS and autophagy and

7261-453: Is determined by a "biological clock" via genetic information in the nucleus of the cell. Genes responsible for apoptosis provide an explanation for cell death, but are less applicable to death of an entire organism. An increase in cellular apoptosis may correlate to aging, but is not a 'cause of death'. Environmental factors and genetic mutations can influence gene expression and accelerate aging. More recently epigenetics have been explored as

7398-641: Is determined by the rate of aging for a species inherent in its genes and by environmental factors. Widely recognized methods of extending maximum lifespan in model organisms such as nematodes , fruit flies, and mice include caloric restriction , gene manipulation , and administration of pharmaceuticals. Another technique uses evolutionary pressures such as breeding from only older members or altering levels of extrinsic mortality. Some animals such as hydra , planarian flatworms , and certain sponges , corals , and jellyfish do not die of old age and exhibit potential immortality. The extension of life has been

7535-407: Is due to fear of overpopulation and possible effects on society. Biogerontologist Aubrey De Grey counters the overpopulation critique by pointing out that the therapy could postpone or eliminate menopause , allowing women to space out their pregnancies over more years and thus decreasing the yearly population growth rate. Moreover, the philosopher and futurist Max More argues that, given that

7672-451: Is extremely reactive and immediately removes electrons from any molecule in its path, turning that molecule into a free radical and thus propagating a chain reaction. However, hydrogen peroxide is actually more damaging to DNA than the hydroxyl radical, since the lower reactivity of hydrogen peroxide provides enough time for the molecule to travel into the nucleus of the cell, subsequently reacting with macromolecules such as DNA. In plants,

7809-404: Is generated from PSII, instead of PSI; QB is shown as the location for the generation of O 2 •-. The formation of ROS can be stimulated by a variety of agents such as pollutants, heavy metals , tobacco , smoke, drugs, xenobiotics , microplastics , or radiation. In plants, in addition to the action of dry abiotic factors , high temperature, interaction with other living beings can influence

7946-493: Is increasingly unlikely, then these mutations are likely to be unknowingly passed on to future generations. In this situation the force of natural selection will be weak, and so insufficient to consistently eliminate these mutations. Medawar posited that over time these mutations would accumulate due to genetic drift and lead to the evolution of what is now referred to as ageing. Free radicals are reactive molecules produced by cellular and environmental processes, and can damage

8083-465: Is known as oxidative stress . The production of ROS is strongly influenced by stress factor responses in plants, these factors that increase ROS production include drought, salinity, chilling, defense of pathogens, nutrient deficiency, metal toxicity and UV-B radiation. ROS are also generated by exogenous sources such as ionizing radiation generating irreversible effects in the development of tissues in both animals and plants. ROS are produced during

8220-454: Is located primarily in the cytoplasm, SOD2 in the mitochondria and SOD3 is extracellular. The first is a dimer (consists of two units), while the others are tetramers (four subunits). SOD1 and SOD3 contain copper and zinc ions, while SOD2 has a manganese ion in its reactive centre. The genes are located on chromosomes 21, 6, and 4, respectively (21q22.1, 6q25.3 and 4p15.3-p15.1). The SOD-catalysed dismutation of superoxide may be written with

8357-474: Is not 100% efficient, and residual peroxides persist in the cell. While ROS are produced as a product of normal cellular functioning, excessive amounts can cause deleterious effects. Memory capabilities decline with age, evident in human degenerative diseases such as Alzheimer's disease , which is accompanied by an accumulation of oxidative damage. Current studies demonstrate that the accumulation of ROS can decrease an organism's fitness because oxidative damage

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8494-429: Is not nearly as reactive as these species, but is readily activated and is thus included. Peroxynitrite and nitric oxide are reactive oxygen-containing species as well. In its fleeting existence, the hydroxyl radical reacts rapidly irreversibly with all organic compounds. Competing with its formation, superoxide is destroyed by the action of superoxide dismutases , enzymes that catalyze its disproportionation: In

8631-658: Is not only a childish desire to eat one's life and keep it; it is also an expression of a childish and narcissistic wish incompatible with devotion to posterity." John Harris, former editor-in-chief of the Journal of Medical Ethics, argues that as long as life is worth living, according to the person himself, we have a powerful moral imperative to save the life and thus to develop and offer life extension therapies to those who want them. Transhumanist philosopher Nick Bostrom has argued that any technological advances in life extension must be equitably distributed and not restricted to

8768-455: Is not unexpected, since mammals have evolved to live many times the worm's lifespan, and humans live nearly twice as long as the next longest-lived primate. From an evolutionary perspective, mammals and their ancestors have already undergone several hundred million years of natural selection favoring traits that could directly or indirectly favor increased longevity, and may thus have already settled on gene sequences that promote lifespan. Moreover,

8905-490: Is ongoing. DNA damage has been one of the major causes in diseases related to aging. The stability of the genome is defined by the cells machinery of repair, damage tolerance, and checkpoint pathways that counteracts DNA damage. One hypothesis proposed by physicist Gioacchino Failla in 1958 is that damage accumulation to the DNA causes aging. The hypothesis was developed soon by physicist Leó Szilárd . This theory has changed over

9042-445: Is present in mitochondria, a cell undergoes apoptosis or programmed cell death. In addition, ROS are produced in immune cell signaling via the NOX pathway. Phagocytic cells such as neutrophils , eosinophils , and mononuclear phagocytes produce ROS when stimulated. In chloroplasts , the carboxylation and oxygenation reactions catalyzed by rubisco ensure that the functioning of

9179-705: Is the concept of extending the human lifespan , either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled biological limit of around 125 years . Several researchers in the area, along with "life extensionists", " immortalists ", or " longevists " (those who wish to achieve longer lives themselves), postulate that future breakthroughs in tissue rejuvenation , stem cells , regenerative medicine , molecular repair, gene therapy , pharmaceuticals, and organ replacement (such as with artificial organs or xenotransplantations ) will eventually enable humans to have indefinite lifespans through complete rejuvenation to

9316-526: Is the primary cause of aging comes from study of Poly ADP ribose polymerases (PARPs). PARPs are enzymes that are activated by DNA strand breaks and play a role in DNA base excision repair. Burkle et al. reviewed evidence that PARPs, and especially PARP-1, are involved in maintaining mammalian longevity. The life span of 13 mammalian species correlated with poly(ADP ribosyl)ation capability measured in mononuclear cells. Furthermore, lymphoblastoid cell lines from peripheral blood lymphocytes of humans over age 100 had

9453-399: Is the primary cause of aging is based, in part, on evidence in human and mouse that inherited deficiencies in DNA repair genes often cause accelerated aging. There is also substantial evidence that DNA damage accumulates with age in mammalian tissues, such as those of the brain, muscle, liver and kidney (see DNA damage theory of aging and DNA damage (naturally occurring) ). One expectation of

9590-451: Is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases. Removal of senescent cells with senolytics has been proposed as a method of enhancing immunity during aging. Senolytics eliminate senescent cells whereas senomorphics – with candidates such as Apigenin , Everolimus and Rapamycin – modulate properties of senescent cells without eliminating them, suppressing phenotypes of senescence, including

9727-548: The Age of Enlightenment . He cites Francis Bacon (1561–1626) as an advocate of using science and reason to extend human life, noting Bacon's novel New Atlantis , wherein scientists worked toward delaying aging and prolonging life. Robert Boyle (1627–1691), founding member of the Royal Society , also hoped that science would make substantial progress with life extension, according to Hughes, and proposed such experiments as "to replace

9864-659: The Methuselah Foundation , which gives financial grants to anti-aging research projects. In 2009, de Grey and several others founded the SENS Research Foundation , a California-based scientific research organization which conducts research into aging and funds other anti-aging research projects at various universities. In 2013, Google announced Calico , a new company based in San Francisco that will harness new technologies to increase scientific understanding of

10001-650: The SASP . Senomorphic effects may be one major effect mechanism of a range of prolongevity drug candidates. Such candidates are however typically not studied for just one mechanism, but multiple. There are biological databases of prolongevity drug candidates under research as well as of potential gene/protein targets. These are enhanced by longitudinal cohort studies , electronic health records , computational (drug) screening methods, computational biomarker-discovery methods and computational biodata-interpretation/ personalized medicine methods. Besides rapamycin and senolytics,

10138-436: The connective tissue , kidney diseases, and enlargement of the heart are connected to the cross-linking of proteins. Crosslinking of DNA can induce replication errors, and this leads to deformed cells and increases the risk of cancer . Genetic theories of aging propose that aging is programmed within each individual's genes. According to this theory, genes dictate cellular longevity. Programmed cell death, or apoptosis ,

10275-532: The drug-repurposing candidates studied most extensively include metformin , acarbose , spermidine and NAD+ enhancers. Reactive oxygen species In chemistry and biology , reactive oxygen species ( ROS ) are highly reactive chemicals formed from diatomic oxygen ( O 2 ), water , and hydrogen peroxide . Some prominent ROS are hydroperoxide (O 2 H), superoxide (O 2 ), hydroxyl radical (OH ), and singlet oxygen . ROS are pervasive because they are readily produced from O 2 , which

10412-445: The electron transport chain . In the electron transport chain, electrons are passed through a series of proteins via oxidation-reduction reactions, with each acceptor protein along the chain having a greater reduction potential than the previous. The last destination for an electron along this chain is an oxygen molecule. In normal conditions, the oxygen is reduced to produce water; however, in about 0.1–2% of electrons passing through

10549-420: The free radical theory of aging , oxidative damage initiated by reactive oxygen species is a major contributor to the functional decline that is characteristic of aging. While studies in invertebrate models indicate that animals genetically engineered to lack specific antioxidant enzymes (such as SOD), in general, show a shortened lifespan (as one would expect from the theory), the converse manipulation, increasing

10686-473: The 'healthspan' over which an individual lives without serious illness. The approach of biogerontologists is that aging is disease per se and should be treated directly, with the ultimate goal of having the probability of individual dying be independent of their age (if external factors are held constant). This is in contrast to the opinion that maximum life span can not, or should not, be altered. Biogerontology should not be confused with geriatrics , which

10823-588: The Nobel Prize winning biologist Elie Metchnikoff (1845-1916) -- the author of the cell theory of immunity and vice director of Institut Pasteur in Paris, and Charles-Édouard Brown-Séquard (1817-1894) -- the president of the French Biological Society and one of the founders of modern endocrinology. Sociologist James Hughes claims that science has been tied to a cultural narrative of conquering death since

10960-484: The US President's Council on Bioethics from 2001 to 2005) has questioned whether potential exacerbation of overpopulation problems would make life extension unethical. He states his opposition to life extension with the words: "simply to covet a prolonged life span for ourselves is both a sign and a cause of our failure to open ourselves to procreation and to any higher purpose ... [The] desire to prolong youthfulness

11097-555: The United States of America, it would also increase the regulation of the anti-aging market by the Food and Drug Administration (FDA). Anti-aging now falls under the regulations for cosmetic medicine which are less tight than those for drugs. A senolytic (from the words senescence and -lytic , "destroying") is among a class of small molecules under basic research to determine if they can selectively induce death of senescent cells and improve health in humans. A goal of this research

11234-416: The aging process." 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 machines, including ones operating within cells and utilizing as yet hypothetical molecular computers , in his 1986 book Engines of Creation . Raymond Kurzweil ,

11371-429: The beginning of the modern period in this endeavor can be traced to the end of the 19th – beginning of the 20th century, to the so-called " fin-de-siècle " (end of the century) period, denoted as an "end of an epoch" and characterized by the rise of scientific optimism and therapeutic activism, entailing the pursuit of life extension (or life-extensionism). Among the foremost researchers of life extension at this period were

11508-550: The biological system and are required to drive regulatory pathways. Under normal physiological conditions, cells control ROS levels by balancing the generation of ROS with their elimination by scavenging systems. But under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids and DNA, leading to fatal lesions in the cell that contribute to carcinogenesis. Cancer cells exhibit greater ROS stress than normal cells do, partly due to oncogenic stimulation, increased metabolic activity and mitochondrial malfunction. ROS

11645-487: The biology of aging. It is led by Arthur D. Levinson , and its research team includes scientists such as Hal V. Barron , David Botstein , and Cynthia Kenyon . In 2014, biologist Craig Venter founded Human Longevity Inc., a company dedicated to scientific research to end aging through genomics and cell therapy. They received funding with the goal of compiling a comprehensive human genotype, microbiome, and phenotype database. Aside from private initiatives, aging research

11782-520: The blood of the old with the blood of the young". Biologist Alexis Carrel (1873–1944) was inspired by a belief in indefinite human lifespan that he developed after experimenting with cells , says Hughes. Regulatory and legal struggles between the Food and Drug Administration (FDA) and the Life Extension organization included seizure of merchandise and court action. In 1991, Saul Kent and Bill Faloon ,

11919-522: The body can be attributable to internal or external causes that eventually lead to an accumulation of insults which surpasses the capacity for repair. Due to these internal and external insults, cells lose their ability to regenerate, which ultimately leads to mechanical and chemical exhaustion. Some insults include chemicals in the air, food, or smoke. Other insults may be things such as viruses, trauma, free radicals, cross-linking , and high body temperature. Accumulation theories of aging suggest that aging

12056-580: The cell is no longer viable. The extensive amount of ROS and mitochondrial damage may also signal for apoptosis. The balance of autophagy within the cell and the crosstalk between autophagy and apoptosis mediated by ROS is crucial for a cell's survival. This crosstalk and connection between autophagy and apoptosis could be a mechanism targeted by cancer therapies or used in combination therapies for highly resistant cancers. After growth factor stimulation of RTKs, ROS can trigger activation of signaling pathways involved in cell migration and invasion such as members of

12193-413: The cell wall. This prevents the spread of the pathogen to other parts of the plant, essentially forming a net around the pathogen to restrict movement and reproduction. In the mammalian host, ROS is induced as an antimicrobial defense. To highlight the importance of this defense, individuals with chronic granulomatous disease who have deficiencies in generating ROS, are highly susceptible to infection by

12330-515: The cell's health in times of oxidative stress. Autophagy can be induced by ROS levels through many pathways in the cell in an attempt to dispose of harmful organelles and prevent damage, such as carcinogens, without inducing apoptosis. Autophagic cell death can be prompted by the over expression of autophagy where the cell digests too much of itself in an attempt to minimize the damage and can no longer survive. When this type of cell death occurs, an increase or loss of control of autophagy regulating genes

12467-403: The chain (this number derives from studies in isolated mitochondria, though the exact rate in live organisms is yet to be fully agreed upon), oxygen is instead prematurely and incompletely reduced to give the superoxide radical ( O 2 ), most well documented for Complex I and Complex III . Another source of ROS production in animal cells is the electron transfer reactions catalyzed by

12604-410: The changes caused by these genes activating can be lethal. It is a statistical certainty that we possess more lethal genes that activate in later life than in early life. Therefore, to extend life, we should be able to prevent these genes from switching on, and we should be able to do so by "identifying changes in the internal chemical environment of a body that take place during aging... and by simulating

12741-529: The chemotherapeutic and radiotherapeutic agents kill cancer cells by augmenting ROS stress. The ability of cancer cells to distinguish between ROS as a survival or apoptotic signal is controlled by the dosage, duration, type, and site of ROS production. Modest levels of ROS are required for cancer cells to survive, whereas excessive levels kill them. Metabolic adaptation in tumours balances the cells' need for energy with equally important need for macromolecular building blocks and tighter control of redox balance. As

12878-426: The dual role of ROS, both prooxidant and antioxidant-based anticancer agents have been developed. However, modulation of ROS signaling alone seems not to be an ideal approach due to adaptation of cancer cells to ROS stress, redundant pathways for supporting cancer growth and toxicity from ROS-generating anticancer drugs. Combinations of ROS-generating drugs with pharmaceuticals that can break the redox adaptation could be

13015-486: The efficiency of mitochondria and further increase the rate of ROS production. The accumulation of oxidative damage and its implications for aging depends on the particular tissue type where the damage is occurring. Additional experimental results suggest that oxidative damage is responsible for age-related decline in brain functioning. Older gerbils were found to have higher levels of oxidized protein in comparison to younger gerbils. Treatment of old and young mice with

13152-560: The electron transport chain (ETC) occurs in an environment rich in O 2 . The leakage of electrons in the ETC will inevitably produce ROS within the chloroplasts. ETC in photosystem I (PSI) was once believed to be the only source of ROS in chloroplasts. The flow of electrons from the excited reaction centers is directed to the NADP and these are reduced to NADPH, and then they enter the Calvin cycle and reduce

13289-413: The elements of the cell such as the cell membrane and DNA and cause irreversible damage. The free-radical theory of aging proposes that this damage cumulatively degrades the biological function of cells and impacts the process of aging. The idea that free radicals are toxic agents was first proposed by Rebeca Gerschman and colleagues in 1945, but came to prominence in 1956, when Denham Harman proposed

13426-474: The energy needed to fuel biological functions is produced in the mitochondria via the electron transport chain . Reactive oxygen species (ROS) with the potential to cause cellular damage are produced along with the release of energy. ROS can damage lipids, DNA , RNA , and proteins, which, in theory, contributes to the physiology of aging . ROS are produced as a normal product of cellular metabolism . In particular, one major contributor to oxidative damage

13563-506: The energy of the reactive peroxides to a sulfur-containing tripeptide called glutathione . The sulfur contained in these enzymes acts as the reactive center, carrying reactive electrons from the peroxide to the glutathione. Peroxiredoxins also degrade H 2 O 2 , within the mitochondria, cytosol, and nucleus. Effects of ROS on cell metabolism are well documented in a variety of species. These include not only roles in apoptosis (programmed cell death) but also positive effects such as

13700-400: The enhancement of enzyme telomerase activity. Research geared towards life extension strategies in various organisms is currently under way at a number of academic and private institutions. Since 2009, investigators have found ways to increase the lifespan of nematode worms and yeast by 10-fold; the record in nematodes was achieved through genetic engineering and the extension in yeast by

13837-453: The expression of a gene. A major enzyme involved in demethylating 5mCpG is TET1 . However, TET1 is only able to act on 5mCpG if an ROS has first acted on the guanine to form 8-hydroxy-2'-deoxyguanosine (8-OHdG), resulting in a 5mCp-8-OHdG dinucleotide . However, TET1 is only able to act on the 5mC part of the dinucleotide when the base excision repair enzyme OGG1 binds to the 8-OHdG lesion without immediate excision. Adherence of OGG1 to

13974-406: The expression of nucleus genes leading to chlorosis and programmed cell death . In cases of biotic stress, the generation of ROS occurs quickly and weakly initially and then becomes more solid and lasting. The first phase of ROS accumulation is associated with plant infection and is probably independent of the synthesis of new ROS-generating enzymes . However, the second phase of ROS accumulation

14111-614: The expression of various tumor suppressor genes such as p53, retinoblastoma gene (Rb), and phosphatase and tensin homolog (PTEN). ROS-related oxidation of DNA is one of the main causes of mutations, which can produce several types of DNA damage, including non-bulky (8-oxoguanine and formamidopyrimidine) and bulky (cyclopurine and etheno adducts) base modifications, abasic sites, non-conventional single-strand breaks, protein-DNA adducts, and intra/interstrand DNA crosslinks. It has been estimated that endogenous ROS produced via normal cell metabolism modify approximately 20,000 bases of DNA per day in

14248-579: The extrinsic and intrinsic pathways. In the extrinsic pathway of apoptosis, ROS are generated by Fas ligand as an upstream event for Fas activation via phosphorylation, which is necessary for subsequent recruitment of Fas-associated protein with death domain and caspase 8 as well as apoptosis induction. In the intrinsic pathway, ROS function to facilitate cytochrome c release by activating pore-stabilizing proteins (Bcl-2 and Bcl-xL) as well as inhibiting pore-destabilizing proteins (Bcl-2-associated X protein, Bcl-2 homologous antagonist/killer). The intrinsic pathway

14385-758: The fastest possible and at the same time soft transition of society to the next step – life without aging and with radical life extension, and to provide access to such technologies to most currently living people. Some tech innovators and Silicon Valley entrepreneurs have invested heavily into anti-aging research. This includes Jeff Bezos (founder of Amazon ), Larry Ellison (founder of Oracle ), Peter Thiel (former PayPal CEO), Larry Page (co-founder of Google ), Peter Diamandis , Sam Altman (CEO of OpenAI , invested in Retro Biosciences ), and Brian Armstrong (founder of Coinbase and NewLimit), Bryan Johnson (Founder of Kernel ). Leon Kass (chairman of

14522-532: The final electron acceptor, CO 2 . In cases where there is an ETC overload, part of the electron flow is diverted from ferredoxin to O 2 , forming the superoxide free radical (by the Mehler reaction ). In addition, electron leakage to O 2 can also occur from the 2Fe-2S and 4Fe-4S clusters in the PSI ETC. However, PSII also provides electron leakage locations (QA, QB) for O 2 -producing O 2 -. Superoxide (O 2 -)

14659-451: The following half-reactions: where M =  Cu ( n = 1 ); Mn ( n = 2 ); Fe ( n = 2 ); Ni ( n = 2 ). In this reaction the oxidation state of the metal cation oscillates between n and n + 1 . Catalase , which is concentrated in peroxisomes located next to mitochondria, reacts with the hydrogen peroxide to catalyze the formation of water and oxygen. Glutathione peroxidase reduces hydrogen peroxide by transferring

14796-449: The former being predominantly used. Cancer cells with elevated ROS levels depend heavily on the antioxidant defense system. ROS-elevating drugs further increase cellular ROS stress level, either by direct ROS-generation (e.g. motexafin gadolinium, elesclomol) or by agents that abrogate the inherent antioxidant system such as SOD inhibitor (e.g. ATN-224, 2-methoxyestradiol) and GSH inhibitor (e.g. PEITC, buthionine sulfoximine (BSO)). The result

14933-444: The free-radical theory of aging and even demonstrated that free radical reactions contribute to the degradation of biological systems. Oxidative damage of many types accumulate with age, such as oxidative stress that oxygen-free radicals, because the free radical theory of aging argues that aging results from the damage generated by reactive oxygen species (ROS). ROS are small, highly reactive, oxygen-containing molecules that can damage

15070-761: The gut. The manner in which ROS defends the host from invading microbe is not fully understood. One of the more likely modes of defense is damage to microbial DNA. Studies using Salmonella demonstrated that DNA repair mechanisms were required to resist killing by ROS. A role for ROS in antiviral defense mechanisms has been demonstrated via Rig-like helicase-1 and mitochondrial antiviral signaling protein. Increased levels of ROS potentiate signaling through this mitochondria-associated antiviral receptor to activate interferon regulatory factor (IRF)-3, IRF-7, and nuclear factor kappa B (NF-κB), resulting in an antiviral state. Respiratory epithelial cells induce mitochondrial ROS in response to influenza infection. This induction of ROS led to

15207-470: The harmful effects of reactive oxygen species on the cell are the damage of DNA or RNA, oxidation of polyunsaturated fatty acids in lipids ( lipid peroxidation ), oxidation of amino acids in proteins, and oxidative deactivation of specific enzymes by oxidation co-factors. When a plant recognizes an attacking pathogen, one of the first induced reactions is to rapidly produce superoxide ( O 2 ) or hydrogen peroxide ( H 2 O 2 ) to strengthen

15344-646: The immune system weakens as an organism ages. This makes the organism unable to fight infections and less able to destroy old and neoplastic cells . This leads to aging and will eventually lead to death. This theory of aging was developed by Roy Walford in 1969. According to Walford, incorrect immunological procedures are the cause of the process of aging. Walford, who stated that his optimized health regime would allow him to live to 120, died of amytrophic lateral sclerosis at age 79. attribution contains material copied from Gerontology . Biomedical gerontology Chemical Neurological Life extension

15481-441: The induction of host defence genes and mobilization of ion transporters . This implicates them in control of cellular function. In particular, platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury . These also provide a link to the adaptive immune system via the recruitment of leukocytes . Reactive oxygen species are implicated in cellular activity to

15618-469: The induction of type III interferon and the induction of an antiviral state, limiting viral replication. In host defense against mycobacteria, ROS play a role, although direct killing is likely not the key mechanism; rather, ROS likely affect ROS-dependent signalling controls, such as cytokine production, autophagy, and granuloma formation. Reactive oxygen species are also implicated in activation, anergy and apoptosis of T cells . In aerobic organisms

15755-614: The levels of antioxidant enzymes, has yielded inconsistent effects on lifespan (though some studies in Drosophila do show that lifespan can be increased by the overexpression of MnSOD or glutathione biosynthesizing enzymes). Also contrary to this theory, deletion of mitochondrial SOD2 can extend lifespan in Caenorhabditis elegans . In mice, the story is somewhat similar. Deleting antioxidant enzymes, in general, yields shorter lifespan, although overexpression studies have not (with some exceptions) consistently extended lifespan. Study of

15892-508: The longest extension of life caused by a single gene manipulation was roughly 50% in mice and 10-fold in nematode worms. In July 2020 scientists, using public biological data on 1.75 m people with known lifespans overall, identify 10 genomic loci which appear to intrinsically influence healthspan , lifespan, and longevity – of which half have not been reported previously at genome-wide significance and most being associated with cardiovascular disease – and identify haem metabolism as

16029-460: The mitochondrial P450 systems in steroidogenic tissues. These P450 systems are dependent on the transfer of electrons from NADPH to P450. During this process, some electrons "leak" and react with O 2 producing superoxide. To cope with this natural source of ROS, the steroidogenic tissues, ovary and testis, have a large concentration of antioxidants such as vitamin C (ascorbate) and β-carotene and anti-oxidant enzymes. If too much damage

16166-532: The mitogen activated protein kinase (MAPK) family – extracellular regulated kinase (ERK), c-jun NH-2 terminal kinase (JNK) and p38 MAPK. ROS can also promote migration by augmenting phosphorylation of the focal adhesion kinase (FAK) p130Cas and paxilin. Both in vitro and in vivo, ROS have been shown to induce transcription factors and modulate signaling molecules involved in angiogenesis (MMP, VEGF) and metastasis (upregulation of AP-1, CXCR4, AKT and downregulation of PTEN). Experimental and epidemiologic research over

16303-482: The past several years has indicated close associations among ROS, chronic inflammation, and cancer. ROS induces chronic inflammation by the induction of COX-2, inflammatory cytokines (TNFα, interleukin 1 (IL-1), IL-6), chemokines (IL-8, CXCR4) and pro-inflammatory transcription factors (NF-κB). These chemokines and chemokine receptors, in turn, promote invasion and metastasis of various tumor types. Both ROS-elevating and ROS-eliminating strategies have been developed with

16440-490: 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 . Replacement of biological (susceptible to diseases) organs with mechanical ones could extend life. This is the goal of the 2045 Initiative . Cryonics is the low-temperature freezing (usually at −196 °C or −320.8 °F or 77.1 K) of

16577-537: The portrayal of aging as a disease. For example, Leonard Hayflick , who determined that fibroblasts are limited to around 50 cell divisions, reasons that aging is an unavoidable consequence of entropy . Hayflick and fellow biogerontologists Jay Olshansky and Bruce Carnes have strongly criticized the anti-aging industry in response to what they see as unscrupulous profiteering from the sale of unproven anti-aging supplements . Research by Sobh and Martin (2011) suggests that people buy anti-aging products to obtain

16714-421: The possibility of growing human body parts on mice. Complex biological structures, such as mammalian joints and limbs, have not yet been replicated. Dog and primate brain transplantation experiments were conducted in the mid-20th century but failed due to rejection and the inability to restore nerve connections. As of 2006, the implantation of bio-engineered bladders grown from patients' own cells has proven to be

16851-423: The potential role of embryonic stem cells in life extension. Other modern life extensionists include writer Gennady Stolyarov , who insists that death is "the enemy of us all, to be fought with medicine, science, and technology"; transhumanist philosopher Zoltan Istvan , who proposes that the "transhumanist must safeguard one's own existence above all else"; futurist George Dvorsky , who considers aging to be

16988-559: The principals of the organization, were jailed for four hours and were released on $ 850,000 bond each. After 11 years of legal battles, Kent and Faloon convinced the US Attorney's Office to dismiss all criminal indictments brought against them by the FDA. In 2003, Doubleday published "The Immortal Cell: One Scientist's Quest to Solve the Mystery of Human Aging," by Michael D. West . West emphasised

17125-442: The processes of respiration and photosynthesis in organelles such as mitochondria , peroxisomes and chloroplasts . During the respiration process the mitochondria convert energy for the cell into a usable form, adenosine triphosphate (ATP). The process of ATP production in the mitochondria, called oxidative phosphorylation , involves the transport of protons (hydrogen ions) across the inner mitochondrial membrane by means of

17262-403: The production of ROS occurs during events of abiotic stress that lead to a reduction or interruption of metabolic activity. For example, the increase in temperature, drought are factors that limit the availability of CO 2 due to stomatal closure, increasing the production of ROS, such as O 2 ·- and O 2 in chloroplasts. The production of O 2 in chloroplasts can cause reprogramming of

17399-586: The production of ROS. Ionizing radiation can generate damaging intermediates through the interaction with water, a process termed radiolysis . Since water comprises 55–60% of the human body, the probability of radiolysis is quite high under the presence of ionizing radiation. In the process, water loses an electron and becomes highly reactive. Then through a three-step chain reaction, water is sequentially converted to hydroxyl radical ( OH), hydrogen peroxide (H 2 O 2 ), superoxide radical ( O 2 ), and ultimately oxygen (O 2 ). The hydroxyl radical

17536-604: The reducing power of NADPH to maintain their activities. Most risk factors associated with cancer interact with cells through the generation of ROS. ROS then activate various transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein-1 (AP-1), hypoxia-inducible factor-1α and signal transducer and activator of transcription 3 (STAT3), leading to expression of proteins that control inflammation; cellular transformation; tumor cell survival; tumor cell proliferation; and invasion, angiogenesis as well as metastasis. And ROS also control

17673-736: The same effect on the aging process as a CR diet, which are known as caloric restriction mimetic drugs, such as rapamycin and metformin . Sirtuin activating polyphenols , such as resveratrol and pterostilbene , and flavonoids , such as quercetin and fisetin , as well as oleic acid are dietary supplements that have also been studied in this context. Other common supplements with less clear biological pathways to target aging include lipoic acid , senolytics , and coenzyme Q10 . While agents such as these have some limited laboratory evidence of efficacy in animals, there are no studies to date in humans for drugs that may promote life extension, mainly because research investment remains at

17810-459: The superficial chemical properties of a young body". Some life extensionists suggest that therapeutic cloning and stem cell research could one day provide a way to generate cells, body parts, or even entire bodies (generally referred to as reproductive cloning ) that would be genetically identical to a prospective patient. In 2008, the US Department of Defense announced a program to research

17947-464: The theory (that DNA damage is the primary cause of aging) is that among species with differing maximum life spans, the capacity to repair DNA damage should correlate with lifespan. The first experimental test of this idea was by Hart and Setlow who measured the capacity of cells from seven different mammalian species to carry out DNA repair. They found that nucleotide excision repair capability increased systematically with species longevity. This correlation

18084-529: The use of stem cells and tissue engineering , telomere -lengthening machinery, allotopic expression of mitochondrial proteins, targeted ablation of cells, immunotherapeutic clearance, and novel lysosomal hydrolases . While some biogerontologists find these ideas "worthy of discussion", others contend that the alleged benefits are too speculative given the current state of technology, referring to it as "fantasy rather than science". Genome editing , in which nucleic acid polymers are delivered as

18221-458: The very notion of a "life-extension factor" that could apply across taxa presumes a linear response rarely seen in biology." There are numerous chemicals intended to slow the aging process under study in animal models . One type of research is related to the observed effects of a calorie restriction (CR) diet, which has been shown to extend lifespan in some animals. Based on that research, there have been attempts to develop drugs that will have

18358-495: The worldwide population growth rate is slowing down and is projected to eventually stabilize and begin falling, superlongevity would be unlikely to contribute to overpopulation. A Spring 2013 Pew Research poll in the United States found that 38% of Americans would want life extension treatments, and 56% would reject it. However, it also found that 68% believed most people would want it and that only 4% consider an "ideal lifespan" to be more than 120 years. The median "ideal lifespan"

18495-462: The years as new research has discovered new types of DNA damage and mutations, and several theories of aging argue that DNA damage with or without mutations causes aging. DNA damage is distinctly different from mutation , although both are types of error in DNA . DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of standard base pairs. The theory that DNA damage

18632-434: Was 91 years of age and the majority of the public (63%) viewed medical advances aimed at prolonging life as generally good. 41% of Americans believed that radical life extension (RLE) would be good for society, while 51% said they believed it would be bad for society. One possibility for why 56% of Americans claim they would reject life extension treatments may be due to the cultural perception that living longer would result in

18769-414: Was striking and stimulated a series of 11 additional experiments in different laboratories over succeeding years on the relationship of nucleotide excision repair and life span in mammalian species (reviewed by Bernstein and Bernstein). In general, the findings of these studies indicated a good correlation between nucleotide excision repair capacity and life span. Further support for the theory that DNA damage

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