The mitochondrial theory of aging by james south ma. Marasco, danafarber cancer institute chromosome bands. The role of the detoxifying enzyme superoxide dismutase in staving off aging, cancer, and dementia and what we can do to boost its activity. A midlife crisis for the mitochondrial free radical theory. Aging and the mitochondria antiaging articles magazine. The mitochondrial theory of aging and its relationship to reactive oxygen species. Also referred to as developmental theory personality is well developed by the time one reaches old age and tends to remain consistent across the life span. Cefalu, md, ms keywords aging telomeres free radicals autoimmune theory of aging geneticdevelopmental theory of aging theories of aging several theories may explain the normal aging process, either alone or in combination with other theories table 1. Most of the energyproducing reactions occur at the inner membrane, which is made of lipids fats studded with proteins. As people age, they are less concerned with their physical bodies, material possessions, meaningless relationships, and selfinterests and instead desire a life of more significance and a greater. In previous posts we discussed the free radial theory of aging and the neuroendocrine theory of aging.
Theories and mechanisms of aging office of geriatrics and. Another popular theory of aging that has gained momentum in the last 10. Every cell in the body has hundreds or thousands of mitochondria, the sites of the highenergy chemistry that produces ros as toxic waste. A free radical is any atom or molecule that has a single unpaired electron in an outer shell. Looking for potential candidates to progressive accumulation of damage over a lifetime, it seems reasonable to exclude rna, proteins and other cellular macromolecules with a rapid turned over. According to this theory, the aging process is mediated by a vicious cycle of events ultimately leading to cellular senescence. The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtdna mutations. Crosslinkage theory the crosslinking theory, also referred to as the glycosylation theory of aging, was proposed by johan bjorksten in 1942. In 1971, the telomere theory of aging was proposed by russian scientist a.
Aging by program, where biological clocks act through hormones to control the pace of aging. The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtdna mutations lawrence a. Oxidative stress and the mitochondrial theory of aging in. A popular theory a generation back sought to trace aging to oxidative damage originating in the mitochondria.
A midlife crisis for the mitochondrial free radical theory of aging. Purchase the mitochondrion in aging and disease, volume 127 1st edition. According to the membrane theory of aging, agerelated decline in membrane function leads to inefficient communication through membrane and accumulation of toxic compound in the cellular membrane. The gene theory states that aging is programmed due to one or more harmful genes within each organism. Empirical research, previous literature culturalsocial historical climate theory producers own values and interests also usually the result of a culturalsocial historical climate aging theories.
Olovnikov on the ground of data obtained by american researcher l. Martin department of pathology, university of washington, seattle, wa 98195. To address that problem, many antiaging studies and supplements are geared toward reducing the effects of free radicals. According to this theory, an accumulation of crosslinked proteins damages cells and tissues, slowing down bodily processes resulting in aging. Today, the importance of mitochondrial biology linking basic aspects of aging and the pathogenesis of agerelated diseases remains strong, yet the emphasis has changed.
Each of these theories consists of different subtheories that are. Its a little like charging our ipod battery over and over again. The mitochondrial free radical theory of aging molecular biology intelligence unit 9 molecular biology intelligence unit. Despite compelling evidence that supports the mitochondrial theory of aging in some tissues, data regarding aging skeletal muscle are inconsistent. Central to this vicious cycle is an increase in oxidative stress, mediated by an increased production of. In aged subjects, mitochondria are characterized by impaired function such as lowered oxidative capacity, reduced oxidative. As mitochondria are the principle source of intracellular reactive oxygen species ros, this hypothesis suggested a central role for the mitochondrion in normal mammalian aging. Proponents of nonprogrammed aging arguing against nonindividualbenefit theories or associated programmed aging theories therefore have to show that all of the nonindividual benefit theories and all of the associated programmed aging theories are utterly invalid to the point where none of them could provide an even minute benefit to a purposely.
In acknowledging that at least in theory, aging might occasionally be adaptive, however, the high barriers to validating actual instances of adaptive ageing are made clear 1. This results in a progressive loss of the amount of mitochondria capable of providing sufficient energy for the optimal functioning of the cells. This theory continued to grow and gain acceptance and by the beginning of the next decade. Programmed and nonprogrammed theories of aging springerlink. Some proponents of nonprogrammed aging still contend that their nonprogrammed theories are superior despite the new mechanics concepts. Theories and mechanisms of aging ohio state university. Bickmore, mrc human genetics unit and jeffrey craig, universitat heidelberg hormonal control of postembryonic.
Dec 27, 2005 in normal aging, a role for the emergence of mutator polg molecules also needs to be considered, and it will be important to determine whether pol. The free radical theory of aging has evolved into the mitochondrial theory of aging this theory states that over time mitochondria accumulate damage to their own genetic material. The mitochondrial theory of aging has two varieties. Among the numerous theories that explain the process of aging, the mitochondrial theory of aging has received the most attention. A recent theory that suggest aging entails a transition from a rational, materialistic metaperspective to a cosmic and transcendence vision. Mitochondrial theory of aging yields startling results us. Aging as a particular case of phenoptosis, the programmed. A few years ago it was hardly possible to find the latter statement in an article written by the most famous proponents of nonprogrammed aging.
A new look at the free radical theory of aging natural. Pages in category theories of nonbiological aging the following 4 pages are in this category, out of 4 total. The first is one of the variants of the free radical theory of aging. There are several theories of aging, and its most likely that these various theories all contribute to the aging process. If we were building a house or other complex structure, we would need a plan and a schedule. Harmans mitochondrial free radical theory of aging postulated that somatic mitochondrial dna mutations that accumulate over the life span cause excessive production of reactive oxygen species that damage macromolecules and impair cell and. Pdf the mitochondrial free radical theory of aging mfrta proposes that mitochondrial free radicals, produced as byproducts during normal. Mitochondrial theory of aging the agerelated physiological decline seems to be due to the accumulation of defects in the several metabolic pathways. Gene theory, which considers aging to be the result of a sequential switching on and off of certain genes, with senescence being defined as the time when ageassociated deficits are manifested. Denham harman first proposed the free radical theory of aging in the 1950s, and in the 1970s extended the idea to implicate. While a few free radicals such as melanin are not chemically reactive, most biologically relevant free radicals are highly reactive. If mitochondrial ros are involved in the aging process, it seems very likely it will be via highly specific and regulated cellular processes and not.
Although both mitochondrial and nuclear dna damage can contribute to aging, nuclear dna is the main subject of this analysis. Prior to darwin there was no reason to suspect that life span had an origin that was different from that of any other organism. Theory of aging free download as powerpoint presentation. The mitochondrial free radical theory of aging aubrey d. Aging and the mitochondria details dallas clouatre, phd. The mitochondrial free radical theory of aging molecular.
The mitochondrial free radical theory of aging cellfood. But more and more research points to the mitochondrial free radical theory of aging, that as people age, oxidative damage piles up in individual cells such that the energygeneration system inside some cells stops working properly. Increased understanding of these interactions will likely yield new approaches to slow, or. Aging is the process by which the body becomes less capable of repairing and rejuvenating itself, which results in all of these unpleasant diseases. Defects in dna repair seem to be directly related to aging. The gene theory suggests that human life span is an inherited trait. The free radical theory of aging is almost 60 years old. The mta was further refined and developed in 1980 by jaime miquel 2. The mitochondrial decline theory of aging was first proposed in 1972 by denham harman.
Free radical theory somatic mutation theory it is believed that certain chemical compounds in the body does damage which accumulates to produce aging. Aug 23, 20 the mitochondrial decline theory of aging was first proposed in 1972 by denham harman. The dna damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring dna damages. It has been supported by the observation that mitochondrial function declines and mtdna mutation increases in tissue cells in an agedependent manner. Michel in 1980 and was developed in the works of a. The free radical theory of aging frta states that organisms age because cells accumulate free radical damage over time. Nonetheless, there are a number of observations that suggest that the cellular effects of ros, with regard to inducing senescence, do not unequivocally transfer to. Damage in this context is a dna alteration that has an abnormal structure. The theories to explain the aging could be put into two groups. Damage theory is the idea that external or environmental forces gradually damage cells and organs, leading to aging and death.
Mitochondrial dna and aging clinical science portland press. To address that problem, many anti aging studies and supplements are geared toward reducing the effects of free radicals. Twenty or ten years ago, antioxidants and the free radical theory of aging largely dominated thinking. Mitochondrial theory of aging, a variant of free radical theory of aging, proposes that accumulation of damage to mitochondria and mitochondrial dna mtdna leads to aging of humans and animals. The evidence is diverse, deriving from genetics, breeding experiments, and plasticity of life span in stressful environments. Pcd is carried out in a biological process, which usually confers advantage during an organisms lifecycle. In normal aging, a role for the emergence of mutator polg molecules also needs to be considered, and it will be important to determine whether pol. The mitochondrial theory of aging and its relationship to reactive. A midlife crisis for the mitochondrial free radical theory of. Mitochondria in aging, i mechanisms and background josh. The mitochondrial theory of aging mta was first proposed in 1972 by denham harman, the father of the free radical theory of aging frta 1. A number of aging theories have been proposed 1 5, and the mitochondrial free radical theory of aging mfrta has taken center stage for several decades.
The hope was that by quenching the ros, aging might be turned off. Mitochondrial dysfunction has long been considered a major contributor to aging and agerelated diseases. This is related to an evo lutionary theory of aging called the disposable soma theory. Mitochondrial theory of aging and other aging theories theories have developed regarding the key role mitochondria play in the aging process which have sparked new research regarding how mitochondria may be influenced by lifestyle and science to enhance quality longevity and fight disease. Agerelated changes in mitochondria are associated with decline in mitochondrial function. Theory of aging definition of theory of aging by medical.
Since organism functional efficiency for many species e. Landes company ey intracellular antibodies wayne a. The mitochondrial theory of aging represents one of the leading theories on skeletal muscle aging harman, 1972. All of these observations fit well with the longstanding notions of the freeradical theory of aging that postulated a causal role for ros in the aging process harman, 1956. There are compelling reasons to regard aging as an evolved adaptive program. The mitochondrial free radical theory of aging suggests that antioxidant supplements can repair the damage caused by free radicals. The mitochondrial free radical theory of aging mfrta proposes that mitochondrial free radicals, produced as byproducts during normal metabolism, cause oxidative damage. With advanced age, mitochondrial dna volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species ros. Psychosocial theories on aging january 12, 2006 what guides theories. Mitochondrial theory of aging maturesroles of mtdna.
The mitochondrion in aging and disease, volume 127 1st edition. According to this theory, ros are considered to be unwanted toxic byproducts of aerobic metabolism that induce oxidative damage to various cellular macromolecules due to their high. An estimated 300 theories have been put forth over the years to explain why aging occurs. Pdf the mitochondrial free radical theory of aging. Mitochondria are tiny cellular bodies or organelles, and are among the most complex structures within the cell. The basis for the mitochondrial free radical theory of aging mfrta was provided by denham harman 1, 2, who recognized the possibility of a connection between mitochondrial oxidative phosphorylation, oxygen free radical formation, cellular damage and the general degenerative phenotype of aging.
Reconsidering the role of mitochondria in aging the. In fact, many scientists believe that humans have long lifespans because we are much better at repairing our genome than shortlived animals like mice. First proposed in 1972, the mitochondrial theory of aging suggests that its free radical damage to our cells power source, known as mitochondria, that leads to a loss of cellular activity and function over time. Mitochondrial aging and agerelated dysfunction of mitochondria. Mitochondrial function is intricately linked to why and how we age. The term cellular senescence therefore denotes a stable and longterm loss of proliferative capacity, despite continued viabilityyy and metabolic activity. The mitochondrial free radical theory of aging mfrta. Today we are going to harness the power and discuss the mitochondrial decline theory of aging. The gene regulation theory of aging proposes that senescence is the resulting of changes occurring in the gene expression kanungo 1975. Nuclear dna damage can contribute to aging either indirectly by. Although it is clear that many genes show changes in expression with age, it is unlikely that selection could act on genes that promote senescence directly weinert and timiras 2003. But based on the classical neodarwinian understanding of population genetics, there are powerful theoretical reasons to believe that aging could not have evolved as an adaptation.
For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose. Jul 18, 2017 the gene regulation theory of aging proposes that senescence is the resulting of changes occurring in the gene expression kanungo 1975. Unless you have a background in the biological sciences you may have never heard of mitochondria. Mitochondria are organelles in the cells that produce the energy needed to sustain life. According to mfrta, the accumulation of this oxidative damage is the main driving force in the aging process. This is a pdf file of an unedited manuscript that has. Mitochondrial research group, school of neurology, neurobiology and psychiatry and institute for ageing and health, newcastle university, medical school, framlington place, newcastle upon tyne, ne2 4hh, uk. Empirical research, previous literature culturalsocial historical climate theory producers own values and interests also usually the result of a culturalsocial historical climate aging theories 1. The mitochondrion in aging and disease, volume 127 1st. However, this practice is contradicted by a large body of evidence which shows that antioxidant supplements are often harmful. The mitochondrial theory of aging and its relationship to. We collected resting muscle biopsies from the vastus lateralis, and 24 h urine samples from, young n. In order to understand the programmed adaptive aging vs.
1535 1247 1603 1099 1553 140 762 288 408 1077 672 98 772 531 1017 12 821 85 620 1567 938 444 806 1059 600 1067 206 611 458 706 1020 933 1045