Longevity: Future Direction and Conclusion
April Barnado
Future direction of Longevity |
Image used from Microsoft Word Clip Art, Windows XP Professional.
Current Progress in Theories of Aging Research
What research is currently being conducted to better understand the aging theories to determine how we age? Do the aging theories propose any treatments that will extend our life span? This section will provide a summary of current progress in a few of the aging theories.
Telomeres, Telomerase, and Cancer
Disease Studies: Werner's Syndrome and Hutchinson-Gilford Progeria
Telomeres, Telomerase, and Cancer
Studies with Mice
As we age, cells with dysfunctional and shortened telomeres accumulate resulting in increasing senescent cells. As noted above, this accumulation of senescent cells can lead to a group of dysfunctional, mutant cells that can give rise to tumor formation. Studies in mice have been done to investigate the relationship between shortened telomeres and the occurrence of tumor formation and cancer. However, unlike humans, telomere shortening and resulting cell senescence is not normally seen in mice. Thus, scientists have genetically engineered mice that have inactivated telomerase and thus do not express telomerase in their cells. As a result, the mice telomeres shorten after each cell division, similar to humans. In these mice, scientists have observed that after four to five generations of cell division, the telomeres in mice are shortened to an extent that model the shortened telomeres observed in humans, particularly in senescent cells from aged human donors. These mice with the shortened telomeres develop cancer, particularly epithelial cancers and other pathologies common in human aging (Kim et al., 2002).
These studies show that shortened telomeres that result in cell senescence could be a factor in aging and particularly in developing age-related pathologies such as cancer. However, these studies involve the mouse model, which as explained above does not closely match the human model. Recall that progressive telomere shortening and the resulting cell senescence is not observed in normal mice. The mice have to be modified by inactivating telomerase in order to serve as a comparable model to humans. However, the mouse model is currently one of the few models available to investigate the relationship of telomere length to aging and cancer. In using this model, scientists are continually trying to improve the conditions of the experiments to ensure that the mouse model of telomeres will match as closely as possible to the human model.
STELA
The telomere theory assumes that the shortening of telomeres and the subsequent increase in senescent cells is responsible for aging. Thus, from this theory, one could infer that with longer telomeres, there would be increased longevity. Longer telomeres would not shorten as quickly, and thus cells would not become senescent as prematurely. Tissues would also not degrade as quickly. However, do longer telomeres actually result in long er life spans? Until now, scientists are just beginning to be able to measure telomere length in human cells efficiently.
In 2003, scientists at the University of Wales in the United Kingdom developed a technique to measure telomere length in human somatic cells. This new technique is called STELA and can measure telomere length in a single cell from any tissue sample.
For more information on the discovery of this technique, please see the following link to a BBC Health News article from 2003: http://news.bbc.co.uk/1/hi/health/2676735.stm.
The scientists have used STELA to show a relationship between telomere length in parents and their children. This relationship that children and parents both share similar telomere lengths suggests that genetics plays a significant role in telomere length and possibly longevity. Dr. Baird of the University of Wales commented that “Essentially STELA will allow us to find out whether telomere erosion has anything to do with aging in humans” (BBC Health News, 2003). This research will help scientists determine whether there is a link between longevity and telomere length.
Telomerase
As noted in the above section, most of our somatic (body) cells do not express telomerase to help maintain telomere stability and length. However, could treatments make cells express this enzyme? Could cells then overcome the limit of cells divisions that it undergoes before entering cell senescence? Current research in adding telomerase to human cells is fairly limited due to the risk that the addition of telomerase could result in “immortal” cells that could cause tumor development. Scientists would have to engineer a precise delivery system adding the exact amount of telomerase needed to elongate the shortened telomeres but not create “immortal” tumor cells that could result in cancer. Please see Dermal Studies and Complications in the next section for more details.
Summary on Progress for Telomere Theory Research
Telomere dysfunction and instability is caused by “replication-mediated shortening, direct damage, or defective telomere-associated proteins” resulting in “three cellular outcomes: senescence, death, or genomic instability” (Kim et al., 2002). Cell senescence and particularly genomic instability can lead to tumor formation and eventually the development of cancer. Therefore, telomere dysfunction may contribute to aging because it induces cell senescence as well as contribute to diseases involving degradation of tissues that are common in aging, such as cardiovascular disease and Alzheimer’s dementia. However, the causal link between cell senescence, telomere length, and aging has still not been clearly established by the scientific community.
Cell Senescence
The cell senescence theory explains that cell senescence “underlies” aging but does not cause aging (Fossel, 2000). Until very recently, studies have not been able to test how cell senescence affects human aging due to lack of technology. However, now there is actual in vivo (in the body) testing in humans to explore the theory of cell senescence. The goals of this research is to find clinical interventions of preventing and possibly even resetting the “cellular clock” or the cell’s limited number of divisions before undergoing cell senescence.
Current studies have been done and are being pursued that investigate transplanting normal healthy cells into aging tissues and cell areas, particularly the dermis of the skin and the immune system.
Dermal Studies
In 2000, studies were done that transplanted young human fibroblasts and keratinocytes into mice in order to observe if there was growth of normal skin. The scientists observed tissue that was physically and genetically identical to normal “young skin” (Shelton, et al., 1999, as cited in Fossel, 2000). If the scientists used senescent human cells in the transplant, the skin in the mice looked typical of “old” human skin. However, if the senescent cells were transfected with human telomerase and certain growth factors, the new tissue was typical of “young” human skin. The addition of the human telomerase helped lengthen the dangerously short telomeres that threaten the cell’s stability (Funk, 1999, as cited in Fossel, 2000). The added human telomerase seemed to alter the gene expression in the cell to help it overcome cell senescence, in a pathway or process that scientists currently do not understand (Fossel, 2000). This study seems to suggest that dermal aging is closely connected with cell senescence and that the process of dermal aging is reversible. Thus, it is possible that the addition of human telomerase to aging dermal cells could be a potential “treatment” to aging skin. However, there are complications and more research to be done in animal models before in vivo (in the body) testing can be done in humans.
Immune System Studies
The immune system is another system studied in efforts to develop a treatment that will “reverse” cell senescence in damaged and aging tissues. Specifically, studies have been done ex vivo (outside the body) with adding human telomerase to human leukocyctic stem cells (Effros, 1998, as cited in Fossel, 2000). By adding this human telomerase, studies have shown that cell senescence can be “reset” and cell growth can continue. Since the immune system is a system with easy transfection of agents such as human telomerase, the immune system will likely be used in future follow up studies, possibly with in vivo studies in humans.
Complications and Summary
Even though this theory sounds promising, with effects of adding human telomerase, there is always the risk that the telomerase will help the tissue of interest grow out of control resulting in tumors and possibly cancer. Thus, there is a huge risk in doing experiments, which involved transfecting human telomerase in human studies. Scientists and ethicists are asking whether the risks to perform such experiments would outweigh the benefits of enhanced immune function, treatment for aging skin, and increased knowledge in the link between cell senescence and aging. Also, the studies and experiments explained above are limited to the dermis of the skin and the immune system. It would be hard to find elderly volunteers that would allow transfection of human telomerase and growth factors into damaged cells of the heart, arteries, and supporting cells that help neurons function in the brain. However, precisely such studies in these tissues would be necessary to develop treatment options for some of the major diseases associated with aging, namely atherosclerosis, other cardiovascular diseases, and Alzheimer’s dementia.
Current research is also investigating certain disease studies in efforts to study how we age. Specifically, scientists are focusing on two rare genetic diseases called Werner’s Syndrome and Hutchinson-Gilford Syndrome. Both of these rare genetic disorders are progerias. Progeria is a general term to describe diseases involving premature aging. With this premature aging comes the premature degradation of the body’s tissues.
These rare human genetic diseases resemble accelerated aging and thus serve as useful models for scientists investigating the aging process. These models are particularly useful because they are human models and thus avoid the problems of different model organisms such as mice having different aging processes and cellular mechanisms. Any observations or information gained from using these disease studies would be directly relevant to humans.
Progeria disease studies particularly focus on the known single-gene mutations in these diseases and what role these mutated genes play in the cell’s functioning. Further, these genetic diseases, particularly Werner’s Syndrome, supports the theory that cell senescence is associated and even may cause normal aging (Kipling et al., 2004). However, it is important to note that the aging process in these two progerias is similar but also very different from normal aging. Thus, knowledge gained from research in this area may not directly apply to understand normal human aging.
Werner’s Syndrome
Werner’s Syndrome is a rare genetic disease that affects approximately about 3 in 1,000,000 persons while approximately 1 in 200 persons are carriers for the disease. Symptoms normally start in the early to mid 20’s, and death is usually expected in the mid 40s. The major cause of death is a heart attack or other heart-related complications and/or diseases. (Karen Bernd, 2002)
List of Symptoms (International Registry of Werner’s Syndrome, 2004 and Martin and Oshima, 2000)
Note that these symptoms are typical conditions seen in aging as tissues wear down.
Please see the following link to see the “accelerated aging” that a typical Werner’s Syndrome patient would undergo: http://www.pathology.washington.edu/research/werner/
Relation to Aging
It is important to note that while Werner’s Syndrome appears to “mimic” the aging process, there are some aspects of the disorder that are very different from the normal aging process (Kipling et al., 2004). Thus, scientists are challenged to determine which aspects of Werner’s Syndrome are identical or at least similar to the normal aging process. Currently, scientists are finding that the effects of the mutation and the premature increase of senescent cells are the aspects of Werner’s Syndrome that seem to mimic most closely the normal aging process.
Mutations and the Three R’s
The clinical symptoms of Werner’s Syndrome not only appear in an accelerated aging process but also the symptoms advance much more quickly and are more severe than those seen in the normal aging process. It is believed that Werner’s Syndrome is caused by a variety of mutations that affect a certain family of DNA helicases. The DNA helicases lose their function and cannot assist in DNA replication to help unwind the DNA at the replication forks. The replication forks are stalled, and DNA replication cannot continue. Thus, damaged, senescent cells or cells on the pathway to undergo programmed cell death or apoptosis cannot be replenished as readily, resulting in a decline of active, dividing cells.
Cell Senescence
Scientists further theorize that the key causes of the symptoms observed in Werner’s Syndrome are due to the mutation in the DNA helicase that renders it functionless in DNA replication. Scientists can link Werner’s Syndrome to aging by concluding that aging can result from mutations affecting key cellular processes such as DNA transcription, translation, and replication. Thus, as we age and have a higher probability of accumulating mutations and genomic instability, cellular processes can be severely affected and rendered inefficient. The accumulation of mutations and genomic instability can result in more and more senescent cells and a decline in active, dividing cells.
Mice studies have been conducted using mice that are deficient in the gene that encodes for the DNA helicases. (This deficient gene in the mice models is the same gene that is mutated in Werner’s Syndrome patients that renders the DNA helicases nonfunctional.) In these studies, analyses were conducted to determine if the mice underwent any obvious premature aging. The scientists found that despite the fact that most of the cellular processes affected in Werner’s Syndrome patients were “recapitulated” in the mice, the mice showed none of the signs of premature aging (Lebel and Leder, 1998, as cited in Kipling et al., 2004). This observation suggested that genomic instability or having a mutation affecting a major cellular process, such as the mutated helicase affecting DNA replication, is “in itself, not sufficient to produce premature aging in mice” (Kipling et al., 2004). Further, these observations implicate that accumulation of mutations that affect major cellular processes is not the sole cause of aging. Instead, cell senescence, observed in Werner’s Syndrome and normal human aging, may be a very important player in causing aging.
Summary of Werner’s Syndrome and Aging
Scientists have concluded that Werner’s Syndrome studies have shown that cell senescence may play a causal role in normal human aging (Kipling et al., 2004). However, there is no definite estimate of how many senescent cells must accumulate before the physiological signs of aging are seen in tissues or before the common symptoms of aging are manifested. Studies with Werner’s Syndrome have implicated that the symptoms of premature aging, particularly the wearing down of the skin, appear when cells of the dermal layer of the skin are reduced to only twenty populations of cells dividing or doubling (Kipling et al., 2004). However, scientists are waiting on more data from other progeria models in order to better understand how many senescent cells are needed for humans to start showing signs of aging.
Hutchinson-Gilford Progeria
Hutchinson-Gilford Progeria (HGP) refers to a very rare genetic disorder that is sometimes referred to as “progeria of childhood” or “progeria.” This genetic disease affects approximately one in one million people. Children afflicted with this disease usually die by the age of thirteen due to various types of cancers and/or cardiovascular problems. Many of the symptoms in this syndrome are similar to the ones observed in Werner’s Syndrome. However, interestingly, many of the symptoms common in “normal” aging are not seen in Hutchinson-Guilford such as cognitive decline, brain lesions from Alzheimer’s Disease, cataracts, or age-related visual and hearing impairments.
List of Symptoms
Relation to Aging
Hutchinson-Gilford Progeria (HGP) is a genetic disorder whose causes were unknown. However, recently, studies in 2004 have shown that the genetic disorder is caused by a dominant mutation in lamin A/C (Goldman et al., 2004, as cited in Kipling et al., 2004). Cells from HGP patients show disruptions in the nuclear lamin that worsen with ongoing cell division or as the organism ages (Kipling et al., 2004). Nuclear lamin is a meshwork of protein filaments under the inner membrane of the nucleus. Scientists do not completely understand how the defected lamin affects cellular function. However, they hypothesize that cellular processes such as transcription and DNA replication require intact lamin in order to function properly. Further, scientists have found that cultures of cells from HGP patients show elevated rates of apoptosis or programmed cell death as well as accelerated cell senescence. Thus, with accelerated cell senescence, there are fewer cells that are actively dividing to replace the senescent or damaged cells resulting in degraded tissues and premature aging.
HGP provides an informative model on human aging. However, less is understood about this disorder in comparison to Werner’s Syndrome. Scientists hope to create mice that have genetic defects similar to the ones observed in HGP patients in order to investigate the role of accelerated rate of cell senescence on premature aging and to further better understand HGP.
This theory assumes that we age because of the accumulation of oxidative stress and damage to our cells. Thus, we should be able to extend average life span by simply reducing free radicals and oxidative stress. However, this statement is based on the assumption that oxidative stress has a significant role in the aging processes and that resisting oxidative stress determines longevity. This statement is based on a hypothesis and theory, and scientists are far from establishing a causational relationship between free radicals, oxidative stress, and aging. However, this theory has implicated interests in testing and pursuing various treatments and therapies.
Current research has been exploring ways of reducing oxidative stress by investigating whether diet and caloric restriction may reduce oxidative stress and by investigating genes that appear to make the organism resistant to oxidative stress.
Diet and Caloric Restriction
Simply limiting food intake or restricting one’s calories has long been shown in animal models as a way of reducing free radicals and oxidative stress. There is less food to break down; thus, fewer free radicals are generated in the metabolic processes of the cell. However, pursuing this caloric restriction in humans could raise ethical concerns and practical difficulties that would prevent its effectiveness as a therapy. There is also the possibility of dietary supplements that could enhance our antioxidant defenses. However, studies in mammalian models have shown that dietary supplements have had little or no effect in enhancing longevity (McCall, et al., 1999 and Yu, 1999, as cited in Finkel and Holbrook, 2000). More studies need to be conducted on these dietary supplements to determine dosage and the exact mechanism of how they work or do not work. Currently, aging research is looking to the rhesus money as a new model for investigating the links between diet and caloric restriction to aging. The rhesus monkey shares 92.5 to 95% of DNA human, and thus there would be many biological similarities with humans with the genetics of aging (Roth, et al., 2004).
There is also the problem that simply adding a dietary supplement or drug will not affect the cell’s complex balance of maintaining some free radicals that are normal for the cell. Further, scientists agree that aging is a multifactorial process and solely focusing on therapies reducing free radicals and oxidative stress will unlikely directly affect how long we live and how we age.
Disclaimer on Antioxidants in the Diet
Little or no evidence exists that show dietary supplements that include “so called” antioxidants actually help to reduce free radicals and oxidative damage when ingested. However, the sales of dietary supplements and antioxidants continue to soar. Even some physicians and scientists are claiming that taking antioxidants are way to increase longevity. Dr. Wikenheiser, a Canadian scientist with ten years of aging research experience highly recommends taking antioxidants as a way to “neutralize” the damage done to the body by free radicals and oxidative stress (BBC Health News, “Taking control of the ageing process,” 2002). However, this theory that antioxidants from diet or dietary supplements “neutralizes” the negative effects of oxidative stress and free radicals has not been clearly shown in scientific studies.
Further, Dr. Wikenheiser has invented a questionnaire that calculates a person’s true biological age. Then, Dr. Wikenheiser has a list of recommendations to help a person lower his or her biological age up to ten years in three months with lifestyle changes including diet, exercise, and stress management.
For more information on Dr. Wikenheiser, please see the following BBC Health News article from 2002: http://news.bbc.co.uk/1/hi/health/1773326.stm.
Image used from Microsoft Word Clip Art, Windows XP Professional.
Genes Resistant to Oxidative Stress
Responses to "longevity genes"
Genes Resistant to Oxidative Stress
Scientists have recently discovered that certain genes in model organisms may play an active role in increasing oxidative stress resistance and longevity. Conversely, mutations in these genes can decrease oxidative stress resistance and longevity. In C. elegans, a eukaryotic (unicellular or multicellular organism that contains a membrane-bound nucleus) worm, scientists have established genetic links between oxidative stress responsiveness and longevity. If these organisms have certain genes that are known to increase responsiveness and resistance to oxidative stress, these organisms have a 25% to 100% increase in longevity, depending on the gene. Similar findings for fruit flies (Drosophila melanogaster ) and mice show a 35% and 30% increase in longevity, respectively (Finkel and Holbrook, 2000).
Geneticists and aging researchers are currently searching for “longevity genes” in humans that may play a role in our resistance to oxidative stress.
“Longevity genes” in model organisms
SIRT1 This gene was first discovered in Saccharomyces cerevisae (brewer’s yeast) and then mice and human models in 2004. It is proposed that this gene extends life span by preventing cell senescence and death from oxidative stress. However, the mechanism of preventing oxidative stress and cell senescence is not known (McDonald, 2004).
For more information, please see the following link: http://www.bio.davidson.edu/courses/genomics/2004/McDonald/longevity_gene.htm.
Indy (stands for “I’m not dead yet”) This gene was first discovered in 2001. A mutation in this gene in fruit flies (Drosophila melanogaster ) restricts the cells’ energy absorption or effectively “puts the cell on a diet” (BBC Health News, 2000). Further, a mutation in this gene results in the fruit flies living about twice their normal life span and also maintaining a higher quality of life even at an extended life span.
Methuselah This gene was first discovered in 2001 along with Indy. A mutation in this gene in fruit flies (Drosophila melanogaster ) expands life in fruit flies by approximately 35%. Unlike Indy, scientists do not know how this gene works to extend life span (BBC Health News, 2000).
Shc This gene is found in mice and when mutated can cause a 30% increase in life span. It is proposed to enhance oxidative stress resistance to UV radiation and formation of free radicals (Finkel and Holbrook, 2000).
Current searches for “longevity genes” and other genetic links to longevity
Scientists have also been searching for genes and other genetic links to longevity in higher animal models and in humans. Unlike the genes listed above that affect how the organism’s cells resist oxidative stress, these genes are suggested to affect longevity through other mechanisms. These genes appear to help the cell mend DNA and cellular damage and then proceed with normal growth. Below is just a brief list of a few of the “longevity genes.”
FOXM1B This gene was discovered in 2002 that is thought to help the body’s tissues heal and replenish themselves by replicating the cells of the tissue. Specifically, researchers at the University of Illinois at Chicago have shown that if there is a mutation in the FoxM1B gene that the ability for the body to replicate its cells is impaired (BBC Health News, “Ageing process ‘key’ pinpointed,” 2002).
Further, the researchers concluded that mutations in this gene and others are more likely to accumulate as we age (BBC Health News, “Ageing process ‘key’ pinpointed,” 2002). These findings seem to provide a link between the accumulation of mutations and aging. Also, researchers uncovered a link between the cell cycle and aging. Mice with liver cells lacking the FoxM1B gene were unable to regenerate their damaged liver cells quickly and effectively. Scientists uncovered that the regeneration was slow because in the liver cells without the FOXM1B gene the cells often failed to undergo the S (Synthesis) phase of the cell cycle. Without undergoing the S (Synthesis) phase, the cells had problems dividing or completing the cell cycle, resulting in slow regeneration of cells.
For more information on this gene, please see the following link: http://news.bbc.co.uk/1/hi/health/2614431.stm.
PARP-1 PARP-1 is not a gene but a protein that was discovered in 2001 and is thought to mend damaged strands of DNA in animal models (BBC Health News, 2001). Researchers at Newcastle University in the United Kingdom have observed that animals with different lifespans have different versions of PARP-1 (BBC Health News, 2001). Specifically, they have observed that mice with a short lifespan have a less effective form of the protein compared to other mice and animals that live longer. Further, the researchers have hypothesized that maybe the differences in longevity in humans could be explained partly by some having a deficiency of PARP-1 or having a less effective form of the protein. The researchers are currently exploring this hypothesis by investigating the PARP-1 generated in mice and other animal models as well as engineering cells with different versions of PARP-1 and observing whether DNA suffers or resists damage under oxidative stress. They claim that they have engineered cells in animal models which are able to resist DNA damage when placed under oxidative stress (BBC Health News, 2001).
For more information on this protein, please see the following link: http://news.bbc.co.uk/1/hi/health/1305112.stm.
For more information on other current research on “longevity genes,” please see the following link to the Aging Research Center (ARC) and scroll down to “Recent Aging Related Articles:” http://www.arclab.org/.
Responses to “the longevity genes”
Currently, the media portrays that aging is strongly controlled by “the longevity gene.” They further claim that if scientists could only find that one “longevity gene” that genetic therapies could be developed to alter the gene to extend lifespan. If one was not born with a good copy of the “longevity gene,” then scientists could give you a good copy of the “longevity gene” through genetic therapy or some form of genetic engineering.
Unfortunately, very little gene therapy research has been done in longevity research. A few studies have been done with engineering cells in mice and in animal models as explained above with PARP-1. However, this area of genetic engineering is far from allowing scientists to attempt genetic engineering and therapy in “longevity genes” to enhance longevity. Scientists are just beginning to find and understand the mechanism of “longevity genes” in humans.
Even though “longevity genes” have been found, finding these genes does not implicate that scientists have finally discovered the answer to how we age. First, the mechanisms of how these genes affect longevity, i.e. reducing oxidative stress or helping the cell to repair itself and its DNA, are all based on theories that try to explain how we age. Even if one of these theories were strongly supported by evidence, aging is known to be a multifactorial process. Thus, one of the theories would only describe one aspect of how we age. Second, by solely focusing on the progress of finding “longevity genes,” science would be neglecting the importance of environmental effects on how we age. Leonard Hayflick, one of the leaders in the field of aging research emphatically states that
“Ageing is not a programmed process governed directly by genes” (Hayflick, 2000).
Genetic versus Environmental Influences on Longevity
In focusing on how both the environment and genetics influence how long we live, it is important to examine quantitative genetics studies and statistics. Quantitative genetics refers to the study of quantitative traits or complex, multifactorial traits that vary across the population and are associated with multiple genes (Hales, 2004). Longevity is believed to be such a trait as well as traits such as personality, intelligence, and various alcohol and drug addictions. In quantitative genetic studies, scientists try to determine how significant is the genetic versus the environmental influence on the trait of interest. Subjects for these studies mainly include identical twins since they share the same DNA. Thus, if identical twins share the same trait at a high rate or percentage, there could be a strong genetic influence on that trait. Note that other subjects are used in these studies such as fraternal twins, siblings, first cousins, etc.
Quantitative Genetic Studies on Longevity
Various quantitative genetic studies have been conducted using longevity as a trait. Specifically, one such Scandinavian study used identical and fraternal twins to calculate the heritability of life expectancy (McGue et al., 1993, as cited in Perls, et al., 2002). Heritability is a percentage that estimates the genetic influence on a trait. The scientists adjusted for environmental factors for both the identical and fraternal twins and concluded that the environmental factor played a minor rule in determining the final heritability calculation. It is important to control for the environmental factor because not only do identical and fraternal twins share the same or nearly the same DNA but also often share the same environment. From this study, the heritability of life span was calculated to be between twenty and thirty percent (McGue et al., 1993, as cited in Perls, et al., 2002).
Scientists have interpreted this result to indicate that seventy to eighty percent of how long a person lives is determined by environmental factors such as the individual’s behavior, eating and exercising habits. This result conveys an empowering message because it arguably allows an individual some “control” over how long he or she can live. However, this study examined twins that had an average life expectancy similar to the one observed in the general population. Thus, this study did not account for genetic and environmental influences on “extreme longevity,” living to ages of a hundred years and beyond. In order to investigate environmental and genetic influences on “extreme longevity,” centenarian subjects would have to be studied.
Statistics about Centenarians
Studies have shown that among industrialized countries, the number of centenarians is increasing at a rate of about 8% per year (Perls, et al., 2002). For example, in the United States at the turn of the twentieth century, there were approximately one centenarian per 100,000, and now there is about one per 10,000 (Perls, et al., 2002). Studies project that there will be at least 800,000 centenarians among the baby boomer generation (Perls, et al., 2002). This increase in centenarians is due mainly to medical advances. However, interestingly, the number of centenarians that are reaching the ages of 120 years and beyond is not increasing. In fact, people that attain these ages do not exist except Jeanne Calment of France who lived to be 122 years old. Therefore, it seems that science and medical advances cannot help an individual live many years beyond the average expected life span of about eighty years.
Centenarian Studies
In 2002, a centenarian study was conducted using over two thousand siblings of centenarians and examining over four hundred pedigrees or family trees of centenarians. Specifically, the age of survival for siblings of centenarians was compared to the age of survival for a person in the general population. Researchers found that the age of survival for siblings of centenarians was significantly different from the average age of survival for a person in the general population (Perls, Kunkel and Puca, 2002). This data seems to indicate that there is a very strong familial component (both genetic and environmental factors) to “extreme longevity” since siblings do share similar genes that could result in extreme longevity but also share the same home environment and possibly similar eating and exercise habits that could also result in “extreme longevity.” However, researchers have concluded that even with considering the environmental factor that there is a “significant genetic component” to “extreme longevity” (Perls, Kunkel and Puca, 2002).
Image used from Microsoft Word Clip Art, Windows XP Professional.
The centenarian study and other quantitative genetic studies show that not only our genes but also the interaction of our genes with our environment affects how we age. Thus, in addition to our genes, our diet, exercise habits, and stress levels all may affect how we age. However, simply changing the environment, i.e. taking a dietary supplement or antioxidants, will not cause a person to increase how long he or she will live.
In recognizing the strong but not absolute genetic influences on longevity, science must pursue aging research to understand how we age and to determine what genes are implicated for controlling and regulating the aging process. As explained earlier, “longevity genes” in animal models have been discovered that control and regulate the aging process. However, more research is being done and is needed to find similar homolog “longevity genes” in humans and also to better understand the mechanism of the “longevity genes” in the animal models. It is also important for scientists to focus on the theories of aging explained earlier with telomeres and cell senescence. Particularly, the area of cell senescence is very promising because scientific studies have shown powerful causal relationships between increased cell senescence and premature symptoms of aging in animal models. More knowledge about cell senescence is needed before similar research can be pursued in human models.
In recognizing the environmental influences on longevity, research is continually being pursued to better understand the free radical theory. The free radical theory suggests that environmental factors of diet, exercise, and caloric restrictions can affect the oxidative stress in our cells and may affect longevity. While there has not been much success in showing that taking dietary supplements with antioxidants affects life span, research in animal models shows that a restricted diet and caloric intake can clearly increase life span.
Ethical Considerations: Quality versus Quantity of Life
Current research shows that science is not yet equipped to increase human life spans. However, science has progressed and continues to progress in understanding how we age. With the theories of aging, especially with cell senescence, there is a conflict that science creates of whether there is a finite limit on how long a person can live. Further, can or should science ever push that limit?
With this question, another important conflict arises of how to balance quantity versus quality of life. Would it be better to live the maximum human life span of around 120 years with a few major health problems or live 100 years free of debilitating diseases? Considering these two views of quantity versus quality of life, should aging research focus more on understanding how to defeat cell senescence and the effects of oxidative damage on the cell in order to increase life span? Or should aging research instead focus on understanding and treating the debilitating diseases that accompany aging?
Please see the following link to the Ethics section of the Genetics page for a more thorough overview of the ethics related to Longevity and other genetic issues:
Questions or Comments: Email Dr. Verna Case
Davidson College Biology Department
Davidson College
This web page was produced as an assignment for an undergraduate course at Davidson College.
Future direction of Longevity |