Aging Is Not a Genetic Dustbin

Nature designed us to age for a reason.

Harmful genes that cause Huntington’s disease — a disease that attacks the neurons in the brain — only show up between ages 30 to 50, in some cases after the birth of offspring. There are many other diseases that accumulate later on in life, dementia being the main one. In 1952, Peter Brian Medawar tried to explain this by suggestion that older adults accumulate mutations and become a "genetic dustbin."

In Medawar's theory, there is no advantage to aging, nor are there any benefits for older people to live. Aging is simply the result of declining functions before death. This biological interpretation proved popular.

To explain aging, biologist George Williams in 1957 came up with the "antagonistic pleiotropy hypothesis" (named by Michael Rose in 1982). Pleiotropy is the phenomenon where one or a few genes control more than one trait. The antagonism part comes from the negative effect that emerges later on in life. As an example, testosterone in men might result in an attractive, muscular body in youth, as well as masculine features, such a deep voice and facial hair, but it also increases the likelihood of prostate cancer in older age, hence the antagonistic part of the pleiotropy. Although it is the positive aspects of the pleiotropic gene that are selected for in natural selection, the antagonistic aspect also sneaks into the gene pool. Aging is seen as an invisible cloak that sneaks bad genes into the gene pool by cloaking them under positive traits when young. Aging, in this view, has subverted the whole process of natural selection by disguising itself as a positive attribute in early life and then transforming — in a Jekyll-and-Hyde metamorphosis — into an aging liability. Somehow nature has been hoodwinked into allowing people to get old. Aging becomes a problem, a genetic dustbin of humanity. From here, it is fairly easy to see the approach: We need to cure aging, because nature made a mistake. The hubris of judging that nature made a mistake ignores that nature might have a different perspective from ours.

As a species, survival is nature's only ambition.

The only way that successive generations prosper is if they are a good fit with their environment. Each generation must survive long enough to create another generation. Nature keeps our genes immortal, and it has two extreme methods to achieve this single aim. One way is to produce an enormous number of offspring and hope that a few survive to then pass on their genes (known as r-selection). Another approach — one followed by humans — involves having few children whom we nurture until adulthood and beyond (known as K-selection). Therefore nurturing — protecting and supporting others — is our survival strategy, not competition.

Nurturing involves having things to teach and living long enough to be able to teach them. Which is why humans live long and have such a big brain; the two go together. Some 1.6 to 1.9 million years ago, our brain grew very fast; some say — not without contention — that brain expansion mirrors the development of cooking. Cooking, making food more easily digestible, resulted in greater availability of nutrients for the hungriest organ in our body — our brain. Nature engineered us to have both a big brain and longevity; they are intricately intertwined. We can see this through mathematical models that show a leap in predictive value when older people are included in the equation. Whether or not older people have a disease, the presence of older people in the family predicts longer-living children and grandchildren.

In the wild, most mammals die once they lose their ability to reproduce. Humans are different. We continue to live well past our capacity to reproduce, especially females. Is nature wrong again, or does nature have a special role for older people?

What the genetic dustbin proponents do not appreciate is that older people, especially grandmothers, have a statistically positive effect on their community. In 2004 while examining the “grandmother effect,” Mirkka Lahdenperä of the University of Turku, Finland, and her colleagues found statistical evidence that a grandmother has a decidedly beneficial effect on the reproductive success of her children and the survival of her grandchildren. Older adult humans promote the survival of the species. Unlike any other animal, we also transfer wealth, capital, and wisdom to our successive generations way past our reproductive period. When gene survival includes the broader community, then older people have a positive effect on their chances of survival.

By 1973, John Maynard Smith and George Price introduced game theory to evolutionary problems. While classic game theory sees players making rational choices on the basis of individual gain, evolutionary game theory posits an awareness of what others might do and the development of strategies to counter that decision. It is a social decision mode, not a purely individualist one. Maynard Smith argued that since everyone dies, evolution does not benefit individuals. Evolution is designed to benefit the community. In this interpretation, it explains that the strategy humans employ is based on benefits to the community, rather than benefits solely to the individual. Such a model fits the outcomes we see in reality. This insight was revolutionary and transformed the argument from one where aging is seen as a genetic dustbin to one where aging becomes part of a package for survival — a package that includes older adults contributing, in as yet unknown ways, to the promotion of our species.

There are instances where antagonistic pleiotropy of dementia has some really beneficial effects. For example, the Apolipoprotein E Variant 4 that is strongly associated with Alzheimer's disease might have beneficial aspects, such as reducing the rate of age-related macular degeneration, lower testosterone, and although there is no evidence of apoE isoform reducing infectious diseases, there is evidence that apoE could play a role in reducing our susceptibility to viruses, bacteria, and protozoan parasites. Such polymorphisms — having multiple expressions — are abundant in nature.

Despite this insight, in 2002, 51 renowned scientists — including such luminaries as Jay Olshansky, Leonard Hayflick, and Bruce  Carnes — published a position statement in Scientific American stating that “aging is a product of evolutionary neglect, not evolutionary intent.” Again, we are telling nature that it made a mistake, or at least was ignorant of the consequences. When Albert Einstein first confronted quantum physics, he said that “God does not play dice with the cosmos.” What is not reported frequently is the response from Danish physicist Niels Bohr: “Einstein, don't tell God what to do.” It seems that we are telling nature what it should do or how neglectful it is, rather than appreciating the biological system we call life as complete and perfect. We might guess at the intent of evolution — survival of our immortal genes — but we might not understand its methods.

Aging and having a big brain go hand-in-hand. It is nature’s plan for our survival. Older adults improve the survival of both their children and grandchildren. Looking at aging in a broader context allows us to view some of the wonders of nature. We have a lot to learn if we listen.

© USA Copyrighted 2018 Mario D. Garrett

References

Browning PJ, Roberts DD, Zabrenetzky V, Bryant J, Kaplan M, et al. (1994). Apolipoprotein E (apoE), a novel heparin-binding protein inhibits the development of Kaposi's sarcoma-like lesions in BALB/c nu/nu mice. J. Exp. Med. 180:1949–54

Bojanowski, C. M., Shen, D., Chew, E. Y., Ning, B., Csaky, K. G., Green, W. R., ... & Tuo, J. (2006). An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation. Environmental and molecular mutagenesis, 47(8), 594-602.

Hogervorst, E., Lehmann, D. J., Warden, D. R., McBroom, J., & Smith, A. D. (2002). Apolipoprotein E ε4 and testosterone interact in the risk of Alzheimer's disease in men. International journal of geriatric psychiatry, 17(10), 938-940.

Lahdenperä, M., Lummaa, V., Helle, S., Tremblay, M., & Russell, A. F. (2004). Fitness benefits of prolonged post-reproductive lifespan in women. Nature, 428(6979), 178.

Mahley, R. W., & Rall Jr, S. C. (2000). Apolipoprotein E: far more than a lipid transport protein. Annual review of genomics and human genetics, 1(1), 507-537.

Olshansky, S. J., Hayflick, L., & Carnes, B. A. (2002). Position statement on human aging. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 57(8), B292-B297.

Pianka, E. R. (1970). On r-and K-selection. The American Naturalist, 104(940), 592-597.

Roselaar SE, Daugherty A. 1998. Apolipoprotein E-deficient mice have impaired innate immune responses to Listeria monocytogenes in vivo. J. Lipid Res. 39:1740–43

Smith, J. M., & Price, G. R. (1973). The logic of animal conflict. Nature, 246(5427), 15.

Williams, G. C. (1957). Pleiotropy, natural selection, and the evolution of senescence. evolution, 11(4), 398-411.

Jumping Genes and Longevity

We can see how genetics play a role in how long we live. Looking at different species and how long or short they live. But we do not know exactly how this works.

Alexander Graham Bell, the inventor of the telephone, was more passionate about aging. In 1900s he found that people that lived long had long-lived children. Whether this is due to genetics or to providing support to children, or both, remains undefined. But the connection is there. Sometimes despite having the best genes, bad luck just strikes. Take the example of Jeanne Louise Calment, who died at the age of 122 years in 1976. Despite having the best genes for longevity her family did not enjoy these positive attributes. Sometimes bad luck negates good genes when her daughter Yvonne, died at age 36 of pneumonia. Luckily, she left a son Frederic, who became a physician. He lived with his grandmother in her apartment. However, he also died early,  in a motorbike accident, at the same age as his mum 36 years old. Sometimes bad luck negates any genetic advantages.

Three classic experiments define how a genetic advantage results in living longer. The first experiment was conducted by Michael Rose who by allowing only eggs of older flies to hatch he found that the next generation lived longer. The new generation seemed to know that, similar to their parents, they need to live longer in order to reproduce. We also find this among humans. The older your mother was when she conceived you, the longer you will likely live. Unlike human, there is no nurturing for flies, so this effect is predominantly genetic.

The second type of experiment uses a naturally occurring disorder in a flatworm that produces less growth hormone which stunts their growth but they end up living much longer. Through a series of trial and errors Cynthia Kenyon at University California San Francisco managed to chemically knock out one of these genes in normal flatworms and in so doing nearly doubling their lifespan.

The third type of genetic observation is seen with mice, in particular the work done by Richard Miller and his infamous dwarf mouse called Yoda. Again, nature lead the way in showing us about the longevity advantage of having less growth hormones. In nature there are three types of dwarf mice that share this longevity characteristic: Snell, Ames and Laron dwarf mice. These mice live about three times longer than average.

By knocking out a gene to stop growing larger we could all live longer. Somehow the body knows that we need to live longer in order to be able to pass on its genes. Fortunately, we also have examples among humans as well. In a southern Ecuador community of 250 individuals that have Laron syndrome—causing a deficiency in primary growth hormone—although protecting them against disease, especially cancer, this apparent protection does not translate to living longer. This group unfortunately engage in risk behaviors in particular alcoholism that negate this genetic advantage.

No one wants to have a stunted growth in order to live longer. But what about having older parents to increased longevity? In biology, there is always a dark side—known scientifically as antagonistic pleiotropy.  This construct has plagued gerontological research since it posits when one gene controls for more than one trait (e.g. height) it is likely that one of these traits is beneficial (e.g. more athletic) while another side is detrimental (e.g. heart disease) to the individual later on in life.

The dark side is that we know that women having children at much older ages increases the risk of certain genetic problems. It has also been reported in 2018 by Boris Rebolledo-Jaramillo with Nottingham-Trent University UK, and his colleagues that children of older mothers face greater risk of developing diabetes, dementia and heart disease. As for older fathers, their kids are more likely to have dwarfism or Apert syndrome.  Newer research in 2012 by Augustine Kong at Reykjavik University, Iceland also suggest that there is an increased risk for autism and schizophrenia. There is a “goldilocks effect”, not too old and not too young, just right.

The surprising result in genetic research is the finding that as we age we are also changing our genes. It was always assumed that our genes unchanging and that they are given to us exclusively by our parents, period. But we are learning that we also add and modify our genes as we age. We acquire one percent of our genes from bacteria, fungi, viruses and archae—single cell micro-organisms.  Specifically, there are special molecules that reside in these cells that are there specifically to develop antibodies. They are not part of the cell but act as independent contractors. Known as “plasmids” they help us fight infections. If we are constantly being infected, in order to help us develop immunity, they somehow insert their antibodies-producing-genes into our DNA so we can develop this protection ourselves. Sometimes our own genes change position in our chromosomes so they gain higher priority. These genes are known as “jumping genes” or as “transposons.”

Such strange genetic behavior was first discovered by Barbara McClintock in the 1940s who was awarded the Nobel Prize for medicine in 1983. How plasmid and jumping genes do this remains an absolute mystery. Her work provided evidence that the composition of our genes—our genome—changes while we are living. The longer we live, the more likely that these new genetic improvements are transmitted to our children. So now we have figured out the method of how Michael Rose’s flies create a time stamp on their genes. Plasmids are at work throughout the aging process.

We develop immunity from the day we are born and some of these biological adaptations end up in our genes through the transfer of external genetic material. Our genes are more permeable than we once thought. We get genes not just from our parents but also from the environment. In addition, we also get genetic material from our twins in the womb and mothers get genes from their children. We find male chromosomes in mothers who had baby boys. We are a magnet for adaptive genetic material from our environment.

Barbara McClintock was also the first scientist to correctly speculate on the basic concept of how some genes can be switched on and off—known as epigenetics, epi meaning “above” controlling genes. Sometimes a defective gene (e.g. for diabetes or Alzheimer’s disease) can be switched off—through diet, exercise and mild trauma. As we age we pick up new genetic material and modify existing genes (epigenetics) before we pass these genes on to our children. Our lives are devoted to just this aim, making sure that our children are best prepared to the new world they face. As for bad luck, we have Pandora’s last remaining attribute: Hope.

© USA Copyrighted 2018 Mario D. Garrett

References

Bartke, A., Wright, J. C., Mattison, J. A., Ingram, D. K., Miller, R. A., & Roth, G. S. (2001). Longevity: extending the lifespan of long-lived mice. Nature, 414(6862), 412.

Garrett M (2017) Immortality With a Lifetime Guarantee. Createspace.

Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993). A C. elegans mutant that lives twice as long as wild type. Nature, 366(6454), 461.

McClintock, B. (1993). The significance of responses of the genome to challenge.

Accessed:https://www.nobelprize.org/nobel_prizes/medicine/laureates/1983/mcclintock-lecture.pdf

Rebolledo-Jaramillo, B., Su, M. S. W., Stoler, N., McElhoe, J. A., Dickins, B., Blankenberg, D., ... & Paul, I. M. (2014). Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA. Proceedings of the National Academy of Sciences, 111(43), 15474-15479.

Rose, M. R. (1984). Laboratory evolution of postponed senescence in Drosophila melanogaster. Evolution, 38(5), 1004-1010.

The Religion of Aging: Finding Meaning

In a 2014 Pew Research Center study nine out of ten adults in the United States report believing in God and more than half are “absolutely certain” God exists. While one in five Americans pray every day, attend religious services regularly and consider religion to be very important in their lives. Although these proportions are declining precipitously since an earlier 2007 study, today religion still plays an important role in the lives of older people.

As adults get older they get more spiritual and some become more religious. It is not only that religious or spiritual people tend to live longer (they do, for many reason other than spirituality), but that older people become more spiritual and religious as they age.

There is a great attraction to argue for a spiritual interpretation of aging. Two religious gerontologists did just that when Jane Marie Thibault and Richard Lyon Morgan in 2012 made themselves their own subject matter when they wrote a book about their aging experiences. In a self-described pilgrimage into their third age, they interpret aging through religion. While growing up God has shown us how much he loves us by making us healthy, giving us pleasure through our bodies, nature, perhaps experiencing the miracle of having children. As we age then it is time for us to show God how much we love him in return. God stops showing us how great he made us and now it is our turn to reciprocate. In one example, by using “dedicated suffering,” we acknowledge our pain and dedicate it for the benefit of others. And it works. When people dedicate their suffering they report a reduction in pain. This spiritual switch—as older adults we are now responsible for the expression of gratitude—has some surprising support in the scientific field.

The Swedish sociologist Lars Tornstam in 1989 developed a theory that argued that older age brings about spiritual growth. Gerotranscendence Theory suggests that older individuals—perhaps because of ill health—tend to experience a redefinition of self and their relationships with others. By redefining ourselves we become more spiritually aware. More recent in 2009 the American Pamela Reed in developing her own Theory of Self-Transcendence states that individuals who face human vulnerability have an increased awareness of events that are greater than them. So is spirituality the answer to this increasing loss of control that we experience as we age?

Research tends to support this interpretation. In one review, the Portuguese researcher Lia Araújo and her colleagues, report numerous studies showing that religion, spirituality, and personal meaning have a broad range of mental and physical health benefits, satisfaction with life and coping better with stress. In older age, existential issues—contemplating life and death—appear to gain increasing importance. There seems to be a growing preference for acquiring meaning from faith. It seems that the greater the challenge the greater the religious or spiritual meaning that we gain from the experience. By gaining a positive meaning of life, purpose, religion, and spirituality individuals also gain a higher level of life satisfaction. Regardless of physical health, developing a positive attitude toward life has positive outcomes. It is only when religion becomes an ineffective tool for explaining dramatic challenges that people start revoking their religious conviction.

Christopher Ellison with the University of Texas at Austin and others have referred to this area of research as the “dark side of religion.” Doubt in our beliefs can have very negative consequences. Doubt erodes one of the major functions of religion which is to provide an explanation for why we are aging—such religious explanations are generally referred to as theodicies

But we are always looking for a reason, a model of the world that is just, logical and predictable. Religion has that extra facet of immortality—life in the afterworld, a comfort to those that have to confront the eminence of death. Whether we get this view of the world from religion, science or from intellectualizing, the overarching observation is that we need to have such a view. Everyone has an opinion on things that matter to them. Some simply don't call it religion but having an explanation comes with the territory of being human.

© USA Copyrighted 2018 Mario D. Garrett

References

Araújo, L., Ribeiro, O., & Paúl, C. (2017). The Role of Existential Beliefs Within the Relation of Centenarians’ Health and Well-Being. Journal of religion and health, 56(4), 1111-1122.

Ellison, C. G., & Lee, J. (2010). Spiritual struggles, and psychological distress: Is there a dark side to religion? Social Indicators, 98, 501–517.

Rogers, M. E. (1989). An Introduction to the Theoretical Basis of Nursing. Philadelphia: F. A. Davis

Rodin, J. (1986). Aging and health: Effects of the sense of control. Science, 233(4770), 1271-1276.

Thibault, J. M., & Morgan, R. L. (2012). Pilgrimage Into the Last Third of Life: 7 Gateways to Spiritual Growth. Upper Room Books.

Humility or Humiliation in aging, its your choice.

It is personal when it happens to you. As much as we talk about changes in older age, it remains at a distance, until it happens to you. Most of the time the loss of function happens fast and we are unprepared. While most of us might recover from an initial loss, we only have to face another different one shortly thereafter. Little pieces of you are taken away. And our mind does not deal well with these losses. You did not plan for it, and even if you thought of this eventuality, when it happens to you it is different. It is personal and real.

We have a model of the world in our brain. Within this perfect heaven there is our avatar, an image of us, who we think we are. As we get older and frailer—usually these come together—the reality conflicts with the avatar that we have built.  This model is important for us. Most of the time the model of the world and the avatar representing us functions well. We function on a daily basis without needing to be aware of this model. We behave in automatic mode most of the time. Until something goes wrong and the avatar can no longer do what its suppose to do.  The mental narrative that we have taken so long to build up suddenly needs to be re-arranged and re-modeled.

In aging, not long after the first of such redefinition of our model—perhaps we realize that we cannot read small print anymore without using prescription glasses—then comes another onslaught of loss. The constant change and attrition, requires us to be repetitively modify our model and our avatar. Aging is an existential danger to our model, because it threatens how that model is suppose to function. Making these changes is difficult for everyone since our model resists change, as it has been a faithful portrayal of our reality for so long. The older we get the more entrenched this model becomes. It is also doubly difficult in older age because there is so much variance among our peers. We delude ourselves that perhaps these attritions are only temporary and therefore we do not need to change our avatar just yet. There is always a lag in how old we are in reality and how old we see ourselves—a subjective age bias. Of course we are biased to see ourselves younger.

Many theories exist for why we underestimate our age. Overestimating our abilities, our looks, how satisfied we are in life, and aligning our personality, attitude, behavior and interests with that of a much younger person. Some theories also suggest that there is an internal bias to be young. But these theories assume that there is a conscious, if not willful desire to stay young. Although all these theories are valid, but there could be a simpler answer. There could be a lag, a time difference, between reality and how our model represents it. It takes time for us to reconcile reality. And the process is dynamic and we are continuously fighting this change. This dynamic process has not gone unnoticed.

In psychology by the 1950, Erik Erikson developed the first personality theory that included older adults. Before then most theories stopped at young adults. Erikson’s eight-stages of development comes closest to explaining this constant fight we experience in older ages. Likely written by his wife Joan Erikson, the final stage of development emerging late after age 65 years. This stage contests that there is a fork in the road. At this fork which Erikson called “crisis,” we either go towards ego integrity or we go headlong into despair. As dramatic as this crisis seems, it is emerging that such depictions are very close to the experience of aging.

By ego integrity Erikson means that we come to accept who we are. That we only have this life to live, and that we need to resolve issues in order for us to be able to be comfortable with where we are. Although seemingly diametrically apposed (ego versus non-ego) Lawrence Kohlberg’s 1973 theory of moral development later expanded to address older adults, included a stage of self-transcendence a “...contemplative experience of the nonegoistic or nonindividual variety” (p.500-501). Ego integration and non-ego seem to refer to the same concept, that of humility. The only salvation to older adults is becoming humble. John Cottingham in 2009 defines humility is, “ ... a lack of anxious concern to insist on matters of status, a recognition that one is but one among many others, and that one’s gifts, if such they be, are not ultimately of one’s own making” (p.153).

The alternate to humility is pride, when we are constantly fighting unresolved issues that continue to fester and create discord in our life. Later on Joan Erikson formulated a ninth stage of very old age that starts in the eighties when physical health begins to deteriorate and death becomes more real. She recognized at this stage that society similarly ups the ante, “aged individuals are often ostracized, neglected, and overlooked; elders are seen no longer as bearers of wisdom but as embodiments of shame” (p. 144). It seems that unless we subjugate ourselves to humility the alternate is humiliation.

That is why it is personal. Its not just about accepting aging, its that we have no choice. We either suck it up and become humble or fight it and face a certain humiliation. By sucking it up we acknowledge our mortality and therefore impermanence, our humility. If we fight it we rally our pride and confront these changes with certain outcome, failure and humiliation. Science tends to support this view. Neal Krause and David Hayward with the University of Michigan wrote that when it comes to humility, people that live the longest are the ones that accept where they are in life. By become less of ourselves (ego-less) nature rewards us with more of ourselves (long life.)

Someone has a dark sense of humor, and I hope that I live long enough to  learn to appreciate it.

© USA Copyrighted 2018 Mario D. Garrett

References

Cottingham, J. (2009). Why believe?. New York: Continuum. Erikson, E. H. (1956). The problem of ego identity. Journal of the American Psychoanalytic Association, 4(1), 56-121.

Kohlberg, L. (1973). Stages and aging in moral development—some explanations. The Gerontologist, 13, 497–502.

Krause, N., & Hayward, R. D. (2012). Humility, lifetime trauma, and change in religious doubt among older adults. Journal of Religion and Health, 51(4), 1002-1016.

Teuscher, U. (2009). Subjective age bias: A motivational and information processing approach. International Journal of Behavioral Development, 33(1), 22-31.

Aging Envy

An apology to Paul Dirac.

The basis of mathematics is "one"

But "one" does not exist in reality

It remains a construct of the mind.

Mathematics is a product of psychology

Patterns and rhythms that seem godlike

Even to some, music to our ears

Patterns we can hear and enjoy, comfort

Comfort reflecting more what we seek

Mathematics being the sign of divinity

A divinity that we seek as comfort to our search

Perhaps physics is all wrong, we need to examine our psychology first as post-modernist scholars before predicting the behavior of gods..