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article imageReview: Have researchers discovered the gene for aging? Special

By Victoria N. Alexander     May 31, 2016 in Science
Cracking the Aging Code: The New Science of Growing Old—And What it Means for Staying Young, by Josh Mitteldorf and Dorion Sagan, will be released June 14th, showing us how to increase the quality and quantity of our later years.
This engaging book has a threefold purpose: 1. To argue that group selection, not just individual selection, is at work in evolution by natural selection; 2. To argue that aging is an adaptation because the death of the individual is ultimately good for the larger group; 3. To suggest that if genes switch on aging, it might be switched off, for a decade or so, if not indefinitely.
Readers will want to get straight to point three, but it is not possible to properly judge the anti-aging recommendations in this book without understanding the root causes of how we start growing old and decrepit. What happens is the chemicals and hormones in your body that normally signal the destruction of unhealthy cells start to target healthy cells. Mitteldorf and Sagan explore many of the ways we might be able to correct or intercept these chemical signals — at least until that fateful day, sometime before a thousand years have passed, when we get hit by a bus or slip in the bathtub.
This 350-page book, published by Flatiron, a Macmillan imprint, presents some controversial ideas, not just about the causes of aging, but also about the process of evolution itself. Along the way, tells a story about how old science sometimes prevents the evolution of new science. Mitteldorf comes to the question from outside the field of biology, which enables him to see the unhelpful habits of thinking that evolutionists have gotten themselves into. Not stuck in the same rut of thought, he thinks more freely, if more confusedly at times. But, as we shall see, openness and uncertainly are sometimes the godparents of invention. He did not follow the familiar path of neo-Darwinists working on this question. He writes:
Faced with a new problem, I’m inclined to go for a long walk and allow my thoughts to sift, or to scratch equations in a notebook, or even to try a stripped-down example represented by numbers in a spreadsheet. Compared with Googling the answer, this process is terribly inefficient. It also leads me astray, and I get things wrong at least as often as I get them right. I continue in this way first because there is no satisfaction so sweet for me as engaging with a scientific puzzle. I rationalize the inefficient use of time with the hope that trying lots of wrong ideas and following them to the end gives conviction to my knowledge, and a depth to my understanding of how the world works.
The main code-cracking theory of this book is due to Mitteldorf, but co-author Sagan has also written extensively on the subject of death as biological adaptation (e.g., Death and Sex, 2009). I was at first surprised to learn that Mitteldorf was an astrophysicist, working mainly with numbers, before turning his attention to biology. But as we have seen so many times in science, it is often an outsider coming into the field that brings the freshest insights and moves research ahead in the most significant ways. Sagan is well-known for his innovative work, co-authoring many books with his mother, Lynn Margulis, the quintessential scientific rebel. Together Mitteldorf and Sagan slough off the old aging theories to make way for the new.
Point One
Cracking the Aging Code is part of a new tidal wave in evolutionary research that leaves the “selfish” gene theory (SGT) behind and is looking at different levels of selection, different kinds of selection and different sources of novelties caused by conditions and processes other than single-point mutations. SGT, a.k.a. neo-Darwinism, is associated with the faith that competition between individuals tends to favor the most fit. SGT ignores the evolutionary importance of cooperation among individuals, and it also tends to under-emphasize the fact that “fit” always means fit in an ecosystem, which must co-evolve with the individuals that live in it. The authors engage in what might be called an Oedipal struggle with the neo-Darwinists, but the fight is so badly mismatched that it is almost painful to watch SGT get pummeled by the facts. Virtually no contentious scrap of evidence remains of Dawkins’ legacy, built upon R. A. Fisher’s work, when this book closes. But what is a much more fascinating, to me, is the story of how SGT has continued to stay in the public consciousness, and at the receiving end of research grant applications, for so long.
In many ways Cracking the Aging Code reminds me of On the Origin of Species — both work to overcome entrenched ideas. The book starts with questions and it shows the author’s doubts along the way, his confusions, his embarrassments, his perseverance and finally the culmination of an idea. Mitteldorf is like a Darwin himself, full of questions about nature, plunging himself into thought against prevailing notions, making an intellectual voyage to the far ends of research to gather, with painstaking care, all the data needed to support the idea of group selection. For those readers who might not be aware of how scientific progress is actually made, I recommend this book because there is so much to be learned here from witnessing the struggle against orthodoxy, which is everything in science.
The SGT arose, according to the authors, not because the reality of evolutionary processes suggested it, but because, back in the 1930s and 1940s, Darwin's theory of evolution badly needed some empirical foundations to prove it true. Proofs tend to want numbers. As all those who have participated in school science fairs know, demonstrating a theoretical understanding of a complex process is not enough to win a ribbon. You must measure or count something. What you measure matters less than that the numbers support your conclusions. In the nascent stages of neo-Darwinism, practitioners realized that if they could locate a countable object — say, a single more fit gene — then it would be possible to prove, mathematically at least, that evolution does occur via natural selection of individuals with that gene.
It is somewhat remarkable that conclusions can be correct even when the steps leading up to the conclusions are incorrect. Fruitful science can continue, even with such a disadvantage, for a long while, but eventually tools are invented that enable the correct logical steps to the same conclusions to be worked out. And this is essentially what has happened in the field of evolution. Yes, Darwin was right, but not in all the ways he and later advocates thought he was. Single mutations are most probably not the focus of selection. It’s a lot more complicated than that.
Group selection is harder to quantify, harder to prove mathematically than individual selection, but this doesn’t mean it is any less true. Mitteldorf and Sagan mainly use logical arguments, recalling Darwin’s method, but Mitteldorf also presents mathematical models of simple predator-prey relations showing that the interacting populations fluctuate wildly when aging is not a factor and extinction is inevitable as the prey that is more fit for reproduction exhausts its resources. With aging added to the model, both populations stabilize, which indicates that aging offers an evolutionary advantage for the group, though not the individual. Also, as new fit individuals might be overcome by the sheer numbers of the older generation, clearing out the old stock lets new forms prove themselves, with greater adaptability overall as the result. Group selection seem essential for evolution to occur.
Point Two
Is aging an adaptation? Aging may be good for the species, and thus preserved by group selection, as Mitteldorf and Sagan show in addressing point one, but how do we know that aging is not inevitable?
Some organisms do not age; that is, as they increase in years, they do not become more likely to die by disease, by accident, by slowness, or weakness, nor do they become less fecund. In fact, some organisms become more fit the older they get. The question is then, which is the adaptation? Eternal youth or the tendency to age?
In addressing this issue, the authors first dispose of the rather poorly reasoned and nonetheless popular argument that bodies simply wear out like machines do. A defining characteristic of being alive is being capable of self-repair. The authors also point out that the more stress on the body, with caloric restriction and intense exercise, the less the body ages.
But if aging is not “wearing out,” it may be a kind of unraveling: every time a stem cell copies itself (in the process of self repair) a tiny bit of the tail end of the chromosome, called a telomere, is lost, and eventually the chromosome can become unstable. This condition may signal cells to start automatic self-destruction routines, which then spread to nearby cells. There are other factors that affect longevity, but telomere length may be the most significant.
Because the body can produce an enzyme, telomerase, that can lengthen telomeres — but only does so in embryos or, in some organisms, under certain other conditions — Mitteldorf and Sagan suggest that natural selection has fixed this nix on telomerase so that individuals do age and do die off faster, for the benefit of the larger population.
But if aging is the natural condition and it is beneficial at the level of the group, there would be no reason to assume that natural selection has had to fix a gene to actively suppress telomerase. We would only need to assume that natural selection, in most cases, never selected against the lack of telomerase, and in other cases, selected for anti-aging genes. However, the authors are fairly convinced that eternal youth is the natural state and aging is the adaptation, which would mean that the suppression of telomerase and/or perhaps other processes that trigger cell suicide are under genetic control and selected by evolution.
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Flatiron Books
Looking at the issue from a complexity science perspective, I consider the fact that all complex adaptive systems (e.g., tornadoes, autocatalytic reactions, and societies) naturally have lifespans: they emerge, grow, learn, form habits, become too rigid and then to begin to break apart (See Stanley Salthe, Development and Evolution: Complexity and Change in Biology, 1993; Eric D. Schneider and Dorion Sagan, Into the Cool: Energy Flow, Thermodynamics, and Life, 2006). They do so without the control of genes. Although living organisms do have genes, they are also complex adaptive systems. Life is a collection of interacting self-organized chemical reactions (made possible by the physical structures that grow with the aid of inherited DNA templates). Based on Sagan's previous work in this area, I would have supposed that aging is not genetically determined but is a side-effect of acquiring self-organized habits that enable intelligent and purposeful behavior. Experience tends to strengthen habits (i.e., signaling pathways) and this tendency over time leads to rigid behavior. While cells are replaced year after year (and this is how life stays young), what continues for each unique individual, defining it as such, are its learned patterns of activity. Perhaps it is the growing inflexibility that leads to aging and to the dissolution of the system. In this case, aging would be neither the breakdown of the physical parts nor the action of suicide genes, so much as the loss of flexibility in the “epigenetic states,” as the authors call the body’s habits. If old signalling pathways are reacting either too generally or too narrowly to signs, then this might explain why signaling goes awry in older people.
The biological signaling pathways of an older person may be just like your old uncle Fred’s or aunt Bertha’s politics: they label everyone (either as a free-market-worshiping Republican or as a nanny-state-loving Democrat) and they fail to properly recognize real friends and foes. Those fruitless conversations your family has at Thanksgiving, that may be what aging is like in the body’s immune system: reactionary, bull-headed, close-minded and stubborn, indiscriminately attacking good ideas and praising poor ones. The cure, if there is any, would be some unlearning, introducing openness to new ideas. In fact, healthy epigenetic states might resemble Mitteldorf’s unprejudiced and uncertain approach to investigation described above.
But whether we should seek to disable a gene that turns aging on or turn on a gene that starts anti-aging, or trick the body into being reasonable again, we do not quite know, say the authors. There do appear to be anti-aging genes that trigger processes that keep habits flexible in eternally young turtles, lobsters, flatworms and sea urchins. Famine and physical stress do appear to trigger genes that prevent aging, perhaps controlling telomerase expression or thymus growth. The book suggests ways to approach this, but its complicated; a myriad of signals seem to be involved in aging. While researchers look for master signals that control entire cascades of signals, our authors soberly note that there may be “hundreds of signals, all intertwined and controlling the body’s age state … with no hierarchy with a few on top controlling many on the bottom.” Nevertheless, some methods have been discovered that you can try now to add another decade of healthy living to your time.
Point Three
How do we stop aging? Or at least slow it down? Although such questions have been asked for millennia and answered too readily by quacks and charlatans, according to the authors, we are now in a position to say that, to some extent, aging can be controlled. Some approaches involve commonsense diet, vigorous exercise, and intermittent fasting. The book explains the potential benefits of a daily dose of aspirin, fish oil, curcumin supplements (from turmeric), fifty times the recommended daily allowance of Vitamin D, astragulas root, and melatonin. Other approaches, such as using the prescription drug metformin and hormone/gene therapies, are described and critiqued.
Although some progress in theories of aging has certainly been made, the authors acknowledge that there is no easy fix for systemic failure of biological signaling. They realize that to stop the aging process the body’s “intelligence” needs to be restored. The normally beneficial processes of inflammation and apoptosis, which eliminate unhealthy cells, must be stopped from destroying healthy cells. This might be as difficult as convincing your uncle Fred to vote for an outsider like Jill Stein or Gary Johnson for President in 2016, but maybe not impossible.
Conclusion
If aging — the tendency to become sick, weak, forgetful, wrinkled, disabled, hardheaded — could be stopped, and yet death still come as frequently as ever, then anti-aging research would not potentially feed the human population explosion. In the end, the authors consider that anti-aging research might ultimately result in our extinction. Increased longevity must go hand-in-hand with some serious family planning and ecosystem conservation.
We might want to abolish seat-belt and helmet laws and offer tax incentives for professional skydivers and stuntmen too.
More about theory of aging, Antiaging, gene for aging, Evolution, aging gene
 
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