{"id":145,"date":"2013-09-23T20:18:43","date_gmt":"2013-09-23T20:18:43","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=145"},"modified":"2013-09-23T20:18:43","modified_gmt":"2013-09-23T20:18:43","slug":"aging-and-life-extension-unexpected-lessons-from-evolution","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/09\/23\/aging-and-life-extension-unexpected-lessons-from-evolution\/","title":{"rendered":"Aging and Life Extension: Unexpected Lessons from Evolution"},"content":{"rendered":"

This is the text of a brief presentation that I delivered yesterday in DC at a symposium on radical life extension<\/a>. \u00a0In a new experiment (for me), I’ve prepared a self-presenting powerpoint<\/a>, with voice and images\u00a0that you can view either with PPT software or as a Youtube video<\/a>.<\/em><\/p>\n

——————————<\/p>\n

In the old view of aging<\/a>, evolution has neglected her children in old age because in the wild, hardly anyone ever survives to old age. So the body is permitted to fall apart. Damage accumulates. The body wears out like an old machine.<\/p>\n

Another part of this picture is that all the stresses of modern life are accelerating aging. \u00a0Pollution, pesticides, radiation, and high-fructose corn syrup are stresses that the body just wasn\u2019t evolved to cope with, and they wear us down faster, shortening our life span.<\/p>\n

But in the 1990s, evidence against this picture began to accumulate. For one thing, aging takes a huge bite out of fitness in the wild<\/a>. Animals do<\/em> live long enough for aging to be a factor in the death rate. For another, people are not cars. A car wears out faster the more you drive it. \u00a0But our bodies respond to stress by overcompensating so that the more active we are, the longer we live. Animals too, live longer with intense exercise. It\u2019s called \u201chormesis\u201d. Other kinds of stress, like starvation and certain toxins, radiation, infections, heat and cold also increase life span, paradoxically. If the body were just wearing out, this would be very hard to explain.<\/p>\n

A third point against the theory is that genetic scientists began to discover \u201caging genes\u201d. I define an aging gene to be one that can be deleted with genetic engineering and the animal lives longer without it. Dozens of such genes are known now in every lab species where they have been sought. The record is for a gene known as AGE-1 in lab worms. When both copies of this gene are knocked out, the worms\u2019 lives are extended tenfold.<\/a><\/p>\n

A completely unexpected thing about these genes is that they come in families<\/a> that span the entire biosphere. \u00a0Genes for aging in you and me are closely related to genes for aging in the fruit fly and the worm and even primitive yeast cells. This can only mean that aging genes are evolutionarily conserved. That is, they are an adaptation, a product of natural selection.<\/p>\n

Aging is programmed into our genes as an adaptation<\/strong><\/p>\n

Evolution has arranged for us to die on a schedule. \u00a0We have genes with no other purpose than to destroy us. Suicide genes<\/a>. Our bodies don\u2019t wear out despite nature\u2019s best efforts to protect us. On the contrary, aging is an active process of self-destruction, bequeathed to us by nature, programmed into our genes.<\/p>\n

(One implication of this is that the selfish gene<\/a> version of evolutionary theory is a very narrow window, defining one small part of how evolution works \u2013 but that\u2019s a story for another day.)<\/p>\n

 <\/p>\n

No such thing as “natural anti-aging”<\/strong><\/p>\n

If you believe the old view, then nature is our friend. Our bodies are doing their best to resist the ravages of aging, and our job is to help the body out. Natural foods, in particular, support the body by giving it the fuel that it was evolved to work with. Low stress and a slower pace help preserve the body. Eat organic.<\/p>\n

But in the new picture, moderate stress prolongs life span. Hunger is good for us<\/a>. Intense exercise that makes us feel like we can\u2019t stand it is one of the best things we can do for ourselves. Even poisons<\/a> can promote longevity.<\/p>\n

How can this be, that the body does so much better at forestalling aging when it is stressed?<\/p>\n

 <\/p>\n

What adaptive purpose is served by death on a schedule?<\/strong><\/p>\n

There\u2019s an evolutionary story behind it which is the centerpiece of my own research. The reason that aging evolved is to take control of the death rate, to level it out so everyone doesn\u2019t die all at once. In nature, starvation is the biggest threat to life. And it tends to kill everyone at the same time. When there\u2019s no food for me, there\u2019s probably no food for you either. There\u2019s a famine and we all die together. This is called extinction. Not good for evolution.<\/p>\n

Aging evolved for the purpose of helping to avoid population overshoot<\/a>, to level out the death rate so the ecosystem can find its equilibrium. In this way, aging protects against extinctions. When there\u2019s plenty of food and no one is dying of starvation, that\u2019s when nature needs aging, to help raise the death rate. But when food is really scarce and some are dying of starvation, more death (from old age) is the last thing the ecosystem needs. So aging takes a vacation when the population is stressed.<\/p>\n

This is the reason that things that prolong our lives tend to be uncomfortable. \u00a0We need to send the body stress signals to suggest that there\u2019s already plenty of death in the air, and then aging will loosen its grip on us.<\/p>\n

 <\/p>\n

Implications for ROS theory and oxidative damage<\/strong><\/p>\n

In the old view, oxidative stress is the enemy, a kind of rusting from the inside out. But in the new view, oxidative stress is part of the signaling that tells the body to protect itself. \u00a0Anti-oxidants – vitamins A, C and E were tried and tried, in animals and in humans – and they actually increase mortality<\/a>. \u00a0Intense exercise, on the other hand, generates loads of free radicals and it\u2019s actually the free radicals that signal the body to go into a protective state. Taking anti-oxidants before you exercise can nullify some of the benefits<\/a>!<\/p>\n

So what\u2019s the message that evolution has for us concerning how we can live longer? \u00a0Three things:<\/p>\n

    \n
  1. \n

    \u00a0\u201cNatural Anti-aging\u201d is an oxymoron<\/em><\/p>\n<\/li>\n

  2. \n

    There is a shortcut to life extension based on hormonal signaling.<\/em><\/p>\n<\/li>\n

  3. \n

    As life extensionists, we are advocates for conservation and birth control.<\/em><\/p>\n<\/li>\n<\/ol>\n

    We\u2019ve already talked about #1. There is no such thing as \u201cnatural anti-aging\u201d. Aging itself is natural. We can only extend life span by fighting with nature, manipulating or tricking evolutionary programs. \u00a0We do this with exercise, with hormesis, with caloric restriction and its mimetics. But that trick is limited to the built-in buffer that nature has provided \u2013 probably 5 to 10 years of extra life.<\/p>\n

    \"AgingClock\"<\/a><\/p>\n

    To go beyond 10 years, #2 is deeply promising. The old view was pessimistic. Since evolution has already done its best for long life, we\u2019re going to have to think of something that evolution hasn\u2019t been able to come up with in a billion years. But if we think that our genes have a built-in death program, then all we have to do is to thwart that biochemical program. Turn it off. Throw a monkey wrench into the suicide machine.<\/p>\n

    Interfering with biochemical pathways is something that the pharmaceutical industry is really good at. Hormones and receptors are lock and key molecules. You make a molecule that sticks in the receptor, and this blocks the action of the hormone. This approach to anti-aging is very promising.<\/p>\n

    In this new picture, where aging is programmed self-destruction, the body must have some way of knowing how old it is. This implies that there is an aging clock<\/a>, or more likely, several redundant clocks. There is the very exciting promise that we might be able not just to slow down the aging clock, but to reset the hands to a younger state.<\/p>\n

    The one aging clock that we already know about is telomere length. \u00a0I have written in this column<\/a> about telomeres, and you have heard the story elsewhere, I\u2019m sure. With every cell division, our stem cells lose a little DNA, from the tail of each chromosome. Telomere length is inversely related to mortality, in humans and in animals. Short telomeres contribute to all the diseases of old age.<\/p>\n

    There are several herbal products available NOW [1<\/a>,2<\/a>,3<\/a>,4<\/a>] that offer some ability to lengthen telomeres. Enough to slow the clock, but not enough to actually set the hands back. There is research going on in several private companies, seeking ways to do a better job of re-setting the telomere clock using designer chemistry. \u00a0The best lab that I know of is Sierra Sciences<\/a>, and they are presently stalled for lack of funds – a great opportunity for investors to step forward.<\/p>\n

    We know that telomere length is an important clock, but we also know that it is not the only biological clock. A hot topic in research the last year or so is the epigenetics of aging<\/a>. \u00a0Which genes are active and which are inactive? This is \u201cgene expression\u201d and it changes with age. I have floated the idea just this year that gene expression constitutes a powerful aging clock. That if we can direct the old body to activate a young gene profile, then the body will respond by turning itself young.<\/p>\n

    You might think that there\u2019s some kind of \u201cyouth serum,\u201d something the body isn\u2019t able to make when it\u2019s old that it used to make when it was young. But the fact seems to be more the opposite: that there are blood factors that the body makes when it\u2019s old but not when it\u2019s young that are turn on the suicide program.<\/p>\n

     <\/p>\n

    Life Extension must be Balanced with Conservation and Population Control<\/strong><\/p>\n

    #3 is my final message to you. You and I are part of a community dedicated to extending the human life span. We are succeeding, and this is a wonderful thing for every individual who receives the benefit. But evolution tells us that in addition to individual good there is a separate collective good. What is good for every individual may be disastrous for the community. This is the tragedy of the commons<\/a>.<\/p>\n

    In fact, aging evolved for the purpose of controlling population overshoot. \u00a0For 150 years now, humans have succeeded in extending our life spans<\/a> worldwide. The individual result has been an enormous lifting of a burden of suffering and fear of untimely death. \u00a0But the collective result has been that humans are a blight on the biosphere. The rate of extinction is unprecedented<\/a> – higher even than the great dinosaur die-off of 65 million years ago. There are resources that were built up over millions of years, and we\u2019re using them up as if they belonged to us, with no consideration of future generations, or other life forms.<\/p>\n

    We, as the world\u2019s top predator, depend on a diverse ecological base of plants and animals, ocean and land species, insects, algae, plankton, bacteria\u2026 If we destroy that base, we destroy ourselves. And we are destroying it, with reckless abandon. People who imagine that the world can be turned into a great farm to support tens of billions of humans understand nothing about ecology. \u00a0The robustness of the natural world depends on diversity.<\/p>\n

    \"Earth-hands\"<\/a><\/p>\n

    If our dream of extending human life span is not to turn into a nightmare of famine and resource wars, then you and I must split our time between promoting life extension and promoting (1) conservation – the environmental footprint of each human, and (2) population control, bringing down the birth rate to match the falling death rate.<\/p>\n

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    This is the text of a brief presentation that I delivered yesterday in DC at a symposium on radical life extension. \u00a0In a new experiment (for me), I’ve prepared a self-presenting powerpoint, with voice and images\u00a0that you can view either with PPT software or as a Youtube video. —————————— In the old view of aging, … Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-145","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"\nAging and Life Extension: Unexpected Lessons from Evolution - Josh Mitteldorf<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/09\/23\/aging-and-life-extension-unexpected-lessons-from-evolution\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Aging and Life Extension: Unexpected Lessons from Evolution\" \/>\n<meta property=\"og:description\" content=\"This is the text of a brief presentation that I delivered yesterday in DC at a symposium on radical life extension. \u00a0In a new experiment (for me), I’ve prepared a self-presenting powerpoint, with voice and images\u00a0that you can view either with PPT software or as a Youtube video. —————————— In the old view of aging, ... 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. This makes the mechanism challenging to understand and to model. more at http:\\\/\\\/mathforum.org\\\/~josh\",\"sameAs\":[\"http:\\\/\\\/AgingAdvice.org\"],\"url\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/author\\\/joshmitteldorf\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO Premium plugin. -->","yoast_head_json":{"title":"Aging and Life Extension: Unexpected Lessons from Evolution - Josh Mitteldorf","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/09\/23\/aging-and-life-extension-unexpected-lessons-from-evolution\/","og_locale":"en_US","og_type":"article","og_title":"Aging and Life Extension: Unexpected Lessons from Evolution","og_description":"This is the text of a brief presentation that I delivered yesterday in DC at a symposium on radical life extension. \u00a0In a new experiment (for me), I’ve prepared a self-presenting powerpoint, with voice and images\u00a0that you can view either with PPT software or as a Youtube video. —————————— In the old view of aging, ... 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. 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