Aging and the geroscience hypothesis

post by DirectedEvolution (AllAmericanBreakfast) · 2023-07-12T07:16:04.516Z · LW · GW · 14 comments

Contents

  Cautionary introduction
  The nature of aging and the geroscience hypothesis
    Point #1: There is no need to speculate that evolution is making you age “on purpose” or that it's already endowed us with the longest, healthiest lives possible.
    Point #2: There’s a difference between aging and extrinsic causes of death, but they interact.
    Point #3: Our bodies can repair themselves, but in almost all organisms, that self-repair ability is limited and declines with age.
    Point #4: Your genes only care about your survival insofar as it helps you to reproduce.
    Point #5: Old age is a side benefit of reaching childrearing age, but none of that matters unless fertilized eggs are perfectly fresh every single generation.
    Point #6: You’re designed to fall apart from aging more or less all at once, at about the point in life when our caveman ancestors became a burden or died by predators and disease.
    Point #7: Evolution is optimizing for childrearing, sometimes at the expense of health in old age.
    Point #8: A powerful way to improve human health and wellbeing might be to treat the hallmarks of aging before they manifest as disease.
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Cautionary introduction

I am a biomedical engineer with an interest in the science of aging. The Handbook of the Biology of Aging, 9th ed, is a great 400-page introductory resource, looking at aging on every level from evolutionary and conceptual, to public health, to specific molecular and organ systems, to genetics, to immortal organisms.

My goal is to teach readers key concepts and facts about aging research in short posts with accessible language. I follow the substance of the handbook chapters, though I sometimes reorganize them. I'm also presenting the chapters out of order, because I think it creates a better narrative. I encourage readers to take the facts and concepts tentatively - they are just pointers to a rich and sometimes controversial underpinning literature. My hope is that some readers will go on to read the handbook and explore the literature it cites.

Chapters will be presented out of order in order to improve the overall narrative flow. This post is for chapter 4:

Hornsby, P. J. (2021). The nature of aging and the geroscience hypothesis. In Handbook of the Biology of Aging (pp. 69-76). Academic Press.

Next: Compression of morbidity [LW · GW] (available 7/12/2023)

The nature of aging and the geroscience hypothesis

This chapter is about making sense of a seemingly paradoxical thesis:

The fact that aging and injury are inevitable should encourage us about the possibility of advanced medicine that makes frailty and death preventable.

Your body is made of physical stuff - DNA, proteins, sugars, fats, cells, tissues, and organs - and physical stuff, left alone, inevitably breaks down and becomes disordered. The longer you live, the more chances you take with car crashes, disease, and other external causes of death. Aging is entropy - the inevitable process by which the laws of physics guarantee that a system will become disordered over time.

Yet the entropy of aging and injury is something we fight every time we heal a wound (or for that matter, repair a car or clean the house). Physics also tells us that we can repair the damage of aging and injury as long as we have the skill and energy to do so.

The fact that physics guarantees we'll experience aging and injury means we can reject the idea that aging is somehow directly beneficial to us or to our species. By Occam's Razor^[1], there's no need to suppose some evolutionary benefit from aging and injury, since they're already explained perfectly well by entropy.

Yet as we'll see, not all evolutionary pressures tend in the direction of longer, healthier lives, so we can't expect that evolution has already taken every opportunity to preserve our health for as long as possible.

Together, these facts are encouraging. They mean that we can reject the pessimistic notions that evolution has already endowed us with the longest, healthiest lives possible, or that frailty and death are the inevitable results of entropy^[2]. Therefore, modern medicine has plenty of scope to add new maintenance and repair abilities to those our bodies already possess.

Point #1: There is no need to speculate that evolution is making you age “on purpose” or that it's already endowed us with the longest, healthiest lives possible.

Of course, you can die from a disease, predator, car accident or gunshot wound, not only by aging. Aging can make you more vulnerable. But there’s a meaningful difference between being eaten by a shark, succumbing to pneumonia after years of declining health, and dying peacefully in your sleep at age 102.

Point #2: There’s a difference between aging and extrinsic causes of death, but they interact.

We can overcome the extrinsic damage and gradual aging of our houses, cars and clothing with cleaning, maintenance and repair. The bodies of living things largely clean, maintain and repair themselves: old stained proteins are broken down and new ones are built, our kidneys constantly filter the toxins and byproducts that build up in our blood, and our cells regrow to heal wounds. Yet repair typically means that we remove some broken, worn-out part and replace it with fresh material, whether we’re talking about replacing the roof on our house or replacing the outermost layer of our skin cells.

Unfortunately, most, if perhaps not quite all, living things can only repair themselves for only so long. Who will repair the repairers? Stem cells split into two new cells: a fresh stem cell and a copy that matures into a replacement skin cell, for example. But that “fresh” stem cell isn’t perfectly fresh. It has aged a bit. Eventually, your body is full of old stem cells, trying to replace still more aged mature skin, kidney, eyeball and brain cells.

Point #3: Our bodies can repair themselves, but in almost all organisms, that self-repair ability is limited and declines with age.

The whole succession of your ancestors and descendents, including you, is an immortal germ line. Your individual physical body is merely a way of perpetuating it, and that makes you a disposable soma. The genes encoded by your DNA are using your body as a tool to perpetuate themselves, and they have been doing so successfully for billions of years. They’ve realized that the key thing is to get their host to make children. They have no loyalty to their host, and will gladly sacrifice their host’s health if it helps with the reproduction and survival of children. 

Point #4: Your genes only care about your survival insofar as it helps you to reproduce.

The worst thing that can possibly happen to your genes is that you fail to reproduce. The best way to ensure you’ll survive to childrearing age is to build you sturdy enough to survive well past it, into middle and old age. Almost as bad as failure to reproduce would be a decline of the germ line over the generations. Every budded bacterial or fertilized egg has to be equally fresh, perfectly restored, despite being made from the deteriorating cells of the soma, your aging body.

Point #5: Old age is a side benefit of reaching childrearing age, but none of that matters unless fertilized eggs are perfectly fresh every single generation.

If virtually all your ancestors died from disease, predators, or injury by age 80, evolution saw no point in trying to build you to survive much beyond that age. If everybody’s hearts gave out at age 40, there would be no point in evolving lungs that can survive to age 80. As a result, evolution has resulted in us having organs that all have about the same life expectancy, which is roughly balanced with when our ancient ancestors would have died from extrinsic causes or been useless for bearing and rearing children. 

Point #6: You’re designed to fall apart from aging more or less all at once, at about the point in life when our caveman ancestors became a burden or died by predators and disease.

Let’s say a gene makes you a bit healthier in old age. The benefits won’t show up until after you’re no longer capable of bearing children. That means that unless your improved health helps your children survive and reproduce, that gene misses out on natural selection and will eventually drift out of the genetics of your descendents. If that gene also comes with a tradeoff that makes you a bit less fertile or healthy in youth, however, it will be heavily selected against by evolution. A gene that makes you more fertile and healthy in youth, but at the cost of suffering in old age, will be favored by evolution. This evolutionary favoritism of the young is termed antagonistic pleiotropy.

Point #7: Evolution is optimizing for childrearing, sometimes at the expense of health in old age.

Certain hallmarks of aging show up in every tissue in the body. Your immune system goes haywire. Healthy proteins are torn apart by reactive byproducts of energy production in the cell or get crusted up by sugars. Cells start making the wrong mix of proteins, their mitochondrial powerhouses break down, or they get so disorganized that they shut down and start spewing out weird chemicals. The FDA doesn’t recognize these as diseases, per se, but we have good reason to think they are the fundamental problems that lead to disease and death. To what extent does a healthy diet and exercise, stress management, and clean air make us live longer by avoiding these destructive underlying issues? Can we slow or prevent many diseases at once by treating these underlying issues? We call this idea the geroscience hypothesis.

Point #8: A powerful way to improve human health and wellbeing might be to treat the hallmarks of aging before they manifest as disease.

1. ^{^}

   The principle that we should reject layering on unnecessarily complex extra hypotheses when we already have a stronger, simpler explanation for what we observe.

2. ^{^}

   On the order of thousands or millions of years, anyway. Live long enough and the whole universe will turn to dust, and there's nothing we can do about that.

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