Friends often look at me quizzically when I tell them this. \u00a0One says, \u201cBut I can feel myself wearing down.\u201d And another: \u201cNothing works the way it used to. \u00a0Isn\u2019t that the definition of wearing out?\u201d \u00a0And again: \u201cDo you mean it\u2019s all in my head, it\u2019s not really happening?\u201d and then a moment later, \u201cdo you mean it doesn\u2019t have to be this way?\u201d<\/p>\n
This last formulation is getting a little closer to what I mean.<\/p>\n
Of course, loss of function with age is not just in your imagination, and it is very common (though not universal!) in the Animal Kingdom. \u00a0But aging is not caused by wearing down. \u00a0It is more accurately an orderly program of self-destruction, orchestrated by gene expression. \u00a0Some aspects of aging appear as accumulated damage (e.g. cartilage worn away from joints, or build-up of cross-linked sugar-protein complexes), but on closer inspection even these are seen to be entirely avoidable consequences of the body shutting down its repair systems.<\/p>\n
This column is devoted to the reasoning and the evidence that tells us aging cannot be, at root, a process of wear and accumulated damage. \u00a0First, the theory: why there is no physical necessity for aging; second, a few examples of animals that age very slowly or not at all, and others that age super-fast; third, some familiar facts and a few unfamiliar facts about aging that tell us \u201cwearing out\u201d does not provide a helpful perspective.<\/p>\n
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1. The Physical Theory, and Why it Doesn\u2019t Apply to Living Things<\/strong><\/p>\n There is no physical necessity for aging.<\/p>\n Man’s earliest conception of aging was that the process was akin to physical wear and tear. Knives get dull – why shouldn’t our teeth? \u00a0Wheels get rusty and squeak when they turn – isn\u2019t that what happens to our joints? \u00a0Water pipes fill with sediment over the years, just like our sclerotic arteries. \u00a0It’s a theory with a great deal of intuitive appeal.<\/p>\n But the analogy between living body andmachine is flawed. \u00a0Living things are fundamentally homeostatic. \u00a0They can repair themselves. \u00a0They build themselves from a single egg cell, and simple animals can rebuild when damaged. \u00a0A car takes in energy in the form of gasoline and uses the energy to propel itself forward. \u00a0An animal takes in energy in the form of food and uses it to perform all the feats of metabolism, locomotion, foraging, signal processing, and evasion of predators; and a small portion of that energy is devoted to the \u201ccapital budget\u201d: breaking down and rebuilding damaged tissues; replicating cells; looking for copying errors in DNA and setting them right, detecting malformed protein molecules, breaking them down into constituent peptides for recycling into new molecules. \u00a0This small part of the energy budget is all that is needed to keep the system in good repair indefinitely.<\/p>\n The Second Law of Thermodynamics<\/a> says that entropy (disorder, degeneration, damage) must increase in any isolated physical system. \u00a0But living systems are not isolated. \u00a0Living things draw free energy* from their environment, use it internally, then dump waste entropy back into the environment.<\/p>\n This isn\u2019t some lucky feature, tacked on to living bodies, rescuing them from an ironclad law of physics. \u00a0The capacity for homeostasis is built into the form and function of living things. \u00a0To a physicist, a living body is defined by its ability to create and maintain itself using ambient sources of free energy. \u00a0The very function of the living machine is homeostasis (along with reproduction).<\/p>\n Q:<\/strong> \u00a0Even though the body is able to repair itself, the repair can\u2019t be perfect. \u00a0Isn\u2019t that the root cause of aging?<\/em><\/p>\n A:<\/strong> \u00a0The repair doesn\u2019t have to be perfect. \u00a0The body built itself from seed, created a robust, young individual in the prime of life. \u00a0But the body wasn\u2019t perfect when it was young. \u00a0Repair can be accomplished to that same standard. \u00a0In fact, it\u2019s always easier to repair a body than to build a new one from scratch.<\/p>\n Q:<\/strong> \u00a0When a car gets old, it becomes more and more costly to repair. \u00a0Eventually, the mechanic tells you that it\u2019s going to cost you more to fix all the things wrong with your car than to buy a new one.<\/em><\/p>\n A:<\/strong> \u00a0This is an artifact of mass production. \u00a0A new engine is made on an Asian assembly line, with low labor costs and automated manufacture. \u00a0Repair requires local, skilled labor, paid at a rate reflecting professional service. \u00a0Cars are loss-leaders, artificially cheap; replacement parts are expensive when the manufacturer knows you\u2019ve got no place else to go. \u00a0Most important, an engine must be disassembled bolt-by-bolt to get at the worn piston rings deep inside, then meticulously rebuilt; but living tissues are repaird from the inside by efficient molecular machines.<\/p>\n Q:<\/strong> \u00a0But think in terms of information. \u00a0The DNA is like a book that needs to be copied over and over. \u00a0If a single letter is mis-copied, and it evades the error-checking machinery, that represents lost information that can never be recovered. In the long run, the errors have to accumulate, and eventually they will degrade the cell\u2019s ability to function.<\/em><\/p>\n A:<\/strong> \u00a0This is true, and was the basis of a promising theory of aging in the 1960s. \u00a0Experiments were done to test this theory, and it didn\u2019t pan out. \u00a0It turns out that DNA replication is designed to be accurate enough that the errors accumulating over one lifetime are not a significant problem. \u00a0I wrote up this topic recently<\/a>, as\u00a0a new study was done based on 100-year-old twins, and found that only an insignificant handful of mutations over a long lifetime.<\/p>\n When stem cells divide to form new, differentiated cells, the old, original strand of DNA stays with the stem cell and the newly-copied strand goes consistently with the differentiated cell. \u00a0It seems that Nature has been thinking about DNA copying errors, and has taken care of the problem.<\/p>\n So yes, some loss of information is inevitable over long enough times but no, this is not relevant to aging. \u00a0Read more here.<\/a><\/p>\n Aging can\u2019t be explained by inevitable accumulation of chemical damage, or DNA copying errors that accumulate, or physical wear and tear, or the accumulated toxic effects of reactive oxidative by-products of the energy metabolism (ROS). \u00a0Actually, this much was understood already at end of the 19th Century, when August Weismann<\/a> wrote a book attempting to explain aging from an evolutionary perspective.<\/p>\n <\/p>\n 2. Aging in nature: fast, slow, and backwards<\/strong><\/p>\n Aging appears in nature in an amazing variety of forms. \u00a0Some of these were abstracted as graphs in a paper I reviewed last month<\/a>. \u00a0In our anthropocentric view, we might imagine that all animals grow up, reproduce in the prime of life, then gradually lose fertility and strength, and suffer accelerating decline leading to death. \u00a0This is the way it is for people, guppies, and sea birds.<\/p>\n But salmon and octopuses reproduce all in a burst and quickly die. \u00a0The thing that kills the salmon is a burst of corticoid hormones that deranges the fish\u2019s hormonal balance. \u00a0What kills the octopus is that its mouth seals closed, and it can no longer eat.<\/p>\n Sharks and clams just keep growing larger and more fertile and stronger and less vulnerable to death as they get older. \u00a0The oldest ones are rare and large, and it takes a great accident to kill them, because they are not about to die of old age.<\/p>\n Cicadas spend 17 years maturing underground, then come out, mate and die in a single day. \u00a0The adult has no organs for eating or digesting food.<\/p>\n Some jellyfish and beetles have been observed to regress when starved. \u00a0Their bodies shrink, then progress backward through previous stages of development until they are larvae once more. \u00a0As larvae, they can exist in a kind of hybernation, and when food becomes available, they can grow again and start life over. \u00a0In the lab, they have been manipulated to go through many cycles of getting older, getting younger, and on and on.<\/p>\n Rockfish are medium-sized, deep water dwellers. \u00a0Though most rockfish live 10 to 20 years, occasionally one is caught that is over 200 years old, as determined by annual growth rings in an ear bone.<\/p>\n The fastest life cycles in nature (yeast cells) suffer aging and death in a matter of hours. \u00a0The slowest (sequoia trees) aging processes unfold over thousands of years. \u00a0If aging is an inevitable physical process, why would it occur a million times faster in some species than in others?<\/p>\n It would appear that aging is a common but optional part of the life plan.<\/p>\n <\/p>\n 3. Response to stress: \u00a0Aging doesn\u2019t act as we would expect<\/strong><\/p>\n If you keep your car in the garage six days a week and drive only to church on Sundays, it will last a long time. \u00a0Drive it like a hot rod and it will wear out a lot sooner. \u00a0But our bodies last longer the harder we work them.<\/p>\n Exercise generates free radicals like crazy, but the body\u2019s native anti-oxidant defenses overcompensate. \u00a0Muscles suffer little tears, bones tiny fractures, and yet the body repairs these better than new, and the result is that we live longer if we exercise.<\/p>\n One of the three mainstream evolutionary theories (the \u201cdisposable soma\u201d) holds that aging results from budgeting of energy. \u00a0The body apportions its food energy for maximal fitness, not for maximal longevity, so more of it goes to survival and reproduction, less to repair and maintenance. \u00a0This theory is utterly untenable in the face of caloric restiction experiments. \u00a0Animals quite generally live longer ther less they are fed. \u00a0If aging were enforced by the energy budget, a larger energy budget would cause us to live longer.<\/p>\n Finally: Some of the biochemistry of aging is understood now, and its basis looks like self-destruction, not like attrition.<\/p>\n Stem cells cease replicating when their telomeres become too short, all because the enzyme telomerase is withheld.<\/p>\n<\/li>\n Inflammation<\/em>, which protects the young body against invading microbes, is turned against healthy tissues in old age, damaging arterial walls in particular and triggering cancers everywhere.<\/p>\n<\/li>\n Apoptosis<\/em> is cell suicide, which works to protect us against diseased and dangerous cells in our youth, but as we get older we lose healthy, functional cells to apoptosis. \u00a0This is the underlying cause of sarcopenia, and is related to the cause of Alzheimer\u2019s disease.<\/p>\n<\/li>\n The thymus<\/em> is a tiny gland at the base of the throat, responsible for training white blood cells so that they are smart enough to attack invading pathogens and refrain from attacking the body\u2019s own tissues. \u00a0As we age, the thymus shrinks in size and loses its functionality, so the immune system makes errors Type I and Type II: \u00a0It attacks the self, causing auto-immune diseases including arthritis, and it fails to attack invaders, making us increasingly vulnerable to infectious disease.<\/p>\n<\/li>\n<\/ul>\n <\/p>\n The bottom line<\/strong><\/p>\n Since 1889, mainstream evolutionary science has rejected the idea that the body ages for the same reason that a tool or a machine wears out. \u00a0In this case, evolutionary science has it just right.<\/p>\n ———<\/p>\n\n