Dying to Know Why We Die?

First, an important disclaimer.  This is NOT a discussion of deeply religious or philosophical questions, like do we really die when our bodies give out?  I'll just note that physical aging and death is something most of us are quite ambivalent about. We acknowledge it will happen eventually, but we view it as something terrifyingly unnatural and maybe, just maybe, it can be escaped somehow -- if not physically then through some philosophical or religious mechanism. But notions like the immortality of the soul, kharmic continuation, and unembodied consciousness assimilation will be left for another time, maybe to be discussed over several pints of good beer.

My focus is more down to earth (so to speak) -- why do our bodies get old and die? Why is death inevitable?  Why, exactly do we die?  As difficult as these questions may seem, there has been some rather impressive progress in the last few decades in answering them from a scientific perspective. However, before examining the most current thinking on aging and dying that has come from the scientific study of aging processes let's consider some more informal notions that I've heard friends express, and my own pet theory of death which I acknowledge in advance as being quite preposterous.

Crackpot Theories of Aging: Fine Wine, Black Holes, Leaky Buckets and Heartbeat Banks

Unencumbered by the scientific requirements of reliable evidence, logical consistency, and demonstrated generalizability, people naturally come up with their own explanations of any phenomenon, judging them as acceptable mainly if they meet the "sounds-good-to-me" test.  Generally these explanations rely heavily on reasoning by analogy ("it's like....").  Some are more sophisticated, resting the analysis on some kernel of scientific truth and then distorting and overextending the principles to make unwarranted assertions.  Naturally, I favor the second, pseudo-scientific type.

An example of the "It's like...." category is the Fine Wine Theory.  Aging is like producing fine wine -- at first the wine is young, strong, and rather too sharp and unruly on the tongue, but then as it ages through natural chemical processes it becomes better and better, developing complexity, sophistication and substance.  However, after a certain point all wine goes bad, and the chemical processes finally lead to its destruction, leaving only foul-tasting vinegar. I suspect geezers from California favor this explanation because it can justify a "drink-the-wine-while-there's-still-time" lifestyle.

A sub-category of the analogy type of theory are those that are based on the idea that life is determined by some sort of finite resource that is slowly depleted until it's gone.  The Leaky Bucket Theory is an example, and the name says it all -- we're born with full buckets of vital essence but they have holes that slowly drain the life force until...well, you know. The Heartbeat Bank is a variation on this that years ago a friend suggested to me.  His idea was that we're each born with a certain number of heartbeats to our "account"  and when they're used up our accounts are closed, along with the lid to our casket.  This idea has great appeal to couch potatoes who can argue that they are simply being frugal with their heartbeats. To them athletes are squandering their allotment and will probably die an early death.  Notice how unencumbered this one is with the mountain of evidence that has now accumulated indicating just the opposite is true -- exercise lengthens life and shortens morbidity (see my earlier blog, "How To Compress Your Morbidity").

My own pet theory is an example of the pseudo-scientific category of lay theories.  These generally sound authoritative but if examined closely they are empirically unsupported and in my case, logically absurd.  My theory is that we are each born with an accompanying teensy black hole that follows us throughout our lifetimes, getting bigger and more powerful with each passing day.  Being tuned to our personal electromagnetic auras it begins to entrap our belongings, our bodies, our energy, and finally our entire life force, though things can temporarily escape back into our realm until the final total crossing of the event horizon. Note that this theory satisfactorily explains the common geezer experience of objects blinking in and out of existence. You know, those car keys, cell phone, t.v. remote, hat, tool, false teeth, etc. that suddenly disappear -- only to reappear some time later in the exact same spot you had looked ten times.  What else could it be??

Serious and Scientific Theories of Aging and Death

Needless to say, my Black Hole theory didn't entirely satisfy my desire for an authoritative explanation of aging and death.  In my search for something more intellectually and scientifically substantive, the best source of up-to-date, readable, and thorough information that I found is presented by the American Federation for Aging Research (AFAR) and in particular their InfoAging Guide on Theories of Aging, published in 2011.  I highly recommend it.  Another excellent source is a 2010 special issue of the journal Aging and Disease, in particular the introduction by Kulin Jin.

The AFAR guide makes the distinction between theories of why we age, which are generally broad and overarching explanations, and more specific hypotheses about how we age, which are proposals about the particular mechanisms and processes of aging.  Theories about why we age tend to be mutually exclusive and contradictory, suggesting that not all of them can be true, whereas particular hypotheses about mechanisms of aging do not necessarily conflict and a number of these might be simultaneously correct.

Research regarding hypotheses of aging mechanisms has yielded a great deal of substantive knowledge on ways to slow aging and even prevent certain destructive processes altogether.  The following hypotheses have received at least some empirical support and consequently enough media coverage that they may be familiar:

• Free Radicals Bad, Anti-Oxidants Good.  Free radicals are destructive by-products of normal cellular activity and when we are young our bodies produce substances called anti-oxidants which repair most of the damage caused by free-radicals.  With age more damage accumulates, however, eventually destroying cells altogether.  Diet fads for increasing our intake of anti-oxidants were based on early research that suggested food high in these substances increased the longevity of laboratory animals.  Unfortunately more recent experiments "...have not yeilded conclusive results..." and experiments "...attempting to reverse the effects of oxidative damage by feeding experimental animals dietary antioxidants...have not yielded conclusive results" (AFAR -- see also Guide to Oxidative Damage and Aging).  Still, high-anti-oxidant foods include chocolate and red wine, so why not cover your bases, right?
• Your DNA dipstick is getting shorter and shorter. Called by scientists the Replicative Senescence Hypothesis, the idea here is that with each cell division, the protective caps on chromosomes, called telomeres, get shorter and shorter until the cell can no longer divide.  It isn't dead, but can no longer contribute to renewing the organ of which it is a part.  Although an important factor in aging, the telomere hypothesis has shortcomings as an overall theory because not all cells divide (e.g, neurons and heart muscle), and not all organisms have cells that replicate enough to produce senescence. 
• Starve yourself into immortality. Called the Caloric Restriction Hypothesis, the idea is that by reducing excess calories burned, less oxidation damage occurs. The operative word here is "excess" because experimental findings indicate that caloric restriction in which laboratory animals are maintained on balanced diets with 30-40% fewer calories doesn't change metabolic rate, but reliably increases their life span and "...retards almost all of the age-related changes mice normally undergo, including the onset of age-related diseases" (AFAR).  There's just one teensy little problem: "Rodents maintained on calorically restricted diets are thin, cold, stunted, and sometimes sterile. It is likely that such animals, although they survive to a ripe old age in the laboratory, would never stand a chance in the wild."  This makes immortality a lot less attractive to me, thank you.
• It's all in your genes: There has been encouraging research showing that altering certain genes of organisms can increase longevity.  For example, genetic alterations that reduce the amount of the growth hormone IGF-1 can extend the lives of mice, and alteration of one specific gene in the roundworm species, C. elegans, can significantly extend its lifespan. It is tempting to interpret this as evidence that aging is a programmed process that differs in timing from individual to individual because of variations in genetic expression and that genetic alteration holds the key to successfully extending our lives.  However, it's not so simple or rosy a picture as it seems.  Those genetically altered mice live a long time but are sterile and inactive, and the long-lived roundworms exhibit defects such as "...reduced ability to enter a protective dauer stage (a developmental state in which worm larvae can better survive harsh conditions), delayed development, and impaired reproduction" (AFAR). Finally, a recent Stanford University study in which the genomes of very long-lived humans were mapped failed to find any "longevity gene" that set them apart. According to one of the scientists who conducted the study, Stuart Kim, this means the genetic effect on aging "must be complex."

Note that many of these findings have a common element -- interventions that seem to prolong life do so at a cost to the organism's overall health and in particular to its reproductive ability. This means that its genes have less likelihood of being passed on compared to those of healthier yet shorter-lived individuals -- natural selection seems to have favored cellular processes that lead to declining health in older individuals and thereby to finite lifetimes.  According to AFAR, "...it is likely that tinkering with genes to improve late-life fitness could have a detrimental effect on health at younger ages." And as long as the detrimental effects do not prevent reproductive success, they could be passed on to future generations -- definitely a bad thing.

The most widely accepted overall theory of why we age and die is based on these principles of adaptation and selection.  Called the Evolutionary Senescence Theory of aging, the central premise is that "...Natural selection, because it operates via reproduction, can have little effect on later life. In the wild, predation and accidents guarantee that there are always more younger individuals reproducing than older ones. Genes and mutations that have harmful effects but appear only after reproduction is over do not affect reproductive success and therefore can be passed on to future generations"  (AFAR).  Not only that, evidence now indicates that certain genetic traits may have positive effects when we are young but are actually harmful in later years.  An example is gene p53, a gene that directs damaged cells to stop reproducing or die. This helps prevent cancerous growths in younger people, but may contribute to aging and death by impairing the body’s ability to renew deteriorating tissues as we get old..

The Evolutionary Senescence Theory is supported by considerable research and although it continues to be tested and refined, it remains the best explanation for why all organisms age and die. It also makes clear the care with which we should approach genetic modifications intended to make us live longer. 

Geezerhood, Ho!