Cropped screen shot from Annie Hall. Fair use. United Artists
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In a scene in the 1977 movie “Annie Hall,” Tony Roberts climbs into his convertible with Woody Allen and carefully zips up the body and hood of his protective suit. “Keeps out the alpha rays,” he says to Allen, “You don’t get old.”
Aging is a complex, physiological phenomenon (that is not, as far as we know, caused by alpha rays). Every cell, every tissue and every organ of the body are changed in the aging process. There are two lines of questioning that we could follow concerning aging and life span (“life span” being a nice way of saying “dying”): the first asks “why?” Why do all organisms age and why do they die? And the second asks “how?” How do organism’s age and how does death come about?
“Why” questions are often very difficult to answer scientifically, but aging and death are probably most clearly explained via reference to evolution and, maybe, the purpose of life itself. Richard Dawkins in his book The Selfish Gene describes the purpose of life as a drive to preserve and replicate DNA (or “genes”):
“ We are survival machines—robot vehicles blindly programmed to preserve the selfish molecules known as genes.”
Figure by Radio89, Wikimedia Commons
Once replication and preservation of DNA has occurred, Life (or Nature) has little use for the parental generation. In almost all species, physiological and anatomical changes occur in post-reproductive (“senescent”) individuals that either decrease their chances of survival in their ecosystems or directly cause debilitating diseases and death. Resources need to be available for the next “replication and preservation” cohort rather than for the maintenance of the now evolutionary dead-end group. In a Natural Selection system long, post-reproductive life spans could only be selected for in situations where resources were super abundant and non-limiting, or where individuals had such a slow rate of metabolism that they used very few resources as they aged. Also, and this is the essence of “Grandmother hypothesis” in human beings, longer life spans could be selected in situations where the post-reproductive individuals contribute in some positive way to the survival of their offspring or their offspring’s offspring.
So why do organisms age and die? Mostly because their job is done, and their continued presence might harm their passed-along DNA.
Looking at the second question, how aging occurs and how death comes about, is much more satisfying path of exploration in that understanding these things may enable us to resist them! In a human-controlled world (one in which cultural values, aspirations and technologies have by and large replaced the “nature red in tooth and claw” world of Natural Selection) we see discussion of and progress toward what Yuval Noah Harari has described in his book Homo Deus: A Brief History of Tomorrow as the newest “ultimate” goal of humanity: immortality.
So, what do we know about the physiology and molecular biology of aging?
Telomere caps on chromosomes. US Dept of Energy, Human Genome Program
Each strand of your DNA in every cell of your body is marked with a curious feature of aging: the ends of your DNA strands (the “telomeres”)) get shorter each time the DNA replicates. Every time one of your cells divides, the length of the information molecules that encode the instructions for all aspects of you and is, according to Dawkins’ selfish gene theory the whole reason for your existence, erodes away. It is not known, though, if this shortening of your telomeres is one of the causes of aging or just one of its many symptoms.
It is possible to introduce or activate an enzyme (called “telomerase”) into a cell that repairs these shortening telomeres. This happens in many types of cancer, and the cancerous cells then are able to multiply indefinitely without any DNA erosion. Some tissue cultures of these cells are referred to as “immortal,” and they continue to replicate and thrive often many decades after the original cell donor has died. The big (unanswered) question about telomeres is: if telomerase were switched on in all cells of an individual would that individual’s body become an immortal assemblage of cells or would it turn into a seething mass of out-of-control cancerous tumors?
Aging Diagram. Dw001, Wikimedia Commons
Oxidative stress is unquestionably a major factor in aging. Most organisms take in oxygen to allow their cellular energy generating systems to function, but some 2 to 3% of these oxygen molecules end up being reduced by stray electrons that bleed out of the energy-generating metabolic pathways. These reduced oxygen molecules become “reactive oxygen species” (ROS) (like superoxide anions, hydrogen peroxide and hydroxyl radicals). ROS’s then attack a cell’s macromolecules (proteins, lipids, nucleic acids) and cause chronic, cumulative damage to the cell.
Studies in nematodes and fruit flies in which genes are inserted that code for intracellular synthesis of anti-oxidant enzymes or in which drugs are administered that accomplish the reduction of these molecular degrading agents do result in the expansion of life span in both types of these invertebrate organisms. Laboratory and human-clinical studies in which dietary anti-oxidants (like Vitamin C, E, beta-carotene or flavonoid anthocyanins) are administered, however, have not shown any impact on or benefit to the slowing of the aging process or the expansion of life span. It is interesting, though, that some of the oxidative-stress reducing genes that may lengthen life spans may also have deleterious effects on the pre-reproductive survival of these organisms. Recent studies on nematodes showed a greater susceptibility to bacterial infections and higher rates of early life mortality in individuals that possessed the “oxidative stress reducing” “life span enhancing” genes (Nature Communications, July 27, 2019).
Possibly related to this oxidative stress hypothesis are observations that have been made in lab animals and humans that have been kept under severe caloric restriction (CR). CR not only changes an organism’s regulation of energy metabolism but also may result in the synthesis of metabolic proteins that enhance the cell’s ability to resist both aging and also a number of degenerative processes. Longer life spans and inhibited development of Alzheimer’s and Parkinson’s diseases have all been observed in CR experiments.
Great white shark. Photo by T. Gross. Wikimedia Commons
In aging, the stability of a cell’s DNA declines. There is inhibited recognition and repair of mutated or transposed nucleotide sequences in both nuclear and mitochondrial DNA. These altered base sequences inevitably involve vital sections of the genome and the failure of important cellular systems. These changes can reduce the ability of a cell to run normal metabolism and maintain normal homeostasis or cause it to significantly degrade in function or grow out of control and become cancerous. The long life span of the great white shark (70+ years) and remarkable evolutionary stability of sharks as a group (almost 500 million years!) have been correlated to the extensive number of genes they have that participate in DNA control and repair and an equally large portion of their genome that is involved in tissue repair and healing (see Proceedings of National Academy of Sciences, February 18, 2018).
Giant tortoise. Photo by Childzy. Wikimedia Commons
Giant tortoises and parrots are two other types of organisms that have extremely long life spans. Both have been shown to have clusters of genes that control cell growth, DNA repair, and energy metabolism (see Current Biology, December 7, 2018 (parrots) and Nature, Ecology & Evolution, December 3, 2018 (giant tortoises)). The natural selection systems for these extended, post-reproductive life spans might fit two of our proposed evolutionary models: tortoises have remarkably slow rates of metabolism (and, so, will not over-exploit their ecosystem’s food resources) and parrots with their high levels of intelligence and extensive nurturing of their young, may be assisting in the survival of their progeny or their progeny’s progeny!
Anyway, much is known about lifespans and aging, but very little is known for certain. Philosophically looking at life (and death), I think the best thing is to recognize that life itself is finite and that we should enjoy every minute of it. I would also recommend the “life” advice given to the protagonist in John Irving’s novel Cider House Rules, “be of use!” All of the generations coming after us need our help!
If you would like to read more about the biological and molecular aspects of life span and aging check out these two online sources: Molecular Biology of Aging ( by Johnson, Sinclair and Guarente) and Biology of Aging National Institute on Aging (US-HHS).