Biochemistry of Aging

BIOCHEMISTRY OF AGING F. MAROTT SINEX, Ph.D.* Most of us consider aging an unfortunate affliction of the human race which will eventually be responsible for considerable personal inconvenience . In spite ofthe importance ofaging in our own experience and in the experiences ofthose about us, aging is well tolerated. Private foundations do not call on us to war on aging as on cancer, heart diseases, stroke, or muscular dystrophy. To think about aging and death is unsettling to the young and old alike. The elderly are more concerned about how aging affects their own personal needs, often economic, than about the fundamental nature ofthe process. In spite of the rather surprising lack of curiosity about aging on the part ofthe general public, the problem has fascinated biologists. It is possible that until quite recently scientists lacked the essential knowledge and techniques to approach the aging problem. I will attempt to summarize what is known about biological and chemical mechanisms operative during senescence. Is aging in the human species the result of deliberate biological programming closely related to the total developmental history, or are human beings about as long lived as might reasonably be expected ofan organisir. ofthis complexity and chemical stability? Is aging centered in the nucleus, in the cell as a whole, or in extracellular components such as collagen or elastin? How efficient is the process ofreplacement ofdefective molecules? I. Aging and Evolution For there to be cell death, there must be cell life. It is difficult to visualize aging in the most primitive ofliving systems, where being a living system, and ceasing to be a living system, may have presented some problems in definition. * Boston University School ofMedicine. 208 F. Marott Sinex · Biochemistry ofAging Perspectives in Biology and Medicine · Winter ic, In terms ofwhat now exists on earth, aging in many forms oflife seems rather deliberately programmedand adjustedfor thepassage ofthe seasons. Weismann [?] felt that the aging ofthe individual developed to facilitate the survival ofthe species. In a monocarpic plant it would appear advantageous that a wintering form, the seed, survive the winter in a dormant condition, protected from the elements, and in the spring not face competition from adults of the previous generation. In such a plant, removal ofthe flowers in order to prevent the setting of seed may materially prolong the life-span. In insects it is the adult form which undergoes the final senescence. Some larval forms are extremely long lived if pupation is prevented by hormonal manipulation. Moulting continues to produce larval forms so long as the juvenile hormone of the corpus aliata is produced. The cells of the larval forms then undergo a form of degeneration which may or may not be analogous to senescence. These cells are replaced by cells from embryonic rests to form the tissues ofthe adult. Insects appear particularly adaptable to nutritional programming. The worker honey bee which winters over lives four times as long a life as a summer worker [2]. Human development and senescence do not follow the seasons. We must live long enough to attain an appreciable size, physical maturity, brain development, and memory. We must protect and educate our children during their relatively slow development. Human beings are large, very long-lived mammals. To achieve such longevity the human being must function efficiently, repair injury, resist infection, and maintain the chemical integrity of a complex system ofhigh polymers and structural lipid over many years' incubation at 38o. Man may have special problems in doing so, such as the size ofhis aorta and magnitude ofhis blood pressure . We must marvel at the ability ofthe human organism to function as well as it does as long as it does. Such considerations have caused Medawar [3] and Bidder [4] to argue that in a species such as man a long period of fertility to conceive and educate the young is a definite evolutionary advantage and that the length of our senescence merely reflects that perfection and protective redundancy present in middle life. In the wild state, deaths ofmost vertebrates result from predators, from difficulties in finding food, from the elements, and from infection. Aging 209 is more characteristic ofcaptive and well-structured societies such as ours in which the...