From the Chicago Meetings
The biology of aging,☆☆,

Presented at the Seventy-third Annual Meeting of the Central Society for Clinical Research, September 21 through 23, 2000, Chicago, IL.
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What is aging?

Aging has been defined concisely by Miller1 as “a process that converts healthy adults into frail ones, with diminished reserves in most physiological systems and an exponentially increasing vulnerability to most diseases and to death.”

This definition incorporates several important concepts regarding physiologic aging. First, aging deals with the changes that take place between middle age and old age, as opposed to the physiologic changes that take place early in life during maturation. Second,

How do we age?

The biologic theories of how we age can be divided into two major categories—the “programmed”2 and “wear-and-tear”3 theories (Table I).The first category looks at aging as the result of genetic events. The programmed theories view aging as the result of an innate genetic program. This program determines the rate of aging and maximal lifespan. This view predicts the existence of a primary clock (or clocks) that times the aging process.4 In support of this, when rodent lifespan is extended by

The “programmed” theories of aging

There is much evidence that aging has a strong genetic component (Table II).

. Evidence supporting the “program” theory

• The lifespan of a given species is relatively fixed.
• Human aging has a significant genetic component.
• Single mutations in human beings can produce premature aging syndromes.
• Altered expression of a single gene may increase maximal lifespan in lower organisms.
Maximal lifespan varies widely among species, but within species it is relatively fixed. However, within a given

The “wear and tear” theories of aging

There is strong experimental evidence that wear and tear play an important role in the aging process (Table III).The production of free radicals and free radical damage increases with age.13 Longer-lived species are less susceptible to oxidative stress than shorter-lived species. Fruit flies genetically engineered to have high antioxidant defenses live longer.14 The concept that random damage to important cellular components could account for what we call “the aging process” has been around for

A unified theory of aging

Any unified theory of aging has to account for as many of the observations of “how” we age as possible. At the present time, the general form of the free radical theory does this the best. In addition, the genetic component of the aging process must be accounted for.21 Fig 1 presents a possible unified theory. The body continually undergoes oxidative damage from free radicals generated by cellular metabolism and by environmental sources. However, the body also contains elaborate mechanisms to

Why we age: An evolutionary perspective

Until now, we have been discussing the question of how we age—that is, what are the biologic mechanisms by which we develop an increasing vulnerability to diseases and death? We now turn to the question of why we age. This question can be answered from a biologic perspective in terms of evolutionary considerations. However, it should be noted that evolution works to maximize the fitness of individuals. It does not increase fitness at the species level. Therefore it does not maximize the fitness

Why we age: A philosophic perspective

As noted in the introduction, one can also address the question of why we age from a philosophic/spiritual perspective. With regard to human aging, it is amazing that we now enjoy a long period of time between the cessation of reproduction and the end of life. In women, reproduction ends at about age 50, but the average age of death is in the early 80s. As lifespan continues to increase as a result of medical advances, this post-reproductive period will continue to grow longer. The question may

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    Supported by the St Louis Geriatric Research, Education and Clinical Center; by the Medical Research Service of the Department of Veterans Affairs; and by National Institutes of Health Grant AG-12587.

    ☆☆

    Reprint requests: H. J. Armbrecht, PhD, Geriatric Center (11G-JB), St Louis VA Medical Center, St Louis, MO 63125.

    J Lab Clin Med 2001;138:220-5.

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