Aging

Human life span, or longevity, has two components: mean longevity (also called life expectancy) and maximum longevity. Mean longevity is the aver­age age at death of all members of a population. Throughout history, hu­man life expectancy has increased. For example, life expectancy in the United States in the late eighteenth century was thirty-five years. By the last quar­ter of the twentieth century, it had increased to seventy-two years. The sec­ond component of life span, maximum longevity, is the age at which the most long-lived individuals of a population will die. This is difficult to determine in humans but is generally accepted to fall between 110 and 120 years.

The trend for life expectancy to get closer to maximum longevity has been attributed to improvements in nutrition, sanitation, and medical care. Maximum longevity, in actuality, appears to be independent of these envi­ronmental factors and is an absolute limit, probably determined by the ac­tion of genes. The genes that determine maximum longevity are believed to be responsible for repairing errors in the genetic information, repairing mistakes in the process of protein synthesis, and determining the time of death.

Improvements in nutrition, sanitation, and medical care have contributed to increased life expectancy.

Aging Changes that Occur in Humans

Some of the most easily observed age-related changes in humans are found in the skin and its derivatives. These include a loss of pigment in the hair, wrinkling of the skin, an increase in pigment in the skin, and thickening of the nails. Other observable changes are a decrease in size, due to loss of muscle and bone mass; a decrease in muscle strength; a decrease in mobil­ity in the joints; and a variety of neurological changes, including diminished sensory function (vision, hearing, smell, and taste), increased response time, and diminished capacity for learning and memory. The latter have been at­tributed to a loss in brain mass, due at least in part to a loss of brain cells.

Less easily observed changes include a decrease in metabolic rate; di­minished function of the kidneys, lungs, and pancreas; cardiovascular dis­ease; diminished immune function; increased susceptibility to cancer; and a decrease (in males) or termination (in females) of reproductive function. All of these changes have been attributed to cellular events and processes that are described by various theories of aging.

Theories of Aging

It is widely accepted that the process of aging cannot be traced to a single cause. A number of theories have been proposed to explain the changes ob­served during aging. In order to be a valid candidate for an explanation of the aging process, the changes proposed by the theory must meet the fol­lowing criteria: (1) they will commonly occur in all or most humans; (2) as an individual ages, these changes will become more pronounced; and (3) the changes will lead to cellular or organ dysfunction that ultimately cause fail­ure of the organ or system. The following explanations are the most com­monly accepted ones for the aging process.

Free Radicals. Free radicals are chemical particles that contain an un­paired electron and are extremely reactive. They are produced by aerobic metabolism and by radiation and other environmental agents. Their effects are widespread. They alter or break down the structure of many other mol­ecules in the cell and thus impair their functions. Free radicals react with proteins, which have enzymatic, structural, and control functions. They cause breaks in deoxyribonucleic acid (DNA) and thus alter the information necessary for synthesizing proteins. They cause lipids to stick together, which causes cell membranes to break down.

Their effects on carbohydrates are less well documented. Free radicals are most abundant in the cellular organelles called mitochondria, where oxidative reactions occur. Mitochondrial damage, including damage to mi­tochondrial DNA, has been proposed as a contributing factor to the aging process. The effects of free radicals are diminished by certain enzymes (su­peroxide dismutase and catalase) that interrupt the cycle of reactions that cause their damage. Antioxidants such as vitamins C and E also protect against free radical damage by quenching the reactions.

Crosslinkage of Proteins. In addition to the effects of free radicals, pro­teins can be altered by the spontaneous and uncontrolled joining of protein molecules to one another by glucose. The cumulative effect of this glycosylation is to cause the proteins to stick together. For example, the fibrous extracellular protein collagen, found in connective tissue, becomes stiff via this process, which contributes to the wrinkling of the skin and the loss of joint mobility.

Events Affecting the Genetic Material. Mutations, or changes in the DNA, are common and can lead to changes in the structure and function of proteins. There are a number of mechanisms that can repair these changes, but it is possible that these mechanisms diminish in their effec­tiveness with age, since they are carried out by enzymatic proteins, which are themselves damaged by the aging process. Another suggestion is that there are specific genes responsible for the death of individual cells.

Also, it is known that cells in tissue culture will undergo only a certain number of cell divisions. In human cells, this limit is approximately fifty cell divisions. This so-called Hayflick limit (after the scientist who first described it) has been tentatively explained by the progressive shortening of the telom­ere, the section of each DNA molecule that is responsible for initiating repli­cation of DNA. As the telomere becomes too short, an increasing number of mistakes occur in the replicated DNA.

The Effects of Hormones. These chemical messengers normally have well- regulated effects on body tissues. Abnormally high levels of some hormones (which may be caused by other changes described here) can change the sen­sitivity of tissues to the hormones, as well as stimulate the secretion of other hormones whose uncontrolled effects could be deleterious. Insulin, growth hormone, glucocorticoid hormones, and reproductive hormones have been suggested as candidates in this mechanism.

Changes in the Immune System. This major defense system of the body may experience two kinds of change, either one of which could contribute to the aging process. First, the immune system may gradually lose its abil­ity to distinguish cells of the body from foreign cells, resulting in immune attack on the body itself. Second, the immune system appears to be less able to respond to microbes or foreign molecules, thus rendering the cells of the body more susceptible to the effects of these noxious agents. See also Autoimmune Disease; Life Cycle, Human; Mitochondrion; Peroxi­somes.

References:

Christiansen, James L., and John M. Grzybowski. Biology of Aging: An Introduction to the Biomedical Aspects of Aging . New York: McGraw-Hill, 1999.

Clark, William R. A Means to an End: The Biological Basis of Aging and Death. New York: Oxford University Press, 1999.

DiGiovanna, Augustine Gaspar. Human Aging: Biological Perspectives, 2nd ed. Boston: McGraw-Hill, 2000.

Spence, Alexander P. Biology of Human Aging, 2nd ed. Englewood Cliffs, NJ: Pren­tice Hall, 1995.