Aging, Biology of
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.
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.
Steven N. Trautwein
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