The Pacemaker Theory of Aging
The genetic theory of aging

The pacemaker theory of aging is based on the notion of "biological clocks," systems or processes that are set at birth to run for a specified period of time and then wind down, leading to aging and death. The two bodily systems most often suggested as the clocks or pacemakers are the neuroendocrine system and the immune system.

The neuroendocrine system refers to the complex connections between the brain and nervous system and our endocrine glands. The hypothalamus, a structure at the base of the brain, stimulates and inhibits the pituitary gland, often called the "master gland," which in turn regulates the glands of the body (ovaries, testes, adrenal glands, thyroid) and how and when they release their hormones into our circulation. As we age, this system becomes less functional, and this can lead to high blood pressure, impaired sugar metabolism, and sleep abnormalities. The actions that the various hormones our different glands produce on different facets of aging have been studied extensively. The most obvious example of age-related hormone changes, and aging as a result of hormone changes, is menopause.

An interesting experiment has been done that argues strongly in favor of a neuroendocrine pacemaker effect of aging. Laboratory mice underwent surgical removal of their pituitary glands. Researchers then replaced all the known hormones under the control of the pituitary. The hormone-treated mice had a longer life span than healthy mice that had retained their native pituitary glands and secreted their own hormones. Some, though certainly not all, researchers are persuaded by these findings that the pituitary must secrete at least one additional hormone, either a death or aging hormone whose secretion increases as we age, or a protective "Methuselah" hormone, whose secretion decreases with age. Neither of these, however, has yet been identified.

Like hormones, the levels of the key immune cells of the immune system also decline as we age. White blood cells called T-cells and to a lesser degree B-cells, both decline in number and function. The thymus, a structure active in the production of T-cells, begins to involute, or shrink, in adolescence. All this evidence points to an immune system clock. Professor Fabris of Italy agues, however, that the involution of the thymus is the result of, and not the cause of aging. He notes that inducing the thymus to reconstitute itself can bring about improved immunity among the elderly.¹⁴

Researchers supporting the immune system as the aging pacemaker also point to the known increase in cancers that occurs with age. Many potential cancers that would have been held in check by a youthful and functional immune system avoid destruction as we age, and our immune systems lose potency.

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Proponents of the genetic theory of aging believe that life span is determined by the genes we inherit.¹⁵ Aging is seen as beginning at birth or even at conception. Some of the evidence cited in support of the genetic theory of aging is the fact that life expectancy is consistent across members of a species, and the fact that females tend to live longer than males (and this is observed among most other animal species, not only among humans). Among humans, evidence of the genetic contribution to aging and life span includes the observation that long-lived parents tend to have long-lived children, that some families have been identified that have exceptionally high numbers of centenarians and nonagenarians, and the fact that identical twins have much more closely related life expectancies than other siblings do.

The genes that affect aging can be either helpful, promoting longevity, or deleterious, shortening life span. The helpful genes are often called longevity assurance genes. These particular genes usually come in several different versions, most of which are not especially helpful, and may indeed be life-shortening, but one of which is associated with a longer than average life span. Such helpful genes include one version of a gene for a protein called apolipoprotein E as well as certain versions of genes for immune proteins.¹⁶

Another aspect of the genetic influence on aging can be seen by looking at our mitochondria, the energy powerhouses of our cells. Mitochondrial gene mutations can result in the loss of the ability to generate energy. Mitochondria with genetic mutations may also leak the molecule cytochrome c, which can ultimately lead to cell death. Finally, mutations can occur in mitochondrial genes that are associated with Parkinson's and Alzheimer's diseases, both related to aging.¹⁷

Even the strongest proponents of the genetic theory of aging acknowledge that external influences can affect our genes. Genes can be modified or damaged by free radicals,¹⁸ toxins, ultraviolet light and radiation. Recognizing the interplay between our genes and the external conditions to which we subject them should lead to a deeper understanding of the process of aging.

Today, most experts in the biology of the aging process believe that a combination of genetic and stochastic events is responsible for aging. Any single limited theory of aging is certain to be insufficient.

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