Review of Medical Physiology - William F. Ganong 2002

Introduction
General Principles and Cellular Basis of Human Physiology
Aging

Aging is a universal physiological process that remains poorly understood. While many countries worldwide are experiencing an increase in average life expectancy, Ukraine, unfortunately, is not. In Ukraine, life expectancy in 1999 was 73.3 years for women and 62.9 years for men, with an overall average of 68.3 years. In the United States, life expectancy rose from 47 years in 1900 to over 75 years today. However, this increase is primarily the result of improved medical treatments, the Prevention of infections, and the control of other causes of premature death, which allows more people to surpass the 70-year threshold. In contrast, the maximum human lifespan of 100 to 110 years has remained virtually unchanged. Aging affects Cells, the systems they comprise, and tissue components such as Collagen. A wide variety of theories have been proposed to explain this phenomenon.

According to one theory of aging, Tissues deteriorate As a result of random Mutations in the DNA of somatic cells, leading to the accumulation of cellular anomalies. Another theory suggests that cumulative anomalies are driven by an increase in the cross-linking of collagen and other Proteins, possibly resulting from the non-enzymatic combination of glucose with amino groups on these molecules. Yet another theory views aging as the cumulative outcome of tissue Damage caused by free radicals. This is particularly interesting given that longer-lived species produce superoxide dismutase, an enzyme that deactivates oxygen free radicals (see Chapter 27).

Research has shown that chronically restricted caloric intake extends the lifespan of rodents. Preliminary data indicate that this may also apply to monkeys and, potentially, humans. The lifespan-extending effect of caloric restriction is presumably explained by a slowed METABOLISM, which results in reduced formation of protein cross-links and free radicals. Evidence supporting The Theory of cumulative DNA damage comes from recent findings regarding Werner syndrome—a condition characterized by premature aging—where the genetic defect stems from a mutation in the Gene encoding DNA helicase, an enzyme that unwinds DNA strands prior to Replication. This abnormality is believed to cause an extremely rapid accumulation of chromosomal damage. Furthermore, mice lacking a component of telomerase (see above) age prematurely and exhibit defects characteristic of human Werner syndrome. In addition, as human cells age, A large number of mutations accumulate in the portion of Mitochondrial DNA that controls replication. This can lead to impaired energy production or potentially increase the generation of free radicals within the cells. Nevertheless, the precise contribution of such factors to the aging process remains to be fully elucidated.

Aging in humans is accompanied by declining circulating levels of certain Sex Hormones, the adrenal androgens dehydroepiandrosterone and its sulfate, and Growth Hormone. Estrogen and progesterone replacement therapy in women (see Chapter 23) reduces the incidence of Osteoporosis and cardiovascular disease. Replacement therapies involving testosterone (see Chapter 23), dehydroepiandrosterone (see Chapter 20), and growth hormone (see Chapter 22) offer therapeutic benefits; however, they are associated with undesirable side effects, and there is little evidence that they actually prolong life.