Theories of Biological Aging

The other major group of theories postulates that genetically programmed changes that occur with increasing age are responsible for the deleterious changes that accompany aging. It is well known that development is genetically programmed, so logic dictates that aging changes might also be programmed. The principal systems implicated in this group of theories are the endocrine and immune systems. It has been easy to demonstrate that the immune system changes with age. The major function of the immune system is to recognize foreign biological entities (antigens) and destroy or inactivate them either by tagging them with very specific antibodies or by directly killing them. To do this, mammals produce circulating cells called lymphocytes in either the thymus (T-lymphocytes) or the bone marrow (B-lymphocytes). However, the thymus gradually disappears and is essentially gone by young adulthood. Thus, further production of T-lymphocytes depends upon cell proliferation and expansion of the existing pool of T-lymphocytes. The lymphocyte pool always consists of naive T-lymphocytes, which are not yet responsive to a specific antigen, and memory T-lymphocytes, which are programmed to respond to a particular antigen. As age increases, memory T-lymphocytes comprise an increasing percent of the T-lymphocyte pool, and the remaining T-lymphocytes are less able to respond to an immunologic challenge such as a bacterial infection.

The immune system is also able to distinguish between foreign antigens and nonforeign antigens. The immune system’s response to nonforeign antigens is called autoimmunity, and the frequency of autoimmune interactions increases with age. In fact, a number of age-related diseases are thought to be due to these inappropriate autoimmune responses; thus these apparently programmed changes could be important factors in aging.

It is also known that the levels of circulating hormones may change with age. This is particularly true for growth hormones, dehydroepiandrosterone (DHEA), and melatonin. It is not known whether the decreases observed are developmentally programmed to benefit the organism in some way, or whether they are simply another example of dysregulation with increasing age. A much clearer example is provided by estrogen. Estrogen declines rapidly after menopause in women, and menopause is programmed to occur at about age fifty. Besides the loss of reproductive capability, this decline in estrogen production greatly increases the risk of age-related diseases such as osteoporosis and cardiovascular disease. Thus, late-life programmed changes may produce a variety of effects, many of which are not beneficial.