Endocrine System

Among the most intellectually compelling theories of aging are those based on the notion that selection pressure favors those mechanisms which increase the probability of reproductive success (i.e., of producing a next generation of viable offspring). This relationship would be true even if, for example, the mechanisms utilized early in life to assure reproductive success ultimately contribute to senescence and reduce the longevity of postreproductive-age adults (Rose). The dual and apparently contradictory nature of this particular proposal is reflected in the term used to describe it, "antagonistic pleiotropy." Similar to antagonistic pleiotropy is another hypothesis called the "disposable soma." According to this view, the soma (body) is principally a vehicle for reproduction that becomes disposable once reproductive success has been achieved. In practice, this means that the resources of the body are targeted to assuring the perpetuation of the species instead of being distributed in a manner that may also help increase life span (Kirkwood).

Reproduction, including the antecedent development of reproductive organs and secondary sexual characteristics, is under strong hormonal control. If aging and life span are linked to the cessation of reproductive activity, as proposed above, then it follows that hormones likely play an important role in these events. In humans the most prominent sex hormones are the steroids estrogen (estradiol), progesterone, and testosterone. Of these, estrogen has probably received the greatest attention as a putative regulator of the aging process. Estrogen availability and levels determine the occurrence of two landmark events in the life cycle of women, menarche and menopause, and its virtual disappearance in postmenopausal women is associated with a variety of disorders and regressive tissue changes Figure 1 An illustration showing the human endocrine system. SOURCE: Argosy, Inc. for the Gale Group commonly associated with aging (Perry). These associations include the loss of bone (osteoporosis) and changes in skin texture, and the increased risk of cataracts, cardiovascular disease, and dementia. In addition, because of the reciprocal relationship between hormone levels and, for example, bone loss, estrogen has been used extensively in hormone replacement therapy (HRT), the goal being to counteract the negative effects of postmenopausal estrogen deficiency, that is, those changes commonly associated with aging (Palacios). Thus, by this criterion, estrogen is an antiaging hormone.

While estrogen is almost certainly the most widely recognized sex hormone that likely plays a role in aging, it is not the only sex hormone that has this distinction. There are two others that also have gained significant attention. One of these is testosterone, which was recognized many years ago, albeit indirectly, as an agent (factor) important in maintaining the vigor and general vitality of older males. This association had its origins in nineteenth-century research involving testicular transplants in animals (the goal being to restore the sexual activity of valuable old, stud animals), and progressed to the use of both transplants and testicular extracts in middle-aged to elderly human males (Gosden). This early work gave results that were at best equivocal, but it did establish the basis for research on hormone isolation and characterization, and the rationale for the use of testosterone in HRT. Testosterone levels in men do decline with age (the phenomenon is called andropause), and low levels of the hormone have been equated with the loss of libido and cognitive skills, physical frailty, and bone loss. Testosterone HRT is an accepted form of therapy, particularly for men who are clearly hypogonadal (defined as bioavailable testosterone below the reference range for young men), but its widespread use remains controversial because of side effects (Bain).

The other sex steroid that has been widely implicated in the aging process is dehydroepiandrosterone (DHEA). DHEA is a weak androgen, produced by the adrenal gland, that can act directly on target tissues or indirectly as a precursor molecule for both estrogen and testosterone. DHEA, and its sulfated derivative DHEA-S, reach peak levels in young adults and decline steadily thereafter in most individuals. The blood levels at age eighty-five are, on average, about 10 percent of that in young adults. This diminution in DHEA/DHEA-S is called adrenopause. Lower levels of the hormone have been associated with age-related changes in body composition, the frequency of some forms of cancer, type II diabetes, atherosclerosis, and ischemic heart disease (Hinson and Raven). As is the case with estrogen and testosterone, DHEA has been and is being used in HRT, frequently in uncontrolled circumstances by the public at large in the United States. Although data from animal studies indicate that DHEA supplementation can counter some age-related changes (e.g., in immune function), the results on healthy, older humans leave the question of benefit in doubt (Svec and Porter). However, DHEA may be of help in some medical conditions, including serum lupus erythematosis and serious depression. No adverse effects have been reported.

No discussion of hormones and aging would be complete without consideration of human growth hormone (HGH) and insulin-like growth factor-1 (IGF-1). HGH is produced by the pituitary and affects target tissues principally through a mediating hormone/cytokine, IGF-1, that is synthesized in peripheral tissue. HGH and IGF-1 are potent anabolic agents capable of stimulating cell proliferation and protein synthesis, and recombinant HGH is the intervention of choice for treating individuals with short stature and adult HGH deficiency. HGH and IGF-1 levels decline with age (somatopause) (Vermeulen), and HGH and HGH secretagogue therapy have emerged as strategies for helping the frail elderly regain strength and muscle mass. However, as is the case with testosterone, it remains to be seen whether the benefits of such an approach outweigh the risks to the individuals, including peripheral edema and a decrease in insulin sensitivity (Cummings and Merriam). Ironically, recent data show that dwarf mice with growth hormone deficiency and, as a consequence, reduced body size live longer than their normal littermates.