Altered cellular metabolism and intracellular and intercellular signaling with advancing age result in widespread changes in endocrine function. Several mechanisms interact in most systems to bring about the observed changes. Aging is associated with anatomic changes of the endocrine glands. In addition, with age, changes in hormone replacement secretion occur, including alterations in circadian or seasonal biorhythms, changes in pulsatile frequency or amplitude of growth hormone secretion, as well as absolute changes in mean serum hormonal levels. The three main hormone systems that show decline with age are the gonadal hormones (menopause and andropause), the adrenal steroids DHEA and DHEA-S (adrenopause), and the GH/IGF-1 axis (somatopause).
Other changes occur in the cellular responses of target organs. Receptor binding and intracellular signaling reflect age-related alterations in plasma membrane properties, enzyme activities, and calcium mobilization. Gene expression, including translation efficiency, transcription rates, and DNA methylation, may show marked variations with age. Finally, changes in hormone clearance rates and binding to transport daily proteins contribute to the overall widespread changes observed.
The mode and mechanism of change vary with the hormone studied. In addition to intrinsic age-related changes in endocrine response, age-associated diseases, increased use of medications, changes in nutritional status, physical activity, and body composition also contribute to age-related endocrine dysfunction.
