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Endocrine changes with aging

Author
S Mitchell Harman, MD, PhD
Section Editors
Kenneth E Schmader, MD
Peter J Snyder, MD
Deputy Editor
Kathryn A Martin, MD

INTRODUCTION

Since the 19th century, there have been sporadic attempts to attribute the changes of aging to one or another endocrine deficit and efforts to reverse these changes with a variety of endocrine therapies. This search for a hormonal "fountain of youth" continues today with, as an example, the widespread use of dehydroepiandrosterone (DHEA) as a "nutritional supplement." Of greater clinical significance is the increasing practice of "off-label" prescribing of human growth hormone (hGH) and potent androgenic steroids for age-related declines in GH/insulin-like growth factor-1 (IGF-1) and testosterone (T), termed respectively, "somatopause" and "andropause." The evidence for age-related changes in endocrine function and their clinical consequences are reviewed here; disease-related changes are reviewed elsewhere. (See "Overview of testosterone deficiency in older men" and "Dehydroepiandrosterone and its sulfate" and "Growth hormone deficiency in adults".)

PHYSIOLOGY OF AGING

The complexity of the aging process precludes simplistic formulations that equate aging with hormone deficiency. Biological aging is characterized by a progressive and, to a considerable extent, predictable loss of coordinated cell and tissue function, such that the organism becomes gradually less fit to reproduce and survive. The rate of this process is species specific, and changes are manifested across multiple organs and systems. Deterioration of function is heterogeneous among systems and individuals and is generally detectable first as a loss of reserve capacity and ability to restore homeostasis under stress, then later by altered function at rest.

The basic mechanisms underlying aging are unknown. The best available evidence is consistent with the accumulation of a variety of (unrepaired) biochemical alterations that impair the function of nucleic acids, proteins, and lipid membranes. These alterations probably include oxidation by free radicals [1] but also nonenzymatic glycosylation [2] and epigenetic changes such as DNA methylation and histone acetylation [3]. The extent to which differentiated cells are affected by aging determines physiologic function, while the extent to which reserve (stem and precursor) cells are affected determines the capacity to replace damaged differentiated cells and repair tissues [4]. Some studies have suggested the presence of circulating factors in aged organisms that inhibit stem cell mobilization and compromise damage repair [4,5]. However, the biochemical identities of the cytokines involved remain to be determined.

A well-described phenomenon of aging is a widely distributed deterioration of signal transduction efficiency. Examples include a reduction in the vasodilatory response of the endothelium to estrogen, possibly related to the progressive methylation of the estrogen receptor gene (an epigenetic change) [6] and reduced Leydig cell responsiveness to gonadotropin stimulation (probably due to altered cell membrane biochemistry) [7,8].

Endocrine changes — In considering changes in endocrine function in older people, it is important to distinguish between the effects of aging per se on endocrine physiology and those caused by age-related illness, given the high prevalence of disorders, both symptomatic and asymptomatic, in older adults. The distinction is simple in concept but not in practice.

                          

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