Authors: 
S.M. Harman
Category: 
Invited
Conference: 
Abstract: 

Aging changes in body composition and metabolism bear a striking resemblance to those seen in states of male and female sex hormone, thyroid, and growth hormone (GH) deficiencies and cortisol excess. This resemblance, plus observed decreases with age in testosterone in men, estrogen in women, and GH in both sexes have led some to conclude that aging is caused by hormonal alterations and to the use of hormone replacement as anti-aging therapy. However, this strategy results in, at best, partial reversal of changes in lean and fat body mass, bone density, metabolism, and function, and begs the question as to what changes in cell biochemistry underlie alterations in hormone secretion and action and what processes lead to such changes. We propose that cumulative free radical damage and crosslink formation in differentiated cells leads to loss of cell membrane fluidity, causing impaired signal transduction, and, hence, failure of secretory cells to respond appropriately to regulatory factors and of target cells to respond optimally to hormone stimulation. The resulting dysregulation is manifest by alterations in circulating hormone levels, but also as failure of muscle, bone, fat, etc. to respond fully to exogenous hormones. Age-related loss of membrane fluidity and impaired signal transduction have been demonstrated in animal studies as has their restoration by treatments which improve membrane fluidity or replace senescent cells with new cells having freshly synthesized cell membrane components. The applicability of this model to human aging remains to be demonstrated.

Keywords (Optional): 
hormones
membrane fluidity
signal transduction