Hormonal Change and Longevity

Americans live longer lives in better health than ever. Almost any aging health care professional will tell you, however, that in the end, it’s endocrinology—or hormonal change—that leads the charge toward decline. A review in the online version of Gerontology makes it eminently clear that age-related morbidities often follow hormone-regulated homeostasis changes in later life. Endocrine deficiencies are not easily reversed in later life, and this review highlights conditions the endocrinologist is likely to see. It also argues that using locally targeted strategies to modulate dysregulated hormonal signaling during aging may have therapeutic benefit.

Hormone secretion decreases within most axes at a time when tissue sensitivity is falling and normal circadian rhythms are losing their influence. This triple threat reduces bone, skin and skeletal muscle mass and strength. It also disrupts insulin signaling, increases adipose tissue and changes immune function.

The authors review the hypothalamic-pituitary-gonadal axis and its decline beginning in the fourth decade of life. Hormonal supplementation in women has generated a good deal of controversy. In men, however, testosterone is more insidious and less defined in terms of its effects. Increases in osteoporosis, heart disease and cancer may be related to this axis.

The hypothalamic-pituitary-adrenal axis—an adaptive regulator of stress response—regulates the adrenal steroids DHEA and DHEA-S. Both of these have been targeted as anti-aging hormones. DHEA secretion peaks in life’s second decade and falls thereafter by 2—3% each year.

The hypothalamic-pituitary-thyroid axis also begins to fail, causing high rates of overt thyroid under- or over-activity in the elderly. This paper reviews both, covering their causes and long-term impact.

The remainder of the paper discusses hormones in other systems including the gut. The authors indicate that the conventional endocrine maxim of ‘block or replace’ is too simple when age-related morbidity starts and accelerates. They look to mechanisms that will control pre-receptor hormone metabolism in the future to increase longevity.