Home / Articles / Hormones / Testosterone, Ageing, and Alzheimer's

Testosterone, Ageing, and Alzheimer's

By Dr. John M Berardi, Ph.D.
First published at www.mothernature.com, 2001.

Printer friendly version

As of late, an abundance of research has shown that testosterone levels decline dramatically in aged men. This decline in testosterone has been linked health problems such as loss of muscle and bone mass, increased fat mass, sexual dysfunction, and depression to name a few. With these changes in mind, many forward thinking researchers have investigated the effects of testosterone replacement in aging males with positive results. One startling new finding is that not only can testosterone improve the above conditions but it appears that testosterone may also have an impact on Alzheimer's disease!

Beta-amyloid protein, the main protein linked with the disease, is secreted as the brain's neurons age. Some experts believe that as beta-amyloid accumulates it tangles up with the existing nerve cells and strangles them. All that is left after beta-amyloid comes are bundles of dead nerve cells and the smooth pathways of nerve transmission in the brain are destroyed.

One particular study showed that testosterone can reduce the secretion of beta-amyloid protein in the cerebral cortex. This offers protection against nerve cell destruction. The researchers involved in this study concluded that "These results raise the possibility that testosterone supplementation in elderly men may be protective in the treatment of Alzheimer's disease."

Since there is research to indicate that physically active older men can maintain both higher levels of testosterone and growth hormone than age matched sedentary men, it appears that exercise can help in the prevention of age associated testosterone decline. This would have a positive impact on many of the diseases of aging, potentially even alzheimers.

Fit Tip: Resistance and cardiovascular training can help preserve muscle and bone mass, sexual function, and testosterone levels and may even ward of some of the diseases of aging. In addition, although unproven for such purposes, some older men have even combined testosterone boosters and prohormones with exercise in an attempt to maintain "healthy" testosterone levels and the associated benefits.

Hurel SJ, et al. Relationship of physical exercise and ageing to growth hormone production. Clin Endocrinol (Oxf) 1999 Dec;51(6):687-91.

Gouras GK, et al. Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides. Proc Natl Acad Sci U S A 2000 Feb 1;97(3):1202-5

Relationship of physical exercise and ageing to growth hormone production.

Clin Endocrinol (Oxf) 1999 Dec;51(6):687-91

Hurel SJ, Koppiker N, Newkirk J, Close PR, Miller M, Mardell R, Wood PJ, Kendall-Taylor P

Department of Endocrinology, Medical School, Newcastle-upon-Tyne, UK.

OBJECTIVE: The normal decline in physiological function with ageing is associated with a decrease in bioavailable growth hormone. Growth hormone has been shown to alter body composition and increase fat-free mass in older men. Increased physical fitness is accompanied by an increase in 24-h growth hormone release. The purpose of this study was to examine the effect of exercise on declining growth hormone concentrations with increasing age. DESIGN AND PATIENTS: The growth hormone production of 10 male subjects running over 40 miles per week was compared to 10 healthy age-matched sedentary males (controls 57.7 +/- 2.8 vs. runners 60.5 +/- 3.4 years). All subjects underwent a basal assessment including a two-hour serum growth hormone profile followed by estimation of maximal exercise capacity on a cycle ergometer with growth hormone estimations at peak exercise activity and every five minutes whilst cycling at 40% of maximal exercise capacity. RESULTS: Maximal exercise capacity confirmed the lifestyles of the two groups (VO2 max controls 22.36 +/-6.05 vs. runners 34.91 +/- 13.13 l/min/kg, P = 0.01). The runners had lower body-mass indices than controls (BMI 22. 3 +/- 1.5 vs. 25.5 +/- 2.0 kg/m2, P = 0.002). Peak growth hormone level during a two-hour resting profile was higher in the runners (median (range) controls 2.10 (0.20-12.20) vs. runners 5.25 (0.80-21. 00) mU/l, P = 0.03) as was the average growth hormone level during the two hour profile (mean growth hormone per 2 h median (range): controls 0.54 (0.03-4.88) vs. runners 2.17 (0.25-7.45) mU/l, P = 0. 04). Growth hormone production at maximal exercise capacity was similar. Sex hormone binding globulin and testosterone were significantly higher in the runners. CONCLUSIONS: The results suggest that regular intensive exercise in older male subjects is associated with higher growth hormone and testosterone levels and that exercise may have a role in counteracting the normal decline in growth hormone with ageing.

Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides.

Proc Natl Acad Sci U S A 2000 Feb 1;97(3):1202-5

Gouras GK, Xu H, Gross RS, Greenfield JP, Hai B, Wang R, Greengard P

Laboratory of Molecular and Cellular Neuroscience and Fisher Center for Research on Alzheimer's Disease, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

Alzheimer's disease (AD) is characterized by the age-related deposition of beta-amyloid (Abeta) 40/42 peptide aggregates in vulnerable brain regions. Multiple levels of evidence implicate a central role for Abeta in the pathophysiology of AD. Abeta peptides are generated by the regulated cleavage of an approximately 700-aa Abeta precursor protein (betaAPP). Full-length betaAPP can undergo proteolytic cleavage either within the Abeta domain to generate secreted sbetaAPPalpha or at the N- and C-terminal domain(s) of Abeta to generate amyloidogenic Abeta peptides. Several epidemiological studies have reported that estrogen replacement therapy protects against the development of AD in postmenopausal women. We previously reported that treating cultured neurons with 17beta-estradiol reduced the secretion of Abeta40/42 peptides, suggesting that estrogen replacement therapy may protect women against the development of AD by regulating betaAPP metabolism. Increasing evidence indicates that testosterone, especially bioavailable testosterone, decreases with age in older men and in postmenopausal women. We report here that treatment with testosterone increases the secretion of the nonamyloidogenic APP fragment, sbetaAPPalpha, and decreases the secretion of Abeta peptides from N2a cells and rat primary cerebrocortical neurons. These results raise the possibility that testosterone supplementation in elderly men may be protective in the treatment of AD.

PMID: 10655508, UI: 20122595