The relationship between testosterone and molecular markers of inflammation in older men.
Aging is accompanied by a pro-inflammatory state expressed by the increasing levels of inflammatory cytokines, including interleukin-6 (IL- 6), tumor necrosis factor alpha (TNF-alpha) and interleukin- 1beta (IL-1beta). At the same time, aging is associated with a decrease in serum testosterone (T) levels. There is evidence from many experimental studies that IL-6, TNF-alpha and IL-1beta inhibit T secretion by their influence on the central (hypothalamic-pituitary) and peripheral (testicular) components of the gonadal axis. On the other hand, observational and interventional studies suggest that T supplementation reduces inflammatory markers in both young and old hypogonadal men. Preliminary data from 473 older male participants of the InCHIANTI population showed a significant inverse relationship between T and soluble IL-6 receptor (sIL-6r) levels (a soluble portion of the IL-6 receptor that may enhance the biological activity of IL-6) but not with other markers of inflammation. This study, together with previous observations, suggests that a close relationship exists between the development of a pro-inflammatory state and the decline in T levels, two trends that are often observed in aging men. In the context of this paradigm, we discuss androgen deprivation therapy, a treatment used in men with metastatic prostate cancer as an ideal model to improve our understanding of the relationship between T and inflammatory markers. We advocate the notion that changes in inflammatory markers and T in aging men are causally linked. However, longitudinal and interventional studies are needed to confirm that T can be used therapeutically, based on its anti-inflammatory properties.
Maggio
M
M
Longitudinal Studies Section, Clinical Research Branch, CRB, National Institute on Aging, NIA, USA.
Basaria
S
S
Ceda
G P
GP
Ble
A
A
Ling
S M
SM
Bandinelli
S
S
Valenti
G
G
Ferrucci
L
L
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D051379:Mice; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D015415:Biomarkers; D016207:Cytokines; D013739:Testosterone