Healthy Aging Is Associated with Unaltered Production of Immunoreactive Growth Hormone but Impaired Neuroimmunomodulation

Abstract

Background: Both endocrine and immune systems are continuously remodeled during aging. Objective: Here, we investigated to what extent adrenal and somatosenescence are associated reciprocal changes in the immune system during strictly healthy aging. Methods: Forty-six elderly subjects and 33 young adults were recruited according to the health criteria of the SENIEUR protocol. Peripheral blood mononuclear cells were isolated and stimulated in vitro with lipopolysaccharide or phytohemagglutinin to assess the production of immunoreactive growth hormone (GH). Peripheral sensitivity to steroids was assessed in vitroby dexamethasone-, cortisol- or dehydroepiandrosterone (DHEA)-induced inhibition of T-cell proliferation. DHEA and GH levels were measured by radioimmunoassays. Results: Healthy elderly had lower salivary DHEA and serum GH levels (somatosenescence). They presented reduced T-cell sensitivity to dexamethasone but similar cellular sensitivities to cortisol and DHEA. Their cells produced similar levels of immunoreactive GH compared to the cells of young adults. Conclusions: These data indicate that healthy aging is associated with adrenal and somatosenescence as well as impaired neuroendocrine immunoregulation at the level of the lymphocyte. In addition, somatosenescence may not be associated with a reciprocal decline in immunoreactive GH.

Neuroendocrine and Immunological Correlates of Chronic Stress in ‘Strictly Healthy’ Populations

“…All subjects were screened according to the strictly healthy criteria established by the SENIEUR protocol [16] . The health conditions were checked according to previous work [12,13] and were based on accurate clinical investigations and hematological and biochemical parameters. Forty-one (32 females) strictly healthy and primary caregivers (mean 8 SD age: 60.56 8 11.56 years) and 33 strictly healthy (26 females) and non-stressed controls (mean 8 SD age: 60.27 8 14.10 years) were included in the study.…”

“…Healthy aging has been associated with neuroendocrine and immunological changes including hypothalamic-pituitary-adrenal (HPA) axis activation with increasing cortisol [12] and blunted cell-mediated immunity [13] . The caregivers of demented patients had further reduced T cell function as well as impaired steroid immunoregulation in association with increased cortisol levels compared to nonstressed elderly controls [2,14] .…”

Chronic Stress and Immunosenescence: A Review

“…In addition, it was observed that healthy elders had lower dehydroepiandrosterone (DHEA) levels (-54%) throughout the day compared to young adults [31] . Furthermore, elders also displayed a flat circadian pattern for DHEA secretion.…”

“…Indeed, we have observed that healthy SENIEUR elders were significantly more distressed, had activated HPA axis and significantly lower (-53.6%) T cell proliferation compared to young adults ( fig. 2 ) [31] . Interestingly, the HPA axis may be implicated with this change, since salivary cortisol levels were found negatively correlated to T cell proliferation.…”

“…We have previously investigated the lymphocyte sensitivity to both synthetic (dexamethasone, DEX) and naturally occurring steroids (cortisol and DHEA) and so examined whether aging was associated with alterations in neuroendocrine immunoregulation [31] . It was found that healthy elders had a reduced (-19%) in vitro lymphocyte sensitivity to DEX (but not cortisol or DHEA) when compared to young adults.…”