Healthy aging is associated with unaltered production of immunoreactive growth hormone but impaired neuroimmunomodulation.

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 vitro by 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.

Psychoneurodendocrine correlates of lymphocyte subsets during healthy ageing.

Ageing has been associated with increased cortisol levels and absolute counts of T lymphocytes with memory phenotype. Although the mechanisms underlying these changes are still unknown, it has been speculated that this could be related to a dysfunction in FAS/CD95 expression in naive or memory cells. In this study, we investigated the role of psychoneuroendocrine variables in regulating CD95 expression on lymphocyte subsets. Forty-six elderly subjects (65-91 years) and 33 young adults (20-40 years) were recruited accordingly the SENIEUR protocol. The psychological status was measured by structured clinical interviews, salivary cortisol was assessed along the day (9, 12 and 22h) and peripheral blood lymphocytes were immunophenotyped. The elderly were more stressed, depressed and anxious than the young subjects. Cortisol levels were increased in the elderly, indicating an activation of the hypothalamic-pituitary-adrenal (HPA) axis. We observed reduced counts of CD45RA+CD95+ cells in the elderly compared to young adults. The elderly subjects also showed a reduced expression of CD3 and CD62L in contrast to increased CD95 expression in CD45RA+ cells. The emotional state was positively correlated with the lymphocyte markers. Our data suggest the healthy ageing is associated with psychoneuroendocrine alterations that may be implicated in the regulation of CD95 expression on peripheral T cells.

Impact of psychological and endocrine factors on cytokine production of healthy elderly people.

Human ageing has been associated with immunological changes including blunted T-cell responses and increased production of pro-inflammatory cytokines. Here, we investigated the role of psychological and endocrine factors in the production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin (IL)-6) as well as soluble IL-2Ralpha, associated with T-cell activation. Forty-six elderly subjects (60-91 yrs) and 33 young adults (20-40 yrs) were recruited accordingly the SENIEUR protocol. The emotional status was measured by structured clinical interviews. Salivary cortisol levels (9, 12 and 22 h) and serum dehydroepiandrosterone (DHEA) were assessed by radioimmunoassays. The elderly were more stressed, depressed and anxious than the young subjects. Cortisol levels were increased whereas DHEA levels were significantly reduced in the elderly. Both groups showed equivalent production of pro-inflammatory cytokines as well as soluble IL-2Ralpha. Psychological scores were positively correlated to evening cortisol levels and negatively correlated to morning DHEA levels. No relationships were noted between psychological factors and cytokines studied. However, evening cortisol levels were found positively correlated to TNF-alpha and sIL-2Ralpha levels. These data indicate that healthy ageing is associated with significant distress and activation of the hypothalamic-pituitary-adrenal axis. Our data also suggest that there are complex psychoneuroendocrine relationships involved with cytokine production during ageing.