. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011 Sep 1;477(7362):90-4. PubMed.


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  1. This paper supports the reproductive-cell cycle theory of aging, which indicates that reproductive endocrine dyscrasia mediates aging in all tissues via altered cell cycle signaling (Bowen and Atwood, 2004; Atwood and Bowen, 2011). The blood-borne factors inducing brain aging may, in fact, be due to elevated concentrations of circulating gonadotropins and GnRH, and decreased concentrations of sex steroids and inhibin, in the aged post-reproductive mouse. This work is further supported by the finding that transplantation of young ovaries (two-month-old) into middle-aged (11-month-old) mice significantly increased longevity by re-establishing the hypothalamic-pituitary-gonadal axis. These data indicate that reproductive hormones are primarily responsible for aging. Supporting this, the major cytokines correlated with aging in the 2011 paper by Villeda et al.—CCL2, haptoglobulin, and eotaxin (CCL11)—are regulated by (Bouckaert et al., 1986; Dahm-Kähler et al., 2006), or correlated with (Kass et al., 2010) LH and FSH concentrations.


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