Dietary restriction mitigates the age-associated decline in mouse B cell receptor repertoire diversity.

Aging impairs the capacity to respond to novel antigens, reducing immune protection against pathogens and vaccine efficacy. Dietary restriction (DR) extends life- and health span in diverse animals. However, little is known about the capacity of DR to combat the decline in immune function. Here, we study the changes in B cell receptor (BCR) repertoire during aging in DR and control mice. By sequencing the variable region of the BCR heavy chain in the spleen, we show that DR preserves diversity and attenuates the increase in clonal expansions throughout aging. Remarkably, mice starting DR in mid-life have repertoire diversity and clonal expansion rates indistinguishable from chronic DR mice. In contrast, in the intestine, these traits are unaffected by either age or DR. Reduced within-individual B cell repertoire diversity and increased clonal expansions are correlated with higher morbidity, suggesting a potential contribution of B cell repertoire dynamics to health during aging.

Androgens in Menopausal Women: Not Only Polycystic Ovary Syndrome.

Menopause is the period of a woman's life that is characterized by the permanent cessation of menses associated to hormonal changes, of which the most important is the decrease of estrogen levels. Following menopause, the concentrations of circulating androgens decrease. However, increased concentrations of luteinizing hormone induce androgens secretion from the ovaries and presumably from the adrenal glands. Peripheral conversion of androgens results to the circulating hormonal androgen profile. Some pathological conditions are associated with greater concentrations of androgens after menopause than in controls, with polycystic ovary syndrome (PCOS) being the commonest. These conditions can be distinguished in non-tumorous (adrenal or ovarian) or functional and tumorous (adrenal or ovarian benign or malignant) masses. Apart from PCOS, other non-tumorous (adrenal or ovarian) causes of hyperandrogenism in post-menopausal women are obesity, non-classic congenital adrenal hyperplasia (NCCAH), endocrinopathies, such as Cushing disease or acromegaly; ovarian hyperthecosis, drug use or abuse. Tumorous (adrenal or ovarian) causes include adrenal cortical cancers, adrenal benign adenomas and even incidentalomas, or ovarian tumors such as the sex-cord stromal ovarian tumors and metastases in the ovary. The diagnosis of hyperandrogenism is made through medical history, clinical examination, and laboratory tests. Total testosterone concentration of 150 ng/dL can be used at first to distinguish a malignant from a benign cause of hyperandrogenism. Dehydroepiandrosterone sulfate concentration may support adrenal source of androgens. Imaging techniques are used to localize the source of androgens: computed tomography and magnetic resonance imaging (MRI) for the adrenals and transvaginal ultrasound or MRI for the ovaries. Finally, treatment (etiologic and symptomatic) and long-term effects of hyperandrogenism are developed in this chapter.

A nutritional memory effect counteracts benefits of dietary restriction in old mice.

Dietary restriction (DR) during adulthood can greatly extend lifespan and improve metabolic health in diverse species. However, whether DR in mammals is still effective when applied for the first time at old age remains elusive. Here, we report results of a late-life DR switch experiment employing 800 mice, in which 24 months old female mice were switched from ad libitum (AL) to DR or vice versa. Strikingly, the switch from DR-to-AL acutely increases mortality, whereas the switch from AL-to-DR causes only a weak and gradual increase in survival, suggesting a memory of earlier nutrition. RNA-seq profiling in liver, brown (BAT) and white adipose tissue (WAT) demonstrate a largely refractory transcriptional and metabolic response to DR after AL feeding in fat tissue, particularly in WAT, and a proinflammatory signature in aged preadipocytes, which is prevented by chronic DR feeding. Our results provide evidence for a nutritional memory as a limiting factor for DR-induced longevity and metabolic remodeling of WAT in mammals.