Estradiol-independent restoration of T-cell function in post-reproductive females

Aging leads to a general decline in protective immunity. The most common age-associated effects are in seen T-cell mediated immune function. Adult mice whose immune systems show only moderate changes in T-cell subsets tend to live longer than age-matched siblings that display extensive T-cell subset aging. Importantly, at the time of reproductive decline, the increase in disease risks in women significantly outpace those of men. In female mice, there is a significant decline in central and peripheral naïve T-cell subsets at the time of reproductive failure. Available evidence indicates that this naïve T-cell decline is sensitive to ovarian function and can be reversed in post-reproductive females by transplantation of young ovaries. The restoration of naïve T-cell subsets due to ovarian transplantation was impressive compared with post-reproductive control mice, but represented only a partial recovery of what was lost from 6 months of age. Apparently, the influence of ovarian function on immune function may be an indirect effect, likely moderated by other physiological functions. Estradiol is significantly reduced in post-reproductive females, but was not increased in post-reproductive females that received new ovaries, suggesting an estradiol-independent, but ovarian-dependent influence on immune function. Further evidence for an estradiol-independent influence includes the restoration of immune function through the transplantation of young ovaries depleted of follicles and through the injection of isolated ovarian somatic cells into the senescent ovaries of old mice. While the restoration of naïve T-cell populations represents only a small part of the immune system, the ability to reverse this important functional parameter independent of estradiol may hold promise for the improvement of post-reproductive female immune health. Further studies of the non-reproductive influence of the ovary will be needed to elucidate the mechanisms of the relationship between the ovary and health

The Interrelationship Between Female Reproductive Aging and Survival

The link between survival and reproductive function is demonstrated across many species and is under both long-term evolutionary pressures and short-term environmental pressures. Loss of reproductive function is common in mammals and is strongly correlated with increased rates of disease in both males and females. However, the reproduction-associated change in disease rates is more abrupt and more severe in women, who benefit from a significant health advantage over men until the age of menopause. Young women with early ovarian failure also suffer from increased disease risks, further supporting the role of ovarian function in female health. Contemporary experiments where the influence of young ovarian tissue has been restored in postreproductive-aged females with surgical manipulation were found to increase survival significantly. In these experiments, young, intact ovaries were used to replace the aged ovaries of females that had already reached reproductive cessation. As has been seen previously in primitive species, when the young mammalian ovaries were depleted of germ cells prior to transplantation to the postreproductive female, survival was increased even further than with germ cell-containing young ovaries. Thus, extending reproductive potential significantly increases survival and appears to be germ cell and ovarian hormone-independent. The current review will discuss historical and contemporary observations and theories that support the link between reproduction and survival and provide hope for future clinical applications to decrease menopause-associated increases in disease risks

Aging-Associated Changes in Motor Function Are Ovarian Somatic Tissue-Dependent, but Berm Cell and Estradiol Independent in Post-Reproductive Female Mice Exposed to Young Ovarian Tissue

A critical mediator of evolution is natural selection, which operates by the divergent reproductive success of individuals and results in conformity of an organism with its environment. Reproductive function has evolved to support germline transmission. In mammalian ovaries, this requires healthy, active gonad function, and follicle development. However, healthy follicles do not contribute to germline transmission in a dead animal. Therefore, support of the health and survival of the organism, in addition to fertility, must be considered as an integral part of reproductive function. Reproductive and chronological aging both impose a burden on health and increase disease rates. Tremors are a common movement disorder and are often correlated with increasing age. Muscle quality is diminished with age and these declines are gender-specific and are influenced by menopause. In the current experiments, we evaluated aging-associated and reproduction-influenced changes in motor function, utilizing changes in tremor amplitude and grip strength. Tremor amplitude was increased with aging in normal female mice. This increase in tremor amplitude was prevented in aged female mice that received ovarian tissue transplants, both in mice that received germ cell-containing or germ cell-depleted ovarian tissue. Grip strength was decreased with aging in normal female mice. This decrease in grip strength was prevented in aged female mice that received either germ cell-containing or germ cell-depleted tissue transplants. As expected, estradiol levels decreased with aging in normal female mice. Estradiol levels did not change with exposure to young ovarian tissues/cells. Surprisingly, estradiol levels were not increased in aged females that received ovaries from actively cycling, young donors. Overall, tremor amplitude and grip strength were negatively influenced by aging and positively influenced by exposure to young ovarian tissues/cells in aged female mice, and this positive influence was independent of ovarian germ cells and estradiol levels. These findings provide a strong incentive for further investigation of the influence of ovarian somatic tissue on health. In addition, changes in tremor amplitude may serve as an additional marker of biological age