Restoration of immune and renal function in aged females by re-establishment of active ovarian function

Peterson, Rhett L.; Parkinson, Kate C.; Mason, Jeffrey B.

doi:10.1071/rd16333

Cited by 11 publications

(9 citation statements)

References 37 publications

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“…Changes that positively influence inflammation are likely to positively influence many other aging pathologies. In previous work, transplantation with young ovaries positively influenced immune and renal function, reduced cardiomyopathy, decreased sarcopenia, decreased unintentional age-associated weight loss, improved cognitive behavior and sensory function, and decreased arthritis in recipient mice (Peterson et al 2017;Mason et al 2011;Peterson et al 2016;Mason et al 2010;Parkinson et al 2017;Mason et al 2015). In the current study, young ovaries transplanted to old mice produced a major reduction in the severity of inflammation, suggesting a significant ovarian influence on immune function.…”

Section: Inflammationmentioning

confidence: 78%

“…Among mice analyzed over a 4-month period, beginning at the time of reproductive senescence, inflammationassociated cytokines decreased with aging/reproductive failure, but were restored/maintained by 4 months of exposure to new, intact ovaries. T cell function was also improved in these mice and in 13-month-old mice with in situ germ cell-depleted ovaries (Peterson et al 2017;Habermehl TL, Parkinson KC, Mason JB (2018) Germ cell depletion influenced neuromuscular, sensory, renal and metabolic function in post reproductive female mice. (submitted)).…”

Section: Inflammationmentioning

confidence: 88%

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Extension of longevity and reduction of inflammation is ovarian-dependent, but germ cell-independent in post-reproductive female mice

et al. 2018

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Cardiovascular disease, rare in premenopausal women, increases sharply at menopause and is typically accompanied by chronic inflammation. Previous work in our laboratory demonstrated that replacing senescent ovaries in post-reproductive mice with young, actively cycling ovaries restored many health benefits, including decreased cardiomyopathy and restoration of immune function. Our objective here was to determine if depletion of germ cells from young transplanted ovaries would alter the ovarian-dependent extension of life and health span. Sixty-day-old germ cell-depleted and germ cell-containing ovaries were transplanted to postreproductive, 17-month-old mice. Mean life span for female CBA/J mice is approximately 644 days. Mice that received germ cell-containing ovaries lived 798 days (maximum = 815 days). Mice that received germ cell-depleted ovaries lived 880 days (maximum = 1046 days), 29% further past the time of surgery than mice that received germ cellcontaining ovaries. The severity of inflammation was reduced in all mice that received young ovaries, whether germ cell-containing or germ cell-depleted. Aging-associated inflammatory cytokine changes were reversed in post-reproductive mice by 4 months of new-ovary exposure. In summary, germ cell depletion enhanced the longevity-extending effects of the young, transplanted ovaries and, as with germ cell-containing ovaries, decreased the severity of inflammation, but did so independent of germ cells. Based on these observations, we propose that gonadal somatic cells are programed to preserve the somatic health of the organism with the intent of facilitating future germline transmission. As reproductive potential decreases or is lost, the incentive to preserve the somatic health of the organism is lost as well.

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Section: Inflammationmentioning

confidence: 78%

Section: Inflammationmentioning

confidence: 88%

Extension of longevity and reduction of inflammation is ovarian-dependent, but germ cell-independent in post-reproductive female mice

et al. 2018

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“…Transplanting the ovaries of young mice into old mice can prolong the life span of the old mice (Mason et al, 2018). Cardioprotective benefits, cognitive behavior, and immune and renal functions can be positively restored by re-establishment of active ovarian function in aged female mice (Mason et al, 2011;Parkinson et al, 2017;Peterson et al, 2017). Therefore, keeping the ovaries "young" is critical.…”

Section: Introductionmentioning

confidence: 99%

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging

et al. 2021

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The ovarian system comprises vital organs in females and is of great significance for the maintenance of reproductive potential and endocrine stability. Although complex pathogenesis undoubtedly contributes to ovarian aging, increasing attention is being paid to the extensive influence of oxidative stress. However, the role of oxidative stress in ovarian aging is yet to be fully elucidated. Exploring oxidative stress-related processes might be a promising strategy against ovarian aging. In this review, compelling evidence is shown that oxidative stress plays a role in the etiology of ovarian aging and promotes the development of other ovarian aging-related etiologies, including telomere shortening, mitochondrial dysfunction, apoptosis, and inflammation. In addition, some natural antioxidants such as quercetin, resveratrol, and curcumin have a protective role in the ovaries through multiple mechanisms. These findings raise the prospect of oxidative stress modulator-natural antioxidants as therapeutic interventions for delaying ovarian aging.

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“…This dependence on reproductive function for the maintenance of health is exemplified in surgically menopausal women and in women with premature ovarian failure, who suffer from a decline in health at a much younger age than in women with traditional menopausal timing [ 18 , 40 , 43 ]. Previous experiments by our group have demonstrated significant health and longevity benefits from manipulation of ovarian function ([ 14 , 25 – 27 , 30 , 36 – 38 , 44 ]) . In the current experiments, we evaluated aging-associated and reproduction-influenced changes in motor function, utilizing two measures of health span; tremor amplitude and grip strength.…”

Section: Introductionmentioning

confidence: 99%

Aging-associated changes in motor function are ovarian somatic tissue-dependent, but germ cell and estradiol independent in post-reproductive female mice exposed to young ovarian tissue

et al. 2022

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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.

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Restoration of immune and renal function in aged females by re-establishment of active ovarian function

Cited by 11 publications

References 37 publications

Extension of longevity and reduction of inflammation is ovarian-dependent, but germ cell-independent in post-reproductive female mice

Extension of longevity and reduction of inflammation is ovarian-dependent, but germ cell-independent in post-reproductive female mice

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging

Aging-associated changes in motor function are ovarian somatic tissue-dependent, but germ cell and estradiol independent in post-reproductive female mice exposed to young ovarian tissue

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