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

Abstract

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.

Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells: a potential mechanism for the prevention of vascular cognitive impairment

“…4). Recent developments in our understanding of mechanisms of aging (Deepa et al 2017;Fang et al 2017;Grant et al 2017;Konopka et al 2017;Podlutsky et al 2017;Cunningham et al 2018;Habermehl et al 2018;Kim et al 2018;Lewis et al 2018;Masser et al 2018;Nacarelli et al 2018;Olecka et al 2018;Reglodi et al 2018) and vascular aging processes (Csiszar et al 2017;Tarantini et al 2017a, b;Tucsek et al 2017;Ungvari et al 2017a, b;Csipo et al 2018;Fulop et al 2018;Lee et al 2018;Reglodi et al 2018;Sure et al 2018;Ungvari et al 2018b, c) highlight the importance of in vitro screening assays that model complex physiological processes for the evaluation of the anti-aging effects of novel pharmacological interventions. The combination of the in vitro assays used in this study, based on rescue of age-related loss-of-function in endothelial cells, could correctly identify the anti-aging effects of caloric restriction (Csiszar et al 2013(Csiszar et al , 2014 as well as neuroendocrine factors (Banki et al 2015).…”

Chemically induced carcinogenesis in rodent models of aging: assessing organismal resilience to genotoxic stressors in geroscience research

“…In geroscience studies (Bennis 2017;Blodgett et al 2017;Contreras et al 2018;Deepa et al 2017;Fang et al 2017;Fulop et al 2018;Habermehl et al 2018;Kaeberlein 2018;LaRoche et al 2018;Lee et al 2018;Lewis et al 2018;Logan et al 2018;Meschiari et al 2017;Nacarelli et al 2018;Reglodi et al 2018;Scerbak et al 2018;Snider et al 2018;Tenk et al 2017;Tucsek et al 2017;Ungvari et al 2017;Urfer et al 2017;Vedovelli et al 2017), there is a growing need for new assays to assess organismal stress resilience, including resistance to genotoxic stresses, to predict health span and lifespan and to predict the efficiency of novel antiaging treatments. Testing DMBA-induced mammary carcinogenesis in mice is a useful assay to measure resilience to genotoxic stress.…”

Individual evaluation of luteinizing hormone in aged C57BL/6 J female mice

“…Thus, menopause in women is reported to have a negative impact on inflammation, gynecologic cancer, and cardiovascular disease (Shi et al 2016). Therefore, protocols aiming at maintaining/restoring reproductive activity (Habermehl et al 2019) may help alleviating the negative impact of reproductive senescence on health.…”