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NAD + Repletion Rescues Female Fertility during Reproductive Aging
Cell Rep. 2020 Feb 11;30(6):1670-1681.e7. doi: 10.1016/j.celrep.2020.01.058.
Michael J Bertoldo 1, Dave R Listijono 1, Wing-Hong Jonathan Ho 1, Angelique H Riepsamen 2, Dale M Goss 3, Dulama Richani 2, Xing L Jin 4, Saabah Mahbub 5, Jared M Campbell 5, Abbas Habibalahi 5, Wei-Guo Nicholas Loh 2, Neil A Youngson 3, Jayanthi Maniam 3, Ashley S A Wong 3, Kaisa Selesniemi 6, Sonia Bustamante 7, Catherine Li 3, Yiqing Zhao 2, Maria B Marinova 2, Lynn-Jee Kim 3, Laurin Lau 2, Rachael M Wu 8, A Stefanie Mikolaizak 9, Toshiyuki Araki 10, David G Le Couteur 11, Nigel Turner 3, Margaret J Morris 3, Kirsty A Walters 2, Ewa Goldys 5, Christopher O'Neill 4, Robert B Gilchrist 2, David A Sinclair 12, Hayden A Homer 13, Lindsay E Wu 14
Abstract:
...Here, we show that this loss of oocyte quality with age accompanies declining levels of the prominent metabolic cofactor nicotinamide adenine dinucleotide (NAD+). Treatment with the NAD+ metabolic precursor nicotinamide mononucleotide (NMN) rejuvenates oocyte quality in aged animals, leading to restoration in fertility, and this can be recapitulated by transgenic overexpression of the NAD+-dependent deacylase SIRT2, though deletion of this enzyme does not impair oocyte quality. These benefits of NMN extend to the developing embryo, where supplementation reverses the adverse effect of maternal age on developmental milestones. These findings suggest that late-life restoration of NAD+ levels represents an opportunity to rescue female reproductive function in mammals.
PMID: 32049001
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063679/