NAD+ Repletion Rescues Female Fertility during Reproductive Aging
| Autor: | Ewa M. Goldys, Hayden Homer, Toshiyuki Araki, Jayanthi Maniam, Yiqing Zhao, Laurin Lau, Abbas Habibalahi, David G. Le Couteur, Saabah B. Mahbub, Lindsay E. Wu, A. Stefanie Mikolaizak, Margaret J. Morris, Dale M. Goss, Chris O'Neill, Dave R. Listijono, Kirsty A Walters, Xing L. Jin, Maria B. Marinova, Wei-Guo Nicholas Loh, Sonia Bustamante, David A. Sinclair, Jared M. Campbell, Lynn-Jee Kim, Rachael M. Wu, Nigel Turner, Angelique H. Riepsamen, Ashley S.A. Wong, Neil A. Youngson, Robert B. Gilchrist, Michael J. Bertoldo, Kaisa Selesniemi, Catherine Li, Wing-Hong Jonathan Ho, Dulama Richani |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Aging medicine.medical_treatment Mice Transgenic Nicotinamide adenine dinucleotide SIRT2 Article General Biochemistry Genetics and Molecular Biology Cofactor Andrology Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals lcsh:QH301-705.5 Nicotinamide mononucleotide In vitro fertilisation biology Embryo NAD Oocyte 3. Good health Fertility 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) chemistry biology.protein Female NAD+ kinase 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 30, Iss 6, Pp 1670-1681.e7 (2020) Cell reports |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2020.01.058 |
| Popis: | SUMMARY Reproductive aging in female mammals is an irreversible process associated with declining oocyte quality, which is the rate-limiting factor to fertility. 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. Graphical Abstract In Brief Declining oocyte quality is considered an irreversible feature of aging and is rate limiting for human fertility. Bertoldo et al. show that reversing an age-dependent decline in NAD(P)H restores oocyte quality, embryo development, and functional fertility in aged mice. These findings may be relevant to reproductive medicine. |
| Databáze: | OpenAIRE |
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