NAD + Repletion Rescues Female Fertility during Reproductive Aging.

Autor:	Bertoldo MJ; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Listijono DR; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Ho WJ; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Riepsamen AH; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Goss DM; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia., Richani D; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Jin XL; Human Reproduction Unit, Kolling Institute, Sydney Medical School, University of Sydney, St Leonards, NSW, Australia., Mahbub S; ARC Centre of Excellence in Nanoscale Biophotonics, UNSW Sydney, NSW, Australia., Campbell JM; ARC Centre of Excellence in Nanoscale Biophotonics, UNSW Sydney, NSW, Australia., Habibalahi A; ARC Centre of Excellence in Nanoscale Biophotonics, UNSW Sydney, NSW, Australia., Loh WN; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Youngson NA; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia., Maniam J; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia., Wong ASA; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia., Selesniemi K; Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston MA, USA; Jumpstart Fertility Pty Ltd., Sydney, NSW, Australia., Bustamante S; Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, UNSW Sydney, Sydney, NSW, Australia., Li C; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia., Zhao Y; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Marinova MB; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Kim LJ; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia., Lau L; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Wu RM; Graduate Entry Medical School, University of Limerick, Limerick, Republic of Ireland., Mikolaizak AS; Neuroscience Research Australia, Randwick, NSW, Australia., Araki T; Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan., Le Couteur DG; ANZAC Medical Research Institute, University of Sydney, Concord, NSW, Australia., Turner N; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia., Morris MJ; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia., Walters KA; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Goldys E; ARC Centre of Excellence in Nanoscale Biophotonics, UNSW Sydney, NSW, Australia., O'Neill C; Human Reproduction Unit, Kolling Institute, Sydney Medical School, University of Sydney, St Leonards, NSW, Australia., Gilchrist RB; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia., Sinclair DA; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia; Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston MA, USA. Electronic address: david_sinclair@hms.harvard.edu., Homer HA; School of Women's and Children's Health, UNSW Sydney, Sydney, NSW, Australia; Christopher Chen Oocyte Biology Laboratory, University of Queensland Centre for Clinical Research, Royal Brisbane & Women's Hospital, Herston, QLD, Australia. Electronic address: h.homer@uq.edu.au., Wu LE; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia. Electronic address: lindsay.wu@unsw.edu.au.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Feb 11; Vol. 30 (6), pp. 1670-1681.e7.
DOI:	10.1016/j.celrep.2020.01.058
Abstrakt:	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. Competing Interests: Declaration of Interests L.E.W., H.A.H., and D.A.S. are cofounders, shareholders, directors, and advisers of Jumpstart Fertility Inc., which was founded to develop the work described here, and are inventors on a patent (WO2019023748A1 “Methods to improve fertility”) that forms the basis of this work and has been licensed to Jumpstart Fertility. D.A.S. is an inventor on a patent (WO2013002880A1) that was previously licensed to Jumpstart Fertility. The salaries of M.J.B. and D.M.G. working in the labs of L.E.W. and R.B.G. at UNSW were paid by sponsored research from Jumpstart Fertility to UNSW. K.S. was an employee of Jumpstart Fertility. W.-H.J.H. and D.R.L. hold shares in Jumpstart Fertility. H.A.H. undertakes ART in the private sector in affiliation with Queensland Fertility Group. L.E.W. and D.A.S. are also advisers and shareholders in EdenRoc Sciences (Metro Biotech NSW, Metro Biotech, Liberty Biosecurity) and in Life Biosciences LLC and its daughter companies (Jumpstart Fertility, Continuum Biosciences, Senolytic Therapeutics, Selphagy, Animal Biosciences, Iduna). L.E.W. provides consulting work for Life Biosciences and is an adviser and shareholder in Intravital Pty Ltd. D.A.S. is also a founder, equity owner, adviser, director, consultant, investor, and/or inventor on patents licensed to Vium, Jupiter Orphan Therapeutics, Cohbar, Galilei Biosciences, Wellomics, EdenRoc Sciences (and affiliates Arc-Bio, Dovetail Genomics, Claret, Revere Biosciences, UpRNA, MetroBiotech, Liberty Biosecurity), Life Biosciences (and affiliates Selphagy, Senolytic Therapeutics, Spotlight Therapeutics, Animal Biosciences, Iduna, Continuum, Jumpstart Fertility, Iduna). D.A.S. is an inventor on a patent application filed by Mayo Clinic and Harvard Medical School that has been licensed to Elysium Health. For details see https://genetics.med.harvard.edu/sinclair. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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