PMID- 32028263 OWN - NLM STAT- MEDLINE DCOM- 20210122 LR - 20210122 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 12 IP - 3 DP - 2020 Feb 6 TI - Methionine increases yolk production to offset the negative effect of caloric restriction on reproduction without affecting longevity in C. elegans. PG - 2680-2697 LID - 10.18632/aging.102770 [doi] AB - Caloric restriction (CR) or Dietary restriction (DR) is known to improve health and in many cases increases lifespan. However, its negative effect on reproduction has not been fully studied. Practicing CR/DR without adequate knowledge on its side effect may risk complications such as infertility, birth defect, or malnutrition. In this study, by using several CR strategies in C. elegans, we examine key functions of reproduction including embryonic development and larvae growth. We find that CR significantly decreases the survival of embryos and slows the growth of the offspring. We further determine that defect in oocyte but not sperm is responsible for the compromised reproduction under CR. Interestingly, adding methionine to the medium reverses the reproduction defects, but does not affect the long lifespan resulted from CR. The beneficial effect of methionine on reproduction requires the yolk protein vitellogenin. CR down-regulates vitellogenin expression, which can be reversed by supplementing methionine in the food. Lacking the yolk protein transport due to rme-2 mutation blocks methionine's beneficial effects. Our study has revealed a novel, methionine-mediated genetic pathway linking nutrient sensing to reproduction and suggested methionine as a potential food supplement to mitigate the side effect of CR. FAU - Zhou, Gaojian AU - Zhou G AD - Basic Medicine College, Central South University, Changsha, Hunan, People's Republic of China. FAU - Huang, Chuan AU - Huang C AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, People's Republic of China. FAU - Xing, Liu AU - Xing L AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, People's Republic of China. FAU - Li, Le AU - Li L AD - ProMab Biotechnologies, Richmond, CA 94806, USA. FAU - Jiang, Yan AU - Jiang Y AD - Hunan Gaocell Medical Technology Co. Ltd., Changsha, Hunan, People's Republic of China. FAU - Wei, Yuehua AU - Wei Y AD - Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China. LA - eng GR - P40 OD010440/OD/NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200206 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - AE28F7PNPL (Methionine) SB - IM MH - Animals MH - Caenorhabditis elegans/*physiology MH - *Dietary Supplements MH - Egg Yolk/*metabolism MH - *Energy Intake MH - *Longevity MH - Methionine/administration & dosage/*pharmacology PMC - PMC7041781 OTO - NOTNLM OT - calorie restriction (CR) OT - methionine OT - reproduction OT - side effect OT - vitellogenin COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest. EDAT- 2020/02/07 06:00 MHDA- 2021/01/23 06:00 PMCR- 2020/02/15 CRDT- 2020/02/07 06:00 PHST- 2019/10/24 00:00 [received] PHST- 2020/01/12 00:00 [accepted] PHST- 2020/02/07 06:00 [pubmed] PHST- 2021/01/23 06:00 [medline] PHST- 2020/02/07 06:00 [entrez] PHST- 2020/02/15 00:00 [pmc-release] AID - 102770 [pii] AID - 10.18632/aging.102770 [doi] PST - ppublish SO - Aging (Albany NY). 2020 Feb 6;12(3):2680-2697. doi: 10.18632/aging.102770. Epub 2020 Feb 6.