@article{e7cf1e2d210447fc851be7764bd58098,
title = "Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans",
abstract = "A hallmark of aging is a decline in metabolic homeostasis, which is attenuated by dietary restriction (DR). However, the interaction of aging and DR with the metabolome is not well understood. We report that DR is a stronger modulator of the rat metabolome than age in plasma and tissues. A comparative metabolomic screen in rodents and humans identified circulating sarcosine as being similarly reduced with aging and increased by DR, while sarcosine is also elevated in long-lived Ames dwarf mice. Pathway analysis in aged sarcosine-replete rats identify this biogenic amine as an integral node in the metabolome network. Finally, we show that sarcosine can activate autophagy in cultured cells and enhances autophagic flux in vivo, suggesting a potential role in autophagy induction by DR. Thus, these data identify circulating sarcosine as a biomarker of aging and DR in mammalians and may contribute to age-related alterations in the metabolome and in proteostasis. In a comparative metabolic screen of rodents and humans, Walters et al. show that circulating sarcosine is similarly reduced with aging and increased by dietary restriction. They demonstrate that sarcosine activates macroautophagy in cultured cells and in vivo, suggesting a role in improved proteostasis via dietary restriction.",
keywords = "GNMT, aging, amino acids, autophagy, dietary restriction, glycerophospholipids, glycine, metabolomics, methionine, sarcosine",
author = "Walters, {Ryan O.} and Esperanza Arias and Antonio Diaz and Burgos, {Emmanuel S.} and Fangxia Guan and Simoni Tiano and Kai Mao and Green, {Cara L.} and Yungping Qiu and Hardik Shah and Donghai Wang and Hudgins, {Adam D.} and Tahmineh Tabrizian and Valeria Tosti and David Shechter and Luigi Fontana and Kurland, {Irwin J.} and Nir Barzilai and Cuervo, {Ana Maria} and Promislow, {Daniel E.L.} and Huffman, {Derek M.}",
note = "Funding Information: This work has been supported by the National Institute on Aging (NIA) ( R00AG037574 and R56AG052981 ) and the American Federation for Aging Research (AFAR) to D.M.H.; the Einstein Nathan Shock Center for Excellence in the Biology of Aging P30AG038072 and R37AG18381 to N.B.; P01AG031782 to A.M.C.; and R01GM108646 to D.S. D.E.L.P. received support from NIA grants R01AG049494 and R01AG013280 . R.O.W. and T.T. are supported by a T32 Training Grant ( T32AG23475 ) and A.D.H. is supported by T32GM007491 . E.A. received support from the NIH/NIA P30AG038072 Pilot & Feasibility (P&F) Award and the NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DK041296 P&F Award. This work was also supported by the Einstein-Sinai Diabetes Research Center ( P30DK020541 ) and the National Cancer Institute (NCI)-supported Einstein Cancer Center ( P30CA013330 ). The authors would like to acknowledge the Northwest Metabolomics Research Center and the valuable assistance of Lisa F. Bettcher, Dr. Robert Pepin, and Dr. Daniel Raftery in performing metabolomic data analysis. The authors would finally like to thank Dr. Pasha Apontes, Hongqian Liang, and Zunju Hu for technical assistance. Funding Information: This work has been supported by the National Institute on Aging (NIA) (R00AG037574 and R56AG052981) and the American Federation for Aging Research (AFAR) to D.M.H.; the Einstein Nathan Shock Center for Excellence in the Biology of Aging P30AG038072 and R37AG18381 to N.B.; P01AG031782 to A.M.C.; and R01GM108646 to D.S. D.E.L.P. received support from NIA grants R01AG049494 and R01AG013280. R.O.W. and T.T. are supported by a T32 Training Grant (T32AG23475) and A.D.H. is supported by T32GM007491. E.A. received support from the NIH/NIA P30AG038072 Pilot & Feasibility (P&F) Award and the NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DK041296 P&F Award. This work was also supported by the Einstein-Sinai Diabetes Research Center (P30DK020541) and the National Cancer Institute (NCI)-supported Einstein Cancer Center (P30CA013330). The authors would like to acknowledge the Northwest Metabolomics Research Center and the valuable assistance of Lisa F. Bettcher, Dr. Robert Pepin, and Dr. Daniel Raftery in performing metabolomic data analysis. The authors would finally like to thank Dr. Pasha Apontes, Hongqian Liang, and Zunju Hu for technical assistance. Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2018",
month = oct,
day = "16",
doi = "10.1016/j.celrep.2018.09.065",
language = "English",
volume = "25",
pages = "663--676.e6",
journal = "Cell Reports",
issn = "2211-1247",
number = "3",
}