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Cell Rep. 2018 Oct 16;25(3):663-676.e6. doi: 10.1016/j.celrep.2018.09.065.

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans.

Author information

1
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
2
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
3
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
4
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA.
5
Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
6
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Einstein-Mount Sinai Diabetes Research Center, Stable Isotope and Metabolomics Core Facility, Albert Einstein College of Medicine, Bronx, New York, USA.
7
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
8
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
9
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
10
Charles Perkins Centre, The University of Sydney, NSW 2006, Australia; Central Clinical School, The University of Sydney, NSW 2006, Australia; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Clinical and Experimental Sciences, Brescia University Medical School, Brescia, Italy.
11
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
12
Department of Pathology, University of Washington, Seattle, WA, USA; Department of Biology, University of Washington, Seattle, WA, USA.
13
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: derek.huffman@einstein.yu.edu.

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.

KEYWORDS:

GNMT; aging; amino acids; autophagy; dietary restriction; glycerophospholipids; glycine; metabolomics; methionine; sarcosine

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