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

Ryan O Walters; Esperanza Arias; Antonio Diaz; Emmanuel S Burgos; Fangxia Guan; Simoni Tiano; Kai Mao; Cara L Green; Yungping Qiu; Hardik Shah; Donghai Wang; Adam D Hudgins; Tahmineh Tabrizian; Valeria Tosti; David Shechter; Luigi Fontana; Irwin J Kurland; Nir Barzilai; Ana Maria Cuervo; Daniel E L Promislow; Derek M Huffman

doi:10.1016/j.celrep.2018.09.065

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

Ryan O Walters, Esperanza Arias, Antonio Diaz, Emmanuel S Burgos, Fangxia Guan, Simoni Tiano, Kai Mao, Cara L Green, Yungping Qiu, Hardik Shah, Donghai Wang, Adam D Hudgins, Tahmineh Tabrizian, Valeria Tosti, David Shechter, Luigi Fontana, Irwin J Kurland, Nir Barzilai, Ana Maria Cuervo, Daniel E L PromislowDerek M Huffman

Department for Health

Research output: Contribution to journal › Article › peer-review

65 Citations (SciVal)

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.

Original language	English
Pages (from-to)	663-676.e6
Journal	Cell Reports
Volume	25
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2018.09.065
Publication status	Published - 16 Oct 2018

Keywords

Adult
Aged
Aging/physiology
Animals
Biomarkers/analysis
Caloric Restriction
Cohort Studies
Female
Homeostasis
Humans
Longevity
Male
Metabolome
Mice
Middle Aged
Rats
Rats, Inbred BN
Rats, Inbred F344
Sarcosine/blood

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10.1016/j.celrep.2018.09.065Licence: CC BY-NC-ND

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Walters, R. O., Arias, E., Diaz, A., Burgos, E. S., Guan, F., Tiano, S., Mao, K., Green, C. L., Qiu, Y., Shah, H., Wang, D., Hudgins, A. D., Tabrizian, T., Tosti, V., Shechter, D., Fontana, L., Kurland, I. J., Barzilai, N., Cuervo, A. M., ... Huffman, D. M. (2018). Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans. Cell Reports, 25(3), 663-676.e6. https://doi.org/10.1016/j.celrep.2018.09.065

Walters, RO, Arias, E, Diaz, A, Burgos, ES, Guan, F, Tiano, S, Mao, K, Green, CL, Qiu, Y, Shah, H, Wang, D, Hudgins, AD, Tabrizian, T, Tosti, V, Shechter, D, Fontana, L, Kurland, IJ, Barzilai, N, Cuervo, AM, Promislow, DEL & Huffman, DM 2018, 'Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans', Cell Reports, vol. 25, no. 3, pp. 663-676.e6. https://doi.org/10.1016/j.celrep.2018.09.065

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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.",

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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\}",

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AU - Burgos, Emmanuel S

AU - Guan, Fangxia

AU - Tiano, Simoni

AU - Mao, Kai

AU - Green, Cara L

AU - Qiu, Yungping

AU - Shah, Hardik

AU - Wang, Donghai

AU - Hudgins, Adam D

AU - Tabrizian, Tahmineh

AU - Tosti, Valeria

AU - Shechter, David

AU - Fontana, Luigi

AU - Kurland, Irwin J

AU - Barzilai, Nir

AU - Cuervo, Ana Maria

AU - Promislow, Daniel E L

AU - Huffman, Derek M

PY - 2018/10/16

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N2 - 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.

AB - 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.

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KW - Aged

KW - Aging/physiology

KW - Animals

KW - Biomarkers/analysis

KW - Caloric Restriction

KW - Cohort Studies

KW - Female

KW - Homeostasis

KW - Humans

KW - Longevity

KW - Male

KW - Metabolome

KW - Mice

KW - Middle Aged

KW - Rats

KW - Rats, Inbred BN

KW - Rats, Inbred F344

KW - Sarcosine/blood

U2 - 10.1016/j.celrep.2018.09.065

DO - 10.1016/j.celrep.2018.09.065

M3 - Article

C2 - 30332646

SN - 2211-1247

VL - 25

SP - 663-676.e6

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -

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

Abstract

Keywords

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