A metabolic atlas of mouse aging

Steven E. Pilley; Dominik Awad; Djakim Latumalea; Connie New; Edgar Esparza; Shuo Wang; Xuanyi Shi; Li Zhang; Maximilian Unfried; Jasinda H. Lee; Ernst Schmid; Ipsita Mohanty; Jenna L.E. Blum; Shivaanishaa Raventhiran; Esther Wong; Preeti R. Iyengar; Racheal Mulondo; Sriraksha Bharadwaj Kashyap; Darius Moaddeli; Peter Sajjakulnukit; Damien Sutton; Harrison K.A. Wong; Yaqi Gao; George Wang; Aeowynn J. Coakley; Gilberto Garcia; Ryo Higuchi-Sanabria; Anja Karlstaedt; Timothy L. Frankel; Marina Pasca di Magliano; Whitaker Cohn; Sophia Liu; Bingfei Yu; Pieter C. Dorrestein; Ernest Fraenkel; Shawn M. Davidson; William B. Tu; Brian K. Kennedy; Costas A. Lyssiotis; Peter J. Mullen

doi:10.1016/j.cmet.2025.10.016

A metabolic atlas of mouse aging

Steven E. Pilley
, Dominik Awad
, Djakim Latumalea
, Connie New
, Edgar Esparza
, Shuo Wang
, Xuanyi Shi
, Li Zhang
, Maximilian Unfried
, Jasinda H. Lee
, Ernst Schmid
, Ipsita Mohanty
, Jenna L.E. Blum
, Shivaanishaa Raventhiran
, Esther Wong
, Preeti R. Iyengar
, Racheal Mulondo
, Sriraksha Bharadwaj Kashyap
, Darius Moaddeli
, Peter Sajjakulnukit

Damien Sutton, Harrison K.A. Wong, Yaqi Gao, George Wang, Aeowynn J. Coakley, Gilberto Garcia, Ryo Higuchi-Sanabria, Anja Karlstaedt, Timothy L. Frankel, Marina Pasca di Magliano, Whitaker Cohn, Sophia Liu, Bingfei Yu, Pieter C. Dorrestein, Ernest Fraenkel, Shawn M. Davidson, William B. Tu, Brian K. Kennedy, Costas A. Lyssiotis, Peter J. Mullen

Veterinary and Biomedical Sciences

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

12 Scopus citations

Abstract

Humans are living longer and experiencing more age-related diseases, many of which involve metabolic dysregulation, but how metabolism changes in multiple organs during aging is not known. Answering this could reveal new mechanisms of aging and therapeutics. Here, we profile metabolic changes in 12 organs in male and female mice at 5 different ages. We also develop organ-specific metabolic aging clocks that identify metabolic drivers of aging, including alpha-ketoglutarate, previously shown to extend lifespan in mice. We also use the clocks to uncover that carglumic acid is a potential driver of aging and show that it is synthesized by human cells. Finally, we validate that hydroxyproline decreases with age in the human pancreas, emphasizing that our approach reveals insights across species. This study reveals fundamental insights into the aging process and identifies new therapeutic targets to maintain organ health.

Original language	English (US)
Pages (from-to)	399-418.e7
Journal	Cell Metabolism
Volume	38
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2025.10.016
State	Published - Feb 3 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2025.10.016

Cite this

Pilley, S. E., Awad, D., Latumalea, D., New, C., Esparza, E., Wang, S., Shi, X., Zhang, L., Unfried, M., Lee, J. H., Schmid, E., Mohanty, I., Blum, J. L. E., Raventhiran, S., Wong, E., Iyengar, P. R., Mulondo, R., Kashyap, S. B., Moaddeli, D., ... Mullen, P. J. (2026). A metabolic atlas of mouse aging. Cell Metabolism, 38(2), 399-418.e7. https://doi.org/10.1016/j.cmet.2025.10.016

@article{66069fb53a8e40a5b52429f2bb99117b,

title = "A metabolic atlas of mouse aging",

abstract = "Humans are living longer and experiencing more age-related diseases, many of which involve metabolic dysregulation, but how metabolism changes in multiple organs during aging is not known. Answering this could reveal new mechanisms of aging and therapeutics. Here, we profile metabolic changes in 12 organs in male and female mice at 5 different ages. We also develop organ-specific metabolic aging clocks that identify metabolic drivers of aging, including alpha-ketoglutarate, previously shown to extend lifespan in mice. We also use the clocks to uncover that carglumic acid is a potential driver of aging and show that it is synthesized by human cells. Finally, we validate that hydroxyproline decreases with age in the human pancreas, emphasizing that our approach reveals insights across species. This study reveals fundamental insights into the aging process and identifies new therapeutic targets to maintain organ health.",

author = "Pilley, \{Steven E.\} and Dominik Awad and Djakim Latumalea and Connie New and Edgar Esparza and Shuo Wang and Xuanyi Shi and Li Zhang and Maximilian Unfried and Lee, \{Jasinda H.\} and Ernst Schmid and Ipsita Mohanty and Blum, \{Jenna L.E.\} and Shivaanishaa Raventhiran and Esther Wong and Iyengar, \{Preeti R.\} and Racheal Mulondo and Kashyap, \{Sriraksha Bharadwaj\} and Darius Moaddeli and Peter Sajjakulnukit and Damien Sutton and Wong, \{Harrison K.A.\} and Yaqi Gao and George Wang and Coakley, \{Aeowynn J.\} and Gilberto Garcia and Ryo Higuchi-Sanabria and Anja Karlstaedt and Frankel, \{Timothy L.\} and \{Pasca di Magliano\}, Marina and Whitaker Cohn and Sophia Liu and Bingfei Yu and Dorrestein, \{Pieter C.\} and Ernest Fraenkel and Davidson, \{Shawn M.\} and Tu, \{William B.\} and Kennedy, \{Brian K.\} and Lyssiotis, \{Costas A.\} and Mullen, \{Peter J.\}",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier Inc.",

year = "2026",

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doi = "10.1016/j.cmet.2025.10.016",

language = "English (US)",

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pages = "399--418.e7",

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Pilley, SE, Awad, D, Latumalea, D, New, C, Esparza, E, Wang, S, Shi, X, Zhang, L, Unfried, M, Lee, JH, Schmid, E, Mohanty, I, Blum, JLE, Raventhiran, S, Wong, E, Iyengar, PR, Mulondo, R, Kashyap, SB, Moaddeli, D, Sajjakulnukit, P, Sutton, D, Wong, HKA, Gao, Y, Wang, G, Coakley, AJ, Garcia, G, Higuchi-Sanabria, R, Karlstaedt, A, Frankel, TL, Pasca di Magliano, M, Cohn, W, Liu, S, Yu, B, Dorrestein, PC, Fraenkel, E, Davidson, SM, Tu, WB, Kennedy, BK, Lyssiotis, CA & Mullen, PJ 2026, 'A metabolic atlas of mouse aging', Cell Metabolism, vol. 38, no. 2, pp. 399-418.e7. https://doi.org/10.1016/j.cmet.2025.10.016

TY - JOUR

T1 - A metabolic atlas of mouse aging

AU - Pilley, Steven E.

AU - Awad, Dominik

AU - Latumalea, Djakim

AU - New, Connie

AU - Esparza, Edgar

AU - Wang, Shuo

AU - Shi, Xuanyi

AU - Zhang, Li

AU - Unfried, Maximilian

AU - Lee, Jasinda H.

AU - Schmid, Ernst

AU - Mohanty, Ipsita

AU - Blum, Jenna L.E.

AU - Raventhiran, Shivaanishaa

AU - Wong, Esther

AU - Iyengar, Preeti R.

AU - Mulondo, Racheal

AU - Kashyap, Sriraksha Bharadwaj

AU - Moaddeli, Darius

AU - Sajjakulnukit, Peter

AU - Sutton, Damien

AU - Wong, Harrison K.A.

AU - Gao, Yaqi

AU - Wang, George

AU - Coakley, Aeowynn J.

AU - Garcia, Gilberto

AU - Higuchi-Sanabria, Ryo

AU - Karlstaedt, Anja

AU - Frankel, Timothy L.

AU - Pasca di Magliano, Marina

AU - Cohn, Whitaker

AU - Liu, Sophia

AU - Yu, Bingfei

AU - Dorrestein, Pieter C.

AU - Fraenkel, Ernest

AU - Davidson, Shawn M.

AU - Tu, William B.

AU - Kennedy, Brian K.

AU - Lyssiotis, Costas A.

AU - Mullen, Peter J.

PY - 2026/2/3

Y1 - 2026/2/3

N2 - Humans are living longer and experiencing more age-related diseases, many of which involve metabolic dysregulation, but how metabolism changes in multiple organs during aging is not known. Answering this could reveal new mechanisms of aging and therapeutics. Here, we profile metabolic changes in 12 organs in male and female mice at 5 different ages. We also develop organ-specific metabolic aging clocks that identify metabolic drivers of aging, including alpha-ketoglutarate, previously shown to extend lifespan in mice. We also use the clocks to uncover that carglumic acid is a potential driver of aging and show that it is synthesized by human cells. Finally, we validate that hydroxyproline decreases with age in the human pancreas, emphasizing that our approach reveals insights across species. This study reveals fundamental insights into the aging process and identifies new therapeutic targets to maintain organ health.

AB - Humans are living longer and experiencing more age-related diseases, many of which involve metabolic dysregulation, but how metabolism changes in multiple organs during aging is not known. Answering this could reveal new mechanisms of aging and therapeutics. Here, we profile metabolic changes in 12 organs in male and female mice at 5 different ages. We also develop organ-specific metabolic aging clocks that identify metabolic drivers of aging, including alpha-ketoglutarate, previously shown to extend lifespan in mice. We also use the clocks to uncover that carglumic acid is a potential driver of aging and show that it is synthesized by human cells. Finally, we validate that hydroxyproline decreases with age in the human pancreas, emphasizing that our approach reveals insights across species. This study reveals fundamental insights into the aging process and identifies new therapeutic targets to maintain organ health.

UR - https://www.scopus.com/pages/publications/105025168829

UR - https://www.scopus.com/pages/publications/105025168829#tab=citedBy

U2 - 10.1016/j.cmet.2025.10.016

DO - 10.1016/j.cmet.2025.10.016

M3 - Article

C2 - 41297544

AN - SCOPUS:105025168829

SN - 1550-4131

VL - 38

SP - 399-418.e7

JO - Cell Metabolism

JF - Cell Metabolism

IS - 2

ER -

A metabolic atlas of mouse aging

Abstract

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