Aged mice exhibit widespread metabolic changes but preserved major fluxes
Open accessAbstract
Metabolic dysregulation is a hallmark of aging. Here, we investigate in mice age-induced metabolic alterations using metabolomics and stable isotope tracing. Circulating metabolite fluxes and serum and tissue concentrations were measured in young and old (20-30 months) C57BL/6J mice, with young obese (ob/ob) mice as a comparator. For major circulating metabolites, concentrations changed more with age than fluxes, and fluxes changed more with obesity than with aging. Specifically, glucose, lactate, 3-hydroxybutryate, and many amino acids (but notably not taurine) change significantly in concentration with age. Only glutamine circulatory flux does so. The fluxes of major circulating metabolites remain stable despite underlying metabolic changes. For example, lysine catabolism shifts from the saccharopine toward the pipecolic acid pathway, and both pipecolic acid concentration and flux increase with aging. Other less-abundant metabolites also show coherent, age-induced concentration and flux changes. Thus, while aging leads to widespread metabolic changes, major metabolic fluxes are largely preserved.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Prior work typically centrifuged blood at 17,000-20,000 × g to obtain plasma or serum; these high forces may compromise cell integrity and thereby contribute to potential variability across studies.
“Unlike our studies, prior work typically centrifuged blood at 17,000–20,000 × g to obtain plasma or serum4,73; these high forces may compromise cell integrity and thereby contribute to potential variability across studies.”
From Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages (2026) · cites this paper as [73]
Cites
1 retracted
Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats
Braidy, N., Guillemin, G. J., Mansour, H., Chan-Ling, T., Poljak, A., & Grant, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019194 · Cited by 594 · see citing works
RetractedGlutamine: Metabolism and Immune Function, Supplementation and Clinical Translation
Cruzat, V., Macedo Rogero, M., Noel Keane, K., Curi, R., & Newsholme, P. (2018) · Nutrients · doi:10.3390/nu10111564 · Cited by 1,261 · see citing works
Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D’Amico, D., Ropelle, E. R., Lutolf, M. P., Aebersold, R., et al. (2016) · Science · doi:10.1126/science.aaf2693 · Cited by 1,255 · see citing works
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.013 · Cited by 930 · see citing works
Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis
Seidelmann, S. B., Claggett, B., Cheng, S., Henglin, M., Shah, A., Steffen, L. M., Folsom, A. R., Rimm, E. B., Willett, W. C., & Solomon, S. D. (2018) · The Lancet Public Health · doi:10.1016/s2468-2667(18)30135-x · Cited by 776 · see citing works
Daily energy expenditure through the human life course
Pontzer, H., Yamada, Y., Sagayama, H., Ainslie, P. N., Andersen, L. F., Anderson, L. J., Arab, L., Baddou, I., Bedu-Addo, K., Blaak, E. E., et al. (2021) · Science · doi:10.1126/science.abe5017 · Cited by 583 · see citing works
Wang, Z., Ying, Z., Bosy-Westphal, A., Zhang, J., Schautz, B., Later, W., Heymsfield, S. B., & Müller, M. J. (2010) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2010.29885 · Cited by 546 · see citing works
The metabolic footprint of aging in mice
Houtkooper, R. H., Argmann, C., Houten, S. M., Cantó, C., Jeninga, E. H., Andreux, P. A., Thomas, C., Doenlen, R., Schoonjans, K., & Auwerx, J. (2011) · Scientific Reports · doi:10.1038/srep00134 · Cited by 528 · see citing works
A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice
Roberts, M. N., Wallace, M. A., Tomilov, A. A., Zhou, Z., Marcotte, G. R., Tran, D., Perez, G., Gutierrez-Casado, E., Koike, S., Knotts, T. A., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.005 · Cited by 514 · see citing works
Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice
Newman, J. C., Covarrubias, A. J., Zhao, M., Yu, X., Gut, P., Ng, C.-P., Huang, Y., Haldar, S., & Verdin, E. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.004 · Cited by 493 · see citing works
Elhassan, Y. S., Kluckova, K., Fletcher, R. S., Schmidt, M. S., Garten, A., Doig, C. L., Cartwright, D. M., Oakey, L., Burley, C. V., Jenkinson, N., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.043 · Cited by 448 · see citing works
Slow TCA flux and ATP production in primary solid tumours but not metastases
Bartman, C. R., Weilandt, D. R., Shen, Y., Lee, W. D., Han, Y., TeSlaa, T., Jankowski, C. S. R., Samarah, L., Park, N. R., da Silva-Diz, V., et al. (2023) · Nature · doi:10.1038/s41586-022-05661-6 · Cited by 299 · see citing works
Self-citationAge, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function
Karakelides, H., Irving, B. A., Short, K. R., O'Brien, P., & Nair, K. S. (2010) · Diabetes · doi:10.2337/db09-0591 · Cited by 293 · see citing works
Obesity May Accelerate the Aging Process
Salvestrini, V., Sell, C., & Lorenzini, A. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00266 · Cited by 260 · see citing works
Metabolite exchange between mammalian organs quantified in pigs
Jang, C., Hui, S., Zeng, X., Cowan, A. J., Wang, L., Chen, L., Morscher, R. J., Reyes, J., Frezza, C., Hwang, H. Y., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.002 · Cited by 256 · see citing works
NAD+ flux is maintained in aged mice despite lower tissue concentrations
McReynolds, M. R., Chellappa, K., Chiles, E., Jankowski, C., Shen, Y., Chen, L., Descamps, H. C., Mukherjee, S., Bhat, Y. R., Lingala, S. R., et al. (2021) · Cell Systems · doi:10.1016/j.cels.2021.09.001 · Cited by 112 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages
Guan, C., Ryu, S., Dong, M., Zhu, Y., Maeda, R., Youm, Y.-H., Mohanty, S., Kim, H.-H., Orliaguet, L., Dlugos, T., et al. (2026) · Cell · doi:10.1016/j.cell.2026.09.061
- Authors
- Jankowski, C. S. R., Samarah, L. Z., MacArthur, M. R., Mitchell, S. J., Weilandt, D. R., Hunter, C. J., Zeng, X., McReynolds, M. R., & Rabinowitz, J. D.
- Affiliations
- Princeton University (US)
- Ludwig Cancer Research (US)
- Ludwig Cancer Research (BE)
- Pennsylvania State University (US)
- Corresponding author
- Rabinowitz, Joshua D.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2025-11
- Volume
- 37
- Issue
- 11
- Pages
- 2280-2294.e4
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W4415255428
- Cited by
- 19
- References
- 16
- Citations by year
- 2026: 18 · 2025: 1
- FWCI
- 5.68
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- SSRN Electronic Journal (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK019525)
- Hevolution Foundation (HF-GRO-23-1199192-1)
- Ludwig Institute for Cancer Research Ltd
- Chan Zuckerberg Initiative (2023-331955)
- Calico Life Sciences
- National Institutes of Health
- Diabetes Research Center
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- aging, metabolic flux, circulating metabolites, metabolite concentrations, glucose, lactate, beta-hydroxybutyrate, amino acids, glutamine, lysine catabolism, pipecolic acid, taurine, obesity, C57BL/6J mice
- MeSH terms
- Aging, Amino Acids, Animals, Glucose, Male, Mice, Inbred C57BL, Mice, Obese, Obesity, Lactic Acid, Mice, Metabolomics, Metabolome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
