Deciphering the decline of metabolic elasticity in aging and obesity
Open accessAbstract
Organisms must adapt to fluctuating nutrient availability to maintain energy homeostasis. Here, we term the capacity for such adaptation and restoration "metabolic elasticity" and model it through ad libitum-fasting-refeeding cycles. Metabolic elasticity is achieved by coordinate versatility in gene expression, which we call "gene elasticity." We have developed the gene elasticity score as a systematic method to quantify the elasticity of the transcriptome across metabolically active tissues in mice and non-human primates. Genes involved in lipid and carbohydrate metabolism show high gene elasticity, and their elasticity declines with age, particularly with PPARγ dysregulation in adipose tissue. Synchronizing PPARγ activity with nutrient conditions through feeding-timed agonism optimizes their metabolic benefits and safety. We further broaden the conceptual scope of metabolic and gene elasticity to dietary challenges, revealing declines in diet-induced obesity similar to those in aging. Altogether, our findings provide a dynamic perspective on the dysmetabolic consequences of aging and obesity.
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Return to normal metabolism following disuse may be blunted in old age, leading to a progressive increase in intramyocellular lipids and decline in muscle performance with every episode of disuse.
“evidence suggests that the return to normal metabolism following disuse may also be blunted in old age (impaired “metabolic elasticity” [81]), leading to a progressive increase in IMCL and decline in muscle performance with every episode of disuse.”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [81]
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Targeting Intramyocellular Lipids to Improve Aging Muscle Function
Russ, D. W., Manickam, R., & Tipparaju, S. M. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-025-02622-6 · Cited by 15 · see citing works
“Furthermore, evidence suggests that the return to normal metabolism following disuse may also be blunted in old age (impaired “metabolic elas-ticity” [81]), leading to a progressive increase in IMCL and decline in muscle performance with every episode of disuse.”
- Authors
- Zhou, Q., Yu, L., Cook, J. R., Qiang, L., & Sun, L.
- Affiliations
- Duke-NUS Medical School (SG)
- Columbia University Irving Medical Center (US)
- Columbia University (US)
- National University of Singapore (SG)
- Corresponding author
- Qiang, Li
- Sun, Lei
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2023-09
- Volume
- 35
- Issue
- 9
- Pages
- 1661-1671.e6
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC10528724
- OpenAlex
- W4386150006
- Cited by
- 80
- References
- 43
- Citations by year
- 2026: 25 · 2025: 36 · 2024: 17 · 2023: 2
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Russell Berrie Foundation
- MOH (MOH-000379, MOH-000954, NMRC/OFIRG/0062/2017)
- Ministry of Education - Singapore (MOE2019-T2-1-025, MOH-000657)
- Ministry of Education
- National Institutes of Health (P01 HL087123, R01DK112943, R01DK128848, R01DK131169)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- aging, obesity, PPARγ, adipose tissue, nutrient availability, energy homeostasis, lipid metabolism, carbohydrate metabolism, diet-induced obesity, transcriptome, non-human primates
- MeSH terms
- Adaptation, Physiological, Adipose Tissue, Aging, Animals, Energy Metabolism, Fasting, Macaca fascicularis, Male, Mice, Inbred C57BL, Obesity, Gene Expression, PPAR gamma, Carbohydrate Metabolism, Lipid Metabolism, Mice
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