The DOI matches its Crossref record; 216 of the 216 references it cites were found in a registry or an index.
The metabolic roots of senescence: mechanisms and opportunities for intervention
Open accessAbstract
Cellular senescence entails a permanent proliferative arrest, coupled to multiple phenotypic changes. Among these changes is the release of numerous biologically active molecules collectively known as the senescence-associated secretory phenotype, or SASP. A growing body of literature indicates that both senescence and the SASP are sensitive to cellular and organismal metabolic states, which in turn can drive phenotypes associated with metabolic dysfunction. Here, we review the current literature linking senescence and metabolism, with an eye toward findings at the cellular level, including both metabolic inducers of senescence and alterations in cellular metabolism associated with senescence. Additionally, we consider how interventions that target either metabolism or senescent cells might influence each other and mitigate some of the pro-aging effects of cellular senescence. We conclude that the most effective interventions will likely break a degenerative feedback cycle by which cellular senescence promotes metabolic diseases, which in turn promote senescence.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The cited source says what the claim attributes to it.
In the citing paper
“The composition and strength of the SASP can vary depending on the duration of senescence, the origin of the senescence stimulus and specific cell types17,21.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [21]
The cited source says what the claim attributes to it.
In the citing paper
“is characterized by morphological and functional changes, including enlarged cell size,9,10 nuclear changes,11,12,13,14,15 metabolic remodeling,16 and the SASP.”
From Cellular senescence in human liver under normal aging and cancer (2026) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Items 201–216 of 216
Stress Responses of Human Dermal Fibroblasts Exposed to Zinc Pyrithione
Rudolf, E., & Cervinka, M. (2011) · Toxicology Letters · doi:10.1016/j.toxlet.2011.04.028 · Cited by 36
Han, J. H., Roh, M. S., Park, C., Park, K. C., Cho, K. H., Kim, K. H., Eun, H. C., & Chung, J. H. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.02.002 · Cited by 35
Kwon, Y.-Y., Lee, S.-K., & Lee, C. (2017) · Molecules and Cells · doi:10.14348/molcells.2017.2279 · Cited by 33
Rapid senescence‐like response after acute injury
Chu, X., Wen, J., & Raju, R. P. (2020) · Aging Cell · doi:10.1111/acel.13201 · Cited by 33
Patschan, S. A., Chen, J., Gealekman, O., Krupincza, K., Wang, M., Shu, L., Shayman, J. A., & Goligorsky, M. S. (2007) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00261.2007 · Cited by 29
Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging
Mau, T., O’Brien, M., Ghosh, A. K., Miller, R. A., & Yung, R. L. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz177 · Cited by 27
Simons, J. (2003) · PubMed · Cited by 25
Chan, K., Yu, M.-H., Lin, M., Huang, C., Chung, D.-J., Lee, Y., Wu, C., & Wang, C. (2016) · Scientific Reports · doi:10.1038/srep38642 · Cited by 25
The Leptomeninges Produce Prostaglandin D2 Involved in Sleep Regulation in Mice
Chérasse, Y., Aritake, K., Oishi, Y., Kaushik, M. K., Korkutata, M., & Urade, Y. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00357 · Cited by 24
Late‐life time‐restricted feeding and exercise differentially alter healthspan in obesity
Schafer, M. J., Mazula, D. L., Brown, A. K., White, T. A., Atkinson, E. J., Pearsall, V. M., Aversa, Z., Verzosa, G., Smith, L. A., Matveyenko, A. V., et al. (2019) · Aging Cell · doi:10.1111/acel.12966 · Cited by 23
Prolonged hypoxia delays aging and preserves functionality of human amniotic fluid stem cells
Casciaro, F., Borghesan, M., Beretti, F., Zavatti, M., Bertucci, E., Follo, M. Y., Maraldi, T., & Demaria, M. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111328 · Cited by 17
Effects of Glucose Restriction on Replicative Senescence of Human Diploid Fibroblasts IMR-90
Jin, J., & Zhang, T. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350090 · Cited by 12
Suppression of p16 induces mTORC1-mediated nucleotide metabolic reprogrammingPreprint
Buj, R., Chen, C., Dahl, E. S., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/393876 · Cited by 9
[Percutaneous treatment of tumors of the upper urinary tract].
Ballanger, P. (1988) · PubMed · Cited by 1
Cited by
Sorted by citations
Mitochondrial dysfunction in cell senescence and aging
Miwa, S., Kashyap, S., Chini, E., & von Zglinicki, T. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158447 · Cited by 1,061
Cellular senescence: a key therapeutic target in aging and diseases
Zhang, L., Pitcher, L. E., Yousefzadeh, M. J., Niedernhofer, L. J., Robbins, P. D., & Zhu, Y. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158450 · Cited by 631
SenNet recommendations for detecting senescent cells in different tissues
Suryadevara, V., Hudgins, A. D., Rajesh, A., Pappalardo, A., Karpova, A., Dey, A. K., Hertzel, A., Agudelo, A., Rocha, A., Soygur, B., et al. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00738-8 · Cited by 408
“Mitochondrial dysfunction-associated senescence is primarily driven by the accumulation of cytosolic NADH, leading to ATP depletion and AMPK activation and cell cycle arrest 21 .”
Self-citationNan, L., Guo, P., Hui, W., Xia, F., & Yi, C. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1592596 · Cited by 84
Roadmap for alleviating the manifestations of ageing in the cardiovascular system
Liberale, L., Tual-Chalot, S., Sedej, S., Ministrini, S., Georgiopoulos, G., Grunewald, M., Bäck, M., Bochaton-Piallat, M.-L., Boon, R. A., Ramos, G. C., et al. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01130-5 · Cited by 59
Metadata
- Authors
- Wiley, C. D., & Campisi, J.
- Affiliations
- Tufts University (US)
- Buck Institute for Research on Aging (US)
- Corresponding author
- Wiley, Christopher D.
- Venue
- Nature Metabolism
- Published
- 2021-10-18
- Volume
- 3
- Issue
- 10
- Pages
- 1290-1301
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC8889622
- OpenAlex
- W3206142581
- Cited by
- 691
- References
- 216
- Citations by year
- 2026: 144 · 2025: 191 · 2024: 163 · 2023: 121 · 2022: 69 · 2021: 2
- FWCI
- 11.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- United States Department of Agriculture | Agricultural Research Service (8050-51000-099-01S)
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (AG051729)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, senescence-associated secretory phenotype, cellular metabolism, metabolic dysfunction, senescence induction, senolytics, metabolic disorders, aging, proliferative arrest
- MeSH terms
- Animals, Autophagy, Homeostasis, Humans, Hyperglycemia, Lysosomes, Metals, NAD, Cellular Senescence
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
