From Ancient Pathways to Aging Cells—Connecting Metabolism and Cellular Senescence
Open accessAbstract
Cellular senescence is a complex stress response that permanently arrests the proliferation of cells at risk for oncogenic transformation. However, senescent cells can also drive phenotypes associated with aging. Although the senescence-associated growth arrest prevents the development of cancer, and the metabolism of cancer cells has been studied in depth, the metabolic causes and consequences of cellular senescence were largely unexplored until recently. New findings reveal key roles for several aspects of cellular metabolism in the establishment and control of senescent phenotypes. These discoveries have important implications for both cancer and aging. In this review, we highlight some of the recent links between metabolism and phenotypes that are commonly associated with senescent cells.
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Senescent cell fate can be triggered by many stressors, including DNA damage, oncogene activation, mitochondrial dysfunction, reactive metabolites, oxygen extremes, proteotoxic stress, extracellular signals, infections, mechanical or shear stress, resistance exercise, and factors secreted by other senescent cells.
“The senescent cell fate can be triggered by a number of stressors including DNA damage, cancerous mutations or oncogene activation, mitochondrial dysfunction, reactive metabolites, hyperoxia or hypoxia, proteotoxic stress, extracellular signals, infections, mechanical or shear stresses that deform cells, resistance exercise and factors secreted by other senescent cells18,38–47.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [43]
The Introduction says that diverse stresses and physiological signals induce senescence, and the sections on mitochondrial dysfunction and oncogene-induced senescence identify those specific triggers. The copy also discusses genotoxic stress and ROS, but the passages do not establish the full attributed list, particularly infections, mechanical or shear stress, resistance exercise, and hypoxia as triggers. No page numbers were supplied for these sections. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn some respects, senescent cells resemble non-dividing cancer cells, including apoptosis resistance and metabolic shifts.
“In some respects, senescent cells are like non-dividing cancer cells, including apoptosis resistance and metabolic shifts [7, 11, 28, 57–59].”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [58]
Senescent cells display a very active but altered metabolism, with increased glycolysis and mTOR activity.
“Although senescent cells do not divide, they display a very active but altered metabolism, with increased glycolysis and mTOR activity [204].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [204]
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Increased glycolysis in ageing cultured human diploid fibroblasts
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SPOP E3 Ubiquitin Ligase Adaptor Promotes Cellular Senescence by Degrading the SENP7 deSUMOylase
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ATM and LKB1 dependent activation of AMPK sensitizes cancer cells to etoposide-induced apoptosis
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Senescence-inducing stress promotes proteolysis of phosphoglycerate mutase via ubiquitin ligase Mdm2
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Comprehensive analysis of the ubiquitinome during oncogene-induced senescence in human fibroblasts
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Hallmarks of Cellular Senescence
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Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines
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Senolytic drugs: from discovery to translation
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Cellular senescence and senolytics: the path to the clinic
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Measuring biological aging in humans: a quest
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Senescence and cancer — role and therapeutic opportunities
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Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787 · see citing works
The metabolic roots of senescence: mechanisms and opportunities for intervention
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Self-citationObesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis
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Mechanisms and Regulation of Cellular Senescence
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Senescence-associated secretory phenotype contributes to pathological angiogenesis in retinopathy
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The placenta in fetal growth restriction: What is going wrong?
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Cellular senescence: the sought or the unwanted?
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Characterization of cellular senescence in aging skeletal muscle
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Cellular Senescence in Postmitotic Cells: Beyond Growth Arrest
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Reducing Senescent Cell Burden in Aging and Disease
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Paracrine roles of cellular senescence in promoting tumourigenesis
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Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis
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Self-citationPeriodontal microorganisms and Alzheimer disease – A causative relationship?
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Small-molecule MDM2 antagonists attenuate the senescence-associated secretory phenotype
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Oncogene-induced senescence: From biology to therapy
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Cellular senescence in gastrointestinal diseases: from pathogenesis to therapeutics
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“62,63 Consistent with these observations, here, we determined that SASP factors mediating changes in aortic stiffness are associated with glucose metabolism (eg, glycolysis).”
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Taking advantage of drug resistance, a new approach in the war on cancer
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Dynamic Metabolic Response to Adriamycin-Induced Senescence in Breast Cancer Cells
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Pericentromeric repetitive ncRNA regulates chromatin interaction and inflammatory gene expression
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- Authors
- Wiley, C. D., & Campisi, J.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Wiley, Christopher D.
- Campisi, Judith
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 23
- Issue
- 6
- Pages
- 1013-1021
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4911819
- OpenAlex
- W2426149297
- Cited by
- 440
- References
- 92
- Citations by year
- 2026: 50 · 2025: 53 · 2024: 51 · 2023: 36 · 2022: 50 · 2021: 50 · 2020: 43 · 2019: 44 · 2018: 38 · 2017: 21 · 2016: 3
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (R37AG009909, R56AG048253)
- Topics
- Health Sciences › Medicine › Physiology › 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, cellular metabolism, aging, oncogenic transformation, cancer metabolism, senescence-associated phenotype
- MeSH terms
- Aging, Animals, Autophagy, Humans, Mitochondria, NAD, Signal Transduction, Cellular Senescence
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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.
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