The Catabolic—Anabolic Cycling Hormesis Model of Health and Resilience
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A major goal of aging research is to identify ways of extending productive and disease-free lifespans. Here we present the catabolic - anabolic cycling hormesis (CACH) model for optimizing health. The CACH model is based on the concept that cells and organ systems respond to catabolic challenges in ways that bolster their resilience and that an anabolic recovery period is required to effectuate the benefits of the catabolic challenge. As two prominent real-world examples we highlight the literature on the molecular and cellular mechanisms by which physical exercise and intermittent fasting bolster cellular and organismal performance and resilience, and suppress disease processes. Over periods of weeks and months the CACH of exercise and fasting promote optimal health. The hormesis concept is integral to the CACH model and predicts an upper limit to the beneficial effects of catabolic - anabolic cycling that reflects a limit of biological plasticity. This paper extends the hormesis model of health by proposing that 1) it is comprised of two complementary phases: catabolic (adaptive stress responses and conservation of resources) and anabolic (growth and plasticity) and, 2) that CACH is metabolically integrated, quantitatively flexible and dynamically regulated. This model has important implications for future basic and translational research in the fields of aging and related disease processes.
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This cyclical process improves insulin sensitivity and has been suggested to promote mitochondrial biogenesis and efficiency, enhancing aerobic metabolic capacity of myocytes.
“This cyclical process improves insulin sensitivity and has been suggested to promote mitochondrial biogenesis and efficiency, thereby enhancing the aerobic metabolic capacity of myocytes.”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [15]
The CACH model proposes alternation between catabolic stress periods and anabolic recovery phases.
“the CACH model (catabolic–anabolic cycling hormesis) proposes an alternation between catabolic stress periods, such as those induced by physical exercise or starvation, and anabolic recovery phases [15].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [15]
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Strilbytska, O. M., & Lushchak, O. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1778896 · Cited by 4 · see citing works
The psychedelic-peptide paradox: a hormetic hypothesis
Carter, C. S. (2025) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2025.100303 · Cited by 4 · see citing works
“Correspondence on “Hormesis as a Hidden Hand in Global Environmental Change?”” A Reply
Agathokleous, E., & Calabrese, E. J. (2025) · Environmental Science & Technology · doi:10.1021/acs.est.5c05892 · Cited by 3 · see citing works
Traditional Health Practices May Promote Nrf2 Activation Similar to Exercise
Kolb, H., Martin, S., & Kempf, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262311546 · Cited by 3 · see citing works
Zhao, Y. (2026) · Biogerontology · doi:10.1007/s10522-026-10410-7 · Cited by 3 · see citing works
Calabrese, E. J., Pressman, P., Hayes, A. W., Agathokleous, E., Kapoor, R., Calabrese, V., Sun, T., & Dhawan, G. (2026) · Environmental Pollution · doi:10.1016/j.envpol.2026.128523 · Cited by 3 · see citing works
Synergistic effects of vitamins and plant polyphenols on epigenetic regulation of aging
Addissouky, T. A. (2026) · Egyptian Journal of Medical Human Genetics · doi:10.1186/s43042-026-00893-x · Cited by 2 · see citing works
Changing the paradigm: The biggest polluter and threat to your health is your body
Calabrese, E. J. (2026) · Journal of Occupational and Environmental Hygiene · doi:10.1080/15459624.2025.2589127 · Cited by 1 · see citing works
Wang, Y., Gemingnuer, A., Zhang, X., Yin, R., & Meng, X. (2026) · Biogerontology · doi:10.1007/s10522-026-10423-2 · Cited by 1 · see citing works
Calabrese, E. J., Pressman, P., Hayes, A. W., Agathokleous, E., Kapoor, R., Calabrese, V., Sun, T., & Dhawan, G. (2026) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2026.112222 · Cited by 1 · see citing works
Onaka, G. M., Melo, E. S. P., Coronel, P. M. V., Parisotto, E. B., Nascimento, V. A., Souza, A. I., Caputi, R. N. M., Ogura, A. Y., Mendonça, M. L. M., Santos, A. C., et al. (2026) · Nutrire · doi:10.1186/s41110-026-00515-x · Cited by 1 · see citing works
Frailty and COPD: a bidirectional relationship in the context of systemic and accelerated ageing
Maniscalco, M., Candia, C., Fuschillo, S., Ambrosino, P., Komici, K., & Rengo, G. (2026) · European Respiratory Review · doi:10.1183/16000617.0340-2025 · Cited by 1 · see citing works
Tippairote, T., & Hoonkaew, P. (2026) · Frontiers in Network Physiology · doi:10.3389/fnetp.2026.1967461 · Cited by 1 · see citing works
Juan, C. G., & Ntasis, L. (2026) · medRxiv · doi:10.64898/2025.12.26.25343061 · Cited by 1 · see citing works
Emodin: Its effects are largely due to hormesis
Calabrese, E. J., Pressman, P., Hayes, A. W., Agathokleous, E., Dhawan, G., Kapoor, R., & Calabrese, V. (2026) · Food and Chemical Toxicology · doi:10.1016/j.fct.2026.115984
Hormesis: induction by Aloe vera extracts and individual constituents
Calabrese, E. J., Pressman, P., Hayes, A. W., Agathokleous, E., Dhawan, G., Kapoor, R., & Calabrese, V. (2026) · Open Medicine · doi:10.1515/med-2026-1392
Calabrese, E. J., Pressman, P., & Selby, P. B. (2026) · Journal of Occupational and Environmental Hygiene · doi:10.1080/15459624.2026.2640007
Drug Repurposing Opportunities with Phytoecdysteroids: Emerging Trends and Challenges
Usmanov, D. A., Yusupova, U. Y., & Sagdullaev, S. (2026) · Springer eBooks · doi:10.1007/978-981-95-8423-9_9
The hormetic landscape: from evolutionary origination to mechanistic pathways in therapeutics
Verma, H., Gupta, A. K., Hema, G., Yadav, R., Mishra, A. K., Maurya, A., Yadav, J., Mishra, A., Mishra, S., & Prajapati, A. (2026) · Cell Cycle · doi:10.1080/15384101.2026.2716406
Genistein as a potential hormetic regulator of proteostasis in neurodegeneration and aging
Dash, R., Mitra, S., Lee, J., Bashar, M. A., Sohel, M., Tran, N.-N., Lee, J.-C., Lee, S. B., & Lee, B. (2026) · Chinese Medical Journal BioMed · doi:10.65457/cmjbm-2026-0009
Stress, Allostase und Organversagen
Bauer, M. W., & Wetzker, R. (2026) · Die Anaesthesiologie · doi:10.1007/s00101-026-01735-6
Berberine induces pleiotropic beneficial effects via hormesis
Calabrese, E. J., & Kozumbo, W. J. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.109638
Incorporating Hormesis Into Policy: Opportunities, Risks, and Governance Challenges
Agathokleous, E. (2026) · Risk Analysis · doi:10.1111/risa.70375
Ferreira, J. M. A., & Lopes, R. P. (2026) · Stresses · doi:10.3390/stresses6040072
Hormesis as a universal cellular strategy for growth
Agathokleous, E., Markouizou, A., Calabrese, E. J., & Saitanis, C. J. (2026) · Archives of Toxicology · doi:10.1007/s00204-026-04580-z
Is the oxytocin system a keystone in human wellbeing?
Carter, C. S., & Nazarloo, H. P. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1989082
- Authors
- Calabrese, E. J., & Mattson, M. P.
- Affiliations
- University of Massachusetts Amherst (US)
- Johns Hopkins University (US)
- Corresponding author
- Calabrese, Edward J.
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2024-12
- Volume
- 102
- Pages
- 102588
- ISSN
- 1568-1637 (ISSN-L)
- OpenAlex
- W4404412525
- Cited by
- 38
- References
- 84
- Citations by year
- 2026: 26 · 2025: 12
- FWCI
- 1.45
- 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/ (am, 353 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
- Ageing Research Reviews (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- ExxonMobil Foundation (S18200000000256)
- U.S. Air Force
- Air Force Office of Scientific Research (FA9550-19-1-0413)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- hormesis, resilience, aging, lifespan extension, physical activity, intermittent fasting, adaptive stress response, biological plasticity, cellular health, disease suppression
- MeSH terms
- Aging, Animals, Humans, Models, Biological, Exercise, Hormesis
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