Stress Biology and Aging Mechanisms: Toward Understanding the Deep Connection Between Adaptation to Stress and Longevity
Open accessAbstract
The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease.
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
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?
Environmental factors such as fewer calories, good sleep, less stress, good relationships, no smoking, and low alcohol drinking can delay aging.
“It was shown that less calories [469], good sleep [470], less stress [471], good relationships [472], no smoke and low alcohol drinking are environmental factors capable of delaying aging, while genetic factors play a role for in 25% to 30% of life expectancy [473].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [471]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Social Relationships and Mortality Risk: A Meta-analytic Review
Holt-Lunstad, J., Smith, T. B., & Layton, J. B. (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000316 · Cited by 7,272 · see citing works
(1996) · Institutional Research Information System University of Turin (University of Turin) · doi:10.1111/j · Cited by 5,486 · see citing works
Adverse childhood experiences, allostasis, allostatic load and age-related disease
Danese, A., & McEwen, B. S. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.08.019 · Cited by 2,140 · see citing works
Brain on stress: how the social environment gets under the skin
McEwen, B. S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121254109 · Cited by 1,200 · see citing works
Dhabhar, F. S., & McEwen, B. S. (1997) · Brain Behavior and Immunity · doi:10.1006/brbi.1997.0508 · Cited by 1,014 · see citing works
Lithgow, G. J., White, T. M., Melov, S., & Johnson, T. E. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7540 · Cited by 862 · see citing works
Self-citationJohnson, F. B., Sinclair, D. A., & Guarente, L. (1999) · Cell · doi:10.1016/s0092-8674(00)80567-x · Cited by 840 · see citing works
The Emerging Field of Human Social Genomics
Slavich, G. M., & Cole, S. W. (2013) · Clinical Psychological Science · doi:10.1177/2167702613478594 · Cited by 523 · see citing works
Good stress, bad stress and oxidative stress: Insights from anticipatory cortisol reactivity
Aschbacher, K., O’Donovan, A., Wolkowitz, O. M., Dhabhar, F. S., Su, Y., & Epel, E. S. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.02.004 · Cited by 459 · see citing works
Self-citationMind over matter: reappraising arousal improves cardiovascular and cognitive responses to stress
Jamieson, J. P., Nock, M. K., & Mendes, W. B. (2012) · Journal of Experimental Psychology: General · doi:10.1037/a0025719 · Cited by 444 · cited 1× · see citing works
“There have however been studies demonstrating “positive stress”—how certain profiles of acute stress responses are related to better physiological health or better cognitive and behavioral performance (7,8).”
BackgroundPsychological and metabolic stress: A recipe for accelerated cellular aging?
Epel, E. S. (2009) · HORMONES · doi:10.14310/horm.2002.1217 · Cited by 422 · see citing works
Self-citationA stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans
Rea, S. L., Wu, D., Cypser, J. R., Vaupel, J. W., & Johnson, T. E. (2005) · Nature Genetics · doi:10.1038/ng1608 · Cited by 411 · see citing works
Growth and chronic disease: findings in the Helsinki Birth Cohort
Barker, D. J. P., Osmond, C., Kajantie, E., & Eriksson, J. G. (2009) · Annals of Human Biology · doi:10.1080/03014460902980295 · Cited by 394 · see citing works
Telomeres and early-life stress: an overview
Price, L. H., Kao, H.-T., Burgers, D. E., Carpenter, L. L., & Tyrka, A. R. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.06.025 · Cited by 339 · see citing works
Social disadvantage, genetic sensitivity, and children's telomere length
Mitchell, C., Hobcraft, J., McLanahan, S. S., Siegel, S. R., Berg, A., Brooks-Gunn, J., Garfinkel, I., & Notterman, D. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1404293111 · Cited by 281 · see citing works
Social regulation of human gene expression: mechanisms and implications for public health
Cole, S. W. (2013) · American Journal of Public Health · doi:10.2105/ajph.2012.301183 · Cited by 225 · see citing works
Biobehavioral Factors and Cancer Progression
Lutgendorf, S. K., & Sood, A. K. (2011) · Psychosomatic Medicine · doi:10.1097/psy.0b013e318235be76 · Cited by 213 · see citing works
Harper, J. M., Salmon, A. B., Leiser, S. F., Gałecki, A. T., & Miller, R. A. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00255.x · Cited by 156 · see citing works
Blackburn, E. H., & Epel, E. S. (2012) · Nature · doi:10.1038/490169a · Cited by 155 · see citing works
Self-citationBourg, É. L. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.01.004 · Cited by 136 · see citing works
Psychological stress and immunoprotection versus immunopathology in the skin
Dhabhar, F. S. (2012) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2011.11.003 · Cited by 128 · see citing works
Metabolic benefits of resistance training and fast glycolytic skeletal muscle
LeBrasseur, N. K., Walsh, K. X., & Arany, Z. P. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00512.2010 · Cited by 119 · see citing works
Establishing cellular stress response profiles as biomarkers of homeodynamics, health and hormesis
Demirovic, D., & Rattan, S. I. S. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.02.005 · Cited by 114 · see citing works
Cell Stress and Aging: New Emphasis on Multiplex Resistance Mechanisms
Miller, R. A. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/gln072 · Cited by 72 · see citing works
Entringer, S., & Wadhwa, P. D. (2013) · Nestlé Nutrition Institute Workshop series · doi:10.1159/000348454 · Cited by 36 · see citing works
Targeting the age‐related occurrence, removal, and accumulation of molecular damage by hormesis
Rattan, S. I. S. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05193.x · Cited by 26 · see citing works
16 Determination of Aging Rate by Coordinated Resistance to Multiple Forms of StressPreprint
Lithgow, G. J., & Miller, R. A. (2008) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969824.51.427 · Cited by 16 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [3]3. Morimoto RI, Cuervo AM. Proteostasis and aging: Five key questions. J Gerontol. In press.
Cited by
Sorted by citations
Social determinants of health and survival in humans and other animals
Snyder-Mackler, N., Burger, J. R., Gaydosh, L., Belsky, D. W., Noppert, G. A., Campos, F. A., Bartolomucci, A., Yang, Y. C., Aiello, A. E., O’Rand, A., et al. (2020) · Science · doi:10.1126/science.aax9553 · Cited by 679 · see citing works
The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
Regulation of longevity by FGF21: interaction between energy metabolism and stress responses
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.05.004 · Cited by 121 · see citing works
Hayashi, T. (2015) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12262 · Cited by 87 · see citing works
Ferroni, P., Riondino, S., Buonomo, O., Palmirotta, R., Guadagni, F., & Roselli, M. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/183928 · Cited by 87 · see citing works
Sabri, B., & Granger, D. A. (2018) · Health Care for Women International · doi:10.1080/07399332.2018.1491046 · Cited by 60 · see citing works
- Authors
- Epel, E. S., & Lithgow, G. J.
- Affiliations
- University of California, San Francisco (US)
- Buck Institute for Research on Aging (US)
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-05-14
- Volume
- 69
- Issue
- Suppl 1
- Pages
- S10-S16
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC4022128
- OpenAlex
- W2061280435
- Cited by
- 223
- References
- 28
- Citations by year
- 2026: 3 · 2025: 23 · 2024: 11 · 2023: 14 · 2022: 16 · 2021: 44 · 2020: 20 · 2019: 21 · 2018: 25 · 2017: 11 · 2016: 15 · 2015: 15 · 2014: 5
- FWCI
- 5.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (AG042053-02, R01 AG0333592-01A1, R01AG030424, R21AG042053)
- National Heart, Lung, and Blood Institute (R01HL108821)
- National Institute of Mental Health (R01MH083784)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- stress biology, biological aging, longevity, toxic stress, stress tolerance, psychological stress, molecular chaperones, stress hormones, inflammation, oxidative stress, insulin, lifespan, chronic disease
- MeSH terms
- Adaptation, Physiological, Aging, Humans, Longevity, Stress, Physiological, Stress, Psychological
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
