Cortisol, DHEAS, and the cortisol/DHEAS ratio as predictors of epigenetic age acceleration

Rafaela S. C. Takeshita,Amber T. Nguyen,Anthony P. Auger,Wilson C J Chung

Published 2025 in Biogerontology (Dordrecht)

ABSTRACT

Cortisol has been widely used as biomarker of stress and aging, but confounding effects and disruption of the hypothalamic–pituitary–adrenal axis can lead to misinterpretation of results based on a single measurement. A possible alternative is the co-measurement of cortisol and the adrenal hormone dehydroepiandrosterone-sulfate (DHEAS), a glucocorticoid antagonist that modulates the stress response. Using data from 969 individuals from the Midlife in the United States study, this study aimed to investigate the influence of age, sex, and self-identified biosocial group (SIBG) on DHEAS, cortisol, and the cortisol/DHEAS ratio, to test whether these hormones add predictive power to epigenetic age estimates, and to compare the performance of these three hormonal measures in predicting epigenetic age acceleration (EAA) using sex epigenetic clocks: Horvath, Horvath’s skin & blood (Horvath2), Hannum, PhenoAge, GrimAge, and DunedinPACE. Our findings revealed that age, sex and SIBG significantly influenced all three hormonal measures. Controlling for these biodemographic factors, we found that the cortisol/DHEAS was the best predictor of epigenetic clocks. There was a significant and positive correlation between cortisol and Hannum epigenetic age, and between cortisol/DHEAS ratio in three out of the six clocks (Hannum, Horvath2, PhenoAge), but no significant associations between DHEAS and epigenetic age. The cortisol/DHEAS ratio also had a significant and positive correlation with Hannum EAA. DHEAS and cortisol were not significantly associated with EAA for any epigenetic clock. Our results reinforce the importance of co-measuring cortisol and DHEAS in studies investigating the effect of stress in aging processes.

PUBLICATION RECORD

Publication year
2025
Venue
Biogerontology (Dordrecht)
Publication date
2025-08-16
Fields of study
Biology, Medicine, Environmental Science
Identifiers
DOI 10.1007/s10522-025-10307-x PMID 40817994 PMCID 12357812
External record
Open on Semantic Scholar
Source metadata
Semantic Scholar, PubMed

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REFERENCES

Determinants of temporal change in telomere length and its associations with chronic complications and mortality in type 2 diabetes: the Fremantle diabetes study phase II
2025cited by this paper
A blood biomarker of the pace of aging is associated with brain structure: replication across three cohorts.
2024cited by this paper
Serotonin, cortisol, and DHEA-S levels in anxious and depressive pregnant women living with HIV
2024cited by this paper
Exploring the Relationships between Lifestyle Patterns and Epigenetic Biological Age Measures in Men
2024cited by this paper
Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort
2024cited by this paper
Biological age estimation using circulating blood biomarkers
2023cited by this paper
A framework of biomarkers for skeletal aging: a consensus statement by the Aging Biomarker Consortium
2023cited by this paper
Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters
2023cited by this paper
Relationship between Serum Cortisol, Dehydroepiandrosterone Sulfate (DHEAS) Levels, and Natural Killer Cell Activity: A Cross-Sectional Study
2023cited by this paper
Discrimination and Cortisol Dynamics among Older African Americans Adults
2023cited by this paper
Measuring stress: a review of the current cortisol and dehydroepiandrosterone (DHEA) measurement techniques and considerations for the future of mental health monitoring
2023cited by this paper
Cortisol Detection Methods for Stress Monitoring in Connected Health
2023cited by this paper
Epigenetic aging and perceived psychological stress in old age
2022cited by this paper
Hormone ratios suffer from striking lack of robustness to measurement error.
2022cited by this paper
Adrenal aging and its effects on the stress response and immunosenescence.
2022cited by this paper
Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia
2022cited by this paper
Preclinical Models of Chronic Stress: Adaptation or Pathology?
2022cited by this paper
Age, adrenal steroids, and cognitive functioning in captive chimpanzees (Pan troglodytes)
2022cited by this paper
DHEA-S production capacity in relation to perceived prolonged stress
2022cited by this paper
Cortisol trajectories measured prospectively across thirty years of female development following exposure to childhood sexual abuse: Moderation by epigenetic age acceleration at midlife.
2021cited by this paper
DunedinPACE, a DNA methylation biomarker of the pace of aging
2021influential reference
The neuroendocrinology of stress: Glucocorticoid signaling mechanisms.
2021cited by this paper
Psychological and biological resilience modulates the effects of stress on epigenetic aging
2021cited by this paper
DHEA as a biomarker of aging in humans and nonhuman primates
2021influential reference
Determination of Biological Age: Geriatric Assessment vs Biological Biomarkers
2021cited by this paper
Beyond Glucocorticoids: Integrating Dehydroepiandrosterone (DHEA) into Animal Welfare Research
2020cited by this paper
GrimAge outperforms other epigenetic clocks in the prediction of age-related clinical phenotypes and all-cause mortality.
2020cited by this paper
effectsize: Estimation of Effect Size Indices and Standardized Parameters
2020cited by this paper
Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up
2020cited by this paper
Assessment of Epigenetic Clocks as Biomarkers of Aging in Basic and Population Research.
2020cited by this paper
Adverse childhood experiences, DNA methylation age acceleration, and cortisol in UK children: a prospective population-based cohort study
2020cited by this paper
The Link between Chronic Stress and Accelerated Aging
2020cited by this paper
The effects of social adversity, discrimination, and health risk behaviors on the accelerated aging of African Americans: Further support for the weathering hypothesis.
2020cited by this paper
A systematic review and meta-analysis of environmental, lifestyle and health factors associated with DNA methylation age.
2019cited by this paper
Relationship between resilience and stress: Perceived stress, stressful life events, HPA axis response during a stressful task and hair cortisol.
2019cited by this paper
DNA methylation GrimAge strongly predicts lifespan and healthspan
2019influential reference
Mechanisms of Racial Health Disparities: Evidence on Coping and Cortisol from MIDUS II
2019cited by this paper
The effect of early discrimination on accelerated aging among African Americans.
2019influential reference
Association of serum cortisol and dehydroepiandrosterone sulfate (DHEAS) levels with psychological stress in patients with vitiligo
2019cited by this paper
AAPA Statement on Race and Racism.
2019cited by this paper
DNA methylation-based biomarkers and the epigenetic clock theory of ageing
2018cited by this paper
Pathways from racial discrimination to cortisol/DHEA imbalance: protective role of religious involvement
2018cited by this paper
Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies
2018cited by this paper
An epigenetic biomarker of aging for lifespan and healthspan
2018influential reference
Chromosomal Processes in Mind-Body Medicine: Chronic Stress, Cell Aging, and Telomere Length
2018cited by this paper
Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress-Related Pathogenesis and Current Challenges in Biomarker Development
2017cited by this paper
Measuring cortisol in serum, urine and saliva – are our assays good enough?
2017cited by this paper
Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume
2017cited by this paper
The role of dehydroepiandrosterone on functional innate immune responses to acute stress
2017cited by this paper
Epigenetic clock analysis in long-term meditators.
2017cited by this paper
Biological Age Predictors
2017cited by this paper
Epigenetic modifications of gene expression by lifestyle and environment
2017cited by this paper
Leukocyte telomere length, T cell composition and DNA methylation age
2017cited by this paper
Accelerated Health Declines among African Americans in the USA
2016cited by this paper
Socioeconomic Status, Race/Ethnicity, and Diurnal Cortisol Trajectories in Middle-Aged and Older Adults
2016influential reference
Molecular and biological hallmarks of ageing
2016cited by this paper
DNA Methylation in Obesity and Associated Diseases
2016cited by this paper
Everyday discrimination and diurnal cortisol during adolescence.
2016cited by this paper
Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling
2015cited by this paper
Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder.
2015cited by this paper
A blunted diurnal cortisol response in the lower educated does not explain educational differences in coronary heart disease: findings from the AGES-Reykjavik study.
2015cited by this paper
Hair cortisol in relation to sociodemographic and lifestyle characteristics in a multiethnic US sample.
2015cited by this paper
Select aging biomarkers based on telomere length and chronological age to build a biological age equation
2014cited by this paper
Testosterone Increases Circulating Dehydroepiandrosterone Sulfate Levels in the Male Rhesus Macaque
2014cited by this paper
Evidence of accelerated aging among African Americans and its implications for mortality.
2014cited by this paper
R: A language and environment for statistical computing.
2014cited by this paper
Perceived stress at work is associated with attenuated DHEA-S response during acute psychosocial stress.
2013cited by this paper
DNA methylation age of human tissues and cell types
2013cited by this paper
Determination of cortisol in serum, saliva and urine.
2013cited by this paper
Perceived Stress at Work Is Associated with Lower Levels of DHEA-S
2013cited by this paper
Genome-wide methylation profiles reveal quantitative views of human aging rates.
2013cited by this paper
Elevated hair cortisol concentrations in endurance athletes.
2012cited by this paper
Environmental Stress Affects DNA Methylation of a CpG Rich Promoter Region of Serotonin Transporter Gene in a Nurse Cohort
2012cited by this paper
Ageing, physical function, and the diurnal rhythms of cortisol and dehydroepiandrosterone.
2012cited by this paper
DNA methylation as a risk factor in the effects of early life stress.
2011cited by this paper
Shift work at young age is associated with elevated long-term cortisol levels and body mass index.
2011cited by this paper
Cortisol and dehydroepiandrosterone-sulphate levels correlate with symptom severity in first-episode psychosis.
2011cited by this paper
Neutrophil function and cortisol:DHEAS ratio in bereaved older adults.
2011cited by this paper
Cortisol in hair measured in young adults - a biomarker of major life stressors?
2011cited by this paper
Reliability of hypothalamic–pituitary–adrenal axis assessment methods for use in population-based studies
2011cited by this paper
Differential inflammatory responses in aging and disease: TNF-alpha and IL-6 as possible biomarkers.
2010cited by this paper
Dehydroepiandrosterone as a regulator of immune cell function.
2010cited by this paper
The cortisol awakening response in context.
2010cited by this paper
Cortisol, DHEAS, their ratio and the metabolic syndrome: evidence from the Vietnam Experience Study.
2010cited by this paper
Low serum levels of dehydroepiandrosterone sulfate predict all-cause and cardiovascular mortality in elderly Swedish men.
2010cited by this paper
Neuroendocrine and Immunological Correlates of Chronic Stress in ‘Strictly Healthy’ Populations
2009cited by this paper
Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS).
2009cited by this paper
Elevated content of cortisol in hair of patients with severe chronic pain: A novel biomarker for stress
2008cited by this paper
Leukocyte Telomere Dynamics: Longitudinal Findings Among Young Adults in the Bogalusa Heart Study
2008cited by this paper
Stress biomarkers' associations to pain in the neck, shoulder and back in healthy media workers: 12-month prospective follow-up
2008cited by this paper
Telomere shortening and ageing of the immune system.
2008cited by this paper
Racial/ethnic differences in cortisol diurnal rhythms in a community sample of adolescents.
2007influential reference
Sex differences in the relationship between DHEAS and health.
2007cited by this paper
Serum Cortisol Levels in Patients Admitted to the Department of Medicine: Prognostic Correlations and Effects of Age, Infection, and Comorbidity
2006cited by this paper
Neuropsychopharmacological properties of neuroactive steroids in depression and anxiety disorders
2006cited by this paper
Biology of Aging
2006cited by this paper
Raised cortisol:DHEAS ratios in the elderly after injury: potential impact upon neutrophil function and immunity
2005cited by this paper
Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism compared with urinary free cortisol and overnight dexamethasone suppression test.
2005cited by this paper
Depressive Symptoms Are Associated With Blunted Cortisol Stress Responses in Very Low-Income Women
2005cited by this paper
Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells.
2005cited by this paper