TY - JOUR
T1 - The Cutting Edge of Epigenetic Clocks
T2 - In Search of Mechanisms Linking Aging and Mental Health
AU - Harvanek, Zachary M.
AU - Boks, Marco P.
AU - Vinkers, Christiaan H.
AU - Higgins-Chen, Albert T.
N1 - Funding Information: This work was supported by the National Institute of Mental Health Clinical Neuroscience Research Training in Psychiatry grant (Grant No. T32MH019961 [to ZMH]), Yale University McNeil Fellowship (to ZMH), Yale University Thomas P. Detre Fellowship Award in Translational Neuroscience Research (to ZMH and ATH-C), Netherlands Organisation for Health Research and Development Vidi grant (Grant No. 09150171910042 [to CHV]), National Institutes of Health National Institute on Aging (Grant Nos. 1R01AG065403, 1R01AG057912, 5R01AG060110, and 1R01AG068937 [to ATH-C]). The sponsors had no role in conceptualization, preparation, review, approval, or submission of the manuscript. All authors researched the literature, contributed to discussions of the content, and wrote the manuscript. ATH-C formulated the initial concept for the review and coordinated all authors in writing. Different authors focused on writing different parts: introduction (ZMH, ATH-C), mechanisms of aging (ATH-C), stress (ZMH, ATH-C), schizophrenia (MPB, CHV, ATH-C), figures (ZMH, ATH-C), conclusions (ZMH, MPB, CHV, ATH-C). All authors contributed to editing all sections. ATH-C received consulting fees from FOXO Technologies and TruDiagnostic concerning epigenetic clocks. ATH-C is named on two epigenetic clock inventions owned by Yale University. A clock based on the PC clock methodology is licensed to Elysium Health. None of these commercial entities were involved in the conceptualization, preparation, review, approval, or submission of this manuscript. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the National Institute of Mental Health Clinical Neuroscience Research Training in Psychiatry grant (Grant No. T32MH019961 [to ZMH]), Yale University McNeil Fellowship (to ZMH), Yale University Thomas P. Detre Fellowship Award in Translational Neuroscience Research (to ZMH and ATH-C), Netherlands Organisation for Health Research and Development Vidi grant (Grant No. 09150171910042 [to CHV]), National Institutes of Health National Institute on Aging (Grant Nos. 1R01AG065403, 1R01AG057912, 5R01AG060110, and 1R01AG068937 [to ATH-C]). The sponsors had no role in conceptualization, preparation, review, approval, or submission of the manuscript. Publisher Copyright: © 2023 Society of Biological Psychiatry
PY - 2023/11/1
Y1 - 2023/11/1
N2 - Individuals with psychiatric disorders are at increased risk of age-related diseases and early mortality. Recent studies demonstrate that this link between mental health and aging is reflected in epigenetic clocks, aging biomarkers based on DNA methylation. The reported relationships between epigenetic clocks and mental health are mostly correlational, and the mechanisms are poorly understood. Here, we review recent progress concerning the molecular and cellular processes underlying epigenetic clocks as well as novel technologies enabling further studies of the causes and consequences of epigenetic aging. We then review the current literature on how epigenetic clocks relate to specific aspects of mental health, such as stress, medications, substance use, health behaviors, and symptom clusters. We propose an integrated framework where mental health and epigenetic aging are each broken down into multiple distinct processes, which are then linked to each other, using stress and schizophrenia as examples. This framework incorporates the heterogeneity and complexity of both mental health conditions and aging, may help reconcile conflicting results, and provides a basis for further hypothesis-driven research in humans and model systems to investigate potentially causal mechanisms linking aging and mental health.
AB - Individuals with psychiatric disorders are at increased risk of age-related diseases and early mortality. Recent studies demonstrate that this link between mental health and aging is reflected in epigenetic clocks, aging biomarkers based on DNA methylation. The reported relationships between epigenetic clocks and mental health are mostly correlational, and the mechanisms are poorly understood. Here, we review recent progress concerning the molecular and cellular processes underlying epigenetic clocks as well as novel technologies enabling further studies of the causes and consequences of epigenetic aging. We then review the current literature on how epigenetic clocks relate to specific aspects of mental health, such as stress, medications, substance use, health behaviors, and symptom clusters. We propose an integrated framework where mental health and epigenetic aging are each broken down into multiple distinct processes, which are then linked to each other, using stress and schizophrenia as examples. This framework incorporates the heterogeneity and complexity of both mental health conditions and aging, may help reconcile conflicting results, and provides a basis for further hypothesis-driven research in humans and model systems to investigate potentially causal mechanisms linking aging and mental health.
KW - Aging
KW - Biomarkers
KW - Clocks
KW - Epigenetics
KW - Schizophrenia
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=85152667070&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.biopsych.2023.02.001
DO - https://doi.org/10.1016/j.biopsych.2023.02.001
M3 - Review article
C2 - 36764569
SN - 0006-3223
VL - 94
SP - 694
EP - 705
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 9
ER -