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PMID: 29149257 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?

American journal of epidemiology ·Vol. 187 ·No. 6 ·2018-00-01 ·Pages 1220-1230

Belsky DW, Moffitt TE, Cohen AA, Corcoran DL, Levine ME, Prinz JA, Schaefer J, Sugden K, Williams B, Poulton R, Caspi A

Abstract

The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such "geroprotective" therapies in humans, outcome measures are needed that can assess extension of disease-free life span. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented 7 methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study (New Zealand; persons born 1972-1973). We studied 11 measures in total: telomere-length and erosion, 3 epigenetic-clocks and their ticking rates, and 3 biomarker-composites. Contrary to expectation, we found low agreement between different measures of biological aging. We next compared associations between biological aging measures and outcomes that geroprotective therapies seek to modify: physical functioning, cognitive decline, and subjective signs of aging, including aged facial appearance. The 71-cytosine-phosphate-guanine epigenetic clock and biomarker composites were consistently related to these aging-related outcomes. However, effect sizes were modest. Results suggested that various proposed approaches to quantifying biological aging may not measure the same aspects of the aging process. Further systematic evaluation and refinement of measures of biological aging is needed to furnish outcomes for geroprotector trials.

MeSH Terms
Aging/physiology Biological Clocks Biomarkers Cohort Studies Female Humans Male Middle Aged Telomere Homeostasis
Chemicals
Biomarkers
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Belsky Daniel W
Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina. | Department of Medicine, Division of Geriatrics, Duke University School of Medicine, Durham, North Carolina. | Social Science Research Institute, Duke University, Durham, North Carolina. | Center for the Study of Aging and Human Development, Duke University, Durham, North Carolina.
Moffitt Terrie E
Department of Psychology and Neuroscience, Duke University, Durham, North Carolina. | Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina. | Center for Genomic and Computational Biology, Duke University, Durham, North Carolina. | MRC Social, Genetic, and Developmental Psychiatry Center, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom.
Cohen Alan A
Department of Family Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Canada.
Corcoran David L
Center for Genomic and Computational Biology, Duke University, Durham, North Carolina.
Levine Morgan E
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Prinz Joseph A
Center for Genomic and Computational Biology, Duke University, Durham, North Carolina.
Schaefer Jonathan
Department of Psychology and Neuroscience, Duke University, Durham, North Carolina.
Sugden Karen
Department of Psychology and Neuroscience, Duke University, Durham, North Carolina.
Williams Benjamin
Department of Psychology and Neuroscience, Duke University, Durham, North Carolina.
Poulton Richie
Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand.
Caspi Avshalom
Department of Psychology and Neuroscience, Duke University, Durham, North Carolina. | Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina. | Center for Genomic and Computational Biology, Duke University, Durham, North Carolina. | MRC Social, Genetic, and Developmental Psychiatry Center, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom.
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Article Info
Journal
American journal of epidemiology
Abbr.
Am J Epidemiol
ISSN
1476-6256
DOI
10.1093/aje/kwx346
Published
2018-00-01
Pages
1220-1230
Language
English
Region
United States
NLM ID
7910653
PMCID
PMC6248475
Subset
IM
Grants
NIA NIH HHS · R01 AG049789 · United States
NIA NIH HHS · T32 AG000139 · United States
NIA NIH HHS · P30 AG034424 · United States
CIHR · Canada
NIA NIH HHS · P30 AG028716 · United States
NIH HHS · S10 OD018164 · United States
NIA NIH HHS · R01 AG032282 · United States
Medical Research Council · MR/P005918/1 · United Kingdom
NIA NIH HHS · R21 AG054846 · United States
NIA NIH HHS · R01 AG048895 · United States
NICHD NIH HHS · R03 HD050374 · United States
External Links
PubMed source DOI: 10.1093/aje/kwx346 PMC Full Text View journal details
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