title: Impact of early personal-history characteristics on the Pace of Aging: implications for clinical trials of therapies to slow aging and extend healthspan.
abstract: Therapies to extend healthspan are poised to move from laboratory animal models to human clinical trials. Translation from mouse to human will entail challenges, among them the multifactorial heterogeneity of human aging. To inform clinical trials about this heterogeneity, we report how humans' pace of biological aging relates to personal-history characteristics. Because geroprotective therapies must be delivered by midlife to prevent age-related disease onset, we studied young-adult members of the Dunedin Study 1972-73 birth cohort (n = 954). Cohort members' Pace of Aging was measured as coordinated decline in the integrity of multiple organ systems, by quantifying rate of decline across repeated measurements of 18 biomarkers assayed when cohort members were ages 26, 32, and 38 years. The childhood personal-history characteristics studied were known predictors of age-related disease and mortality, and were measured prospectively during childhood. Personal-history characteristics of familial longevity, childhood social class, adverse childhood experiences, and childhood health, intelligence, and self-control all predicted differences in cohort members' adulthood Pace of Aging. Accumulation of more personal-history risks predicted faster Pace of Aging. Because trials of anti-aging therapies will need to ascertain personal histories retrospectively, we replicated results using cohort members' retrospective personal-history reports made in adulthood. Because many trials recruit participants from clinical settings, we replicated results in the cohort subset who had recent health system contact according to electronic medical records. Quick, inexpensive measures of trial participants' early personal histories can enable clinical trials to study who volunteers for trials, who adheres to treatment, and who responds to anti-aging therapies.
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC, USA.|Social Science Research Institute, Duke University, Durham, NC, USA.|Center for the Study of Aging and Human Development, Duke University, Durham, NC, USA.
authors.forename: Daniel W
authors.identifier: 0000-0001-5463-2212
authors.initials: DW
authors.lastname: Belsky
authors.affiliation: Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.|Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.|Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.|MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
authors.forename: Avshalom
authors.initials: A
authors.lastname: Caspi
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC, USA.|Center for the Study of Aging and Human Development, Duke University, Durham, NC, USA.
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Cohen
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Ramrakha
authors.affiliation: Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand.
authors.forename: Richie
authors.initials: R
authors.lastname: Poulton
authors.affiliation: Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.|Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.|Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.|MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Moffitt
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000375:Aging / Q000502:physiology*; D000076103:Biological Variation, Individual; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003430:Cross-Sectional Studies; D000070497:Healthy Lifestyle / Q000502:physiology*; D006801:Humans; D008016:Life Change Events; D000071421:Life History Traits; D008137:Longitudinal Studies; D008487:Medical History Taking; D023421:Models, Animal; D018579:Patient Selection; D012307:Risk Factors; D012923:Social Class
keywords: biological aging; early-life; geroprotector; geroscience; healthspan; personal history characteristics