title: Biomarker signatures of aging.
abstract: Because people age differently, age is not a sufficient marker of susceptibility to disabilities, morbidities, and mortality. We measured nineteen blood biomarkers that include constituents of standard hematological measures, lipid biomarkers, and markers of inflammation and frailty in 4704 participants of the Long Life Family Study (LLFS), age range 30-110 years, and used an agglomerative algorithm to group LLFS participants into clusters thus yielding 26 different biomarker signatures. To test whether these signatures were associated with differences in biological aging, we correlated them with longitudinal changes in physiological functions and incident risk of cancer, cardiovascular disease, type 2 diabetes, and mortality using longitudinal data collected in the LLFS. Signature 2 was associated with significantly lower mortality, morbidity, and better physical function relative to the most common biomarker signature in LLFS, while nine other signatures were associated with less successful aging, characterized by higher risks for frailty, morbidity, and mortality. The predictive values of seven signatures were replicated in an independent data set from the Framingham Heart Study with comparable significant effects, and an additional three signatures showed consistent effects. This analysis shows that various biomarker signatures exist, and their significant associations with physical function, morbidity, and mortality suggest that these patterns represent differences in biological aging. The signatures show that dysregulation of a single biomarker can change with patterns of other biomarkers, and age-related changes of individual biomarkers alone do not necessarily indicate disease or functional decline.
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA, 02118, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Sebastiani
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, MMC 609 Mayo, 420 Delaware, Minneapolis, MN, 55455, USA.
authors.forename: Bharat
authors.initials: B
authors.lastname: Thyagarajan
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA, 02118, USA.
authors.forename: Fangui
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Epidemiology, Sergievsky Center, Columbia University Mailman School of Public Health, 630 West 168th Street, New York, NY, 10032, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf
authors.affiliation: Department of Epidemiology, University of Pittsburgh, A527 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA, 15261, USA.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.affiliation: Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: Monty
authors.initials: M
authors.lastname: Montano
authors.affiliation: Department of Medicine, Geriatrics Section, Boston University School of Medicine and Boston Medical Center, Robinson 2400, 88 E Newton St, Boston, MA, 02118, USA.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Perls
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D002138:Calibration; D005190:Family; D005260:Female; D006801:Humans; D008136:Longevity / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers
keywords: biological aging; biomarkers; healthy aging; morbidity and mortality