Year: 2009
Type: article
Study design: Observational Study
Abstract: Expression of the p16(INK4a) tumor suppressor sharply increases with age in most mammalian tissues, and contributes to an age-induced functional decline of certain self-renewing compartments. These observations have suggested that p16(INK4a) expression could be a biomarker of mammalian aging. To translate this notion to human use, we determined p16(INK4a) expression in cellular fractions of human whole blood, and found highest expression in peripheral blood T-lymphocytes (PBTL). We then measured INK4/ARF transcript expression in PBTL from two independent cohorts of healthy humans (170 donors total), and analyzed their relationship with donor characteristics. Expression of p16(INK4a), but not other INK4/ARF transcripts, appeared to exponentially increase with donor chronologic age. Importantly, p16(INK4a) expression did not independently correlate with gender or body-mass index, but was significantly associated with tobacco use and physical inactivity. In addition, p16(INK4a) expression was associated with plasma interleukin-6 concentration, a marker of human frailty. These data suggest that p16(INK4a) expression in PBTL is an easily measured, peripheral blood biomarker of molecular age.
Source: Aging Cell
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Burroughs Wellcome Fund, Ellison Medical Foundation, Wellcome Trust, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Environmental Health Sciences, National Center for Research Resources
Awards: G1050868061, G1476894925, G2244010748, The System of Response to DNA Damage Suppresses Environmental Melanomagenesis, Multidisciplinary Clinical Research Career Develop(RMI), Integrated Training in Cancer Model Systems, Melanoma RAS/BRAF Mutation: Heterogeneity-Risk-Prognosis, The Role of p16INK4 in Mammalian Aging, G7923320676, Bayesian Approaches to Model Selection for Survival Data, G9000031568, G9000121215, Pre- and Postdoctoral Training in Toxicology, G904270447
OpenAlex ID: W2038998835