title: Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging.
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.
authors.affiliation: Department of Genetics, The University of North Carolina School of Medicine, Chapel Hill, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Sanoff
authors.forename: Hyunsoon
authors.initials: H
authors.lastname: Cho
authors.forename: Christin E
authors.initials: CE
authors.lastname: Burd
authors.forename: Chad
authors.initials: C
authors.lastname: Torrice
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Ibrahim
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Thomas
authors.forename: Norman E
authors.initials: NE
authors.lastname: Sharpless
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000097:blood* / Q000235:genetics; D015444:Exercise; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking; D013601:T-Lymphocytes / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; D020727:ADP-Ribosylation Factors