Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging.
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.
Liu
Yan
Y
Department of Genetics, The University of North Carolina School of Medicine, Chapel Hill, USA.
Sanoff
Hanna K
HK
Cho
Hyunsoon
H
Burd
Christin E
CE
Torrice
Chad
C
Ibrahim
Joseph G
JG
Thomas
Nancy E
NE
Sharpless
Norman E
NE
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
D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; D020727:ADP-Ribosylation Factors