Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging

Aging Cell. 2009 Aug;8(4):439-48. doi: 10.1111/j.1474-9726.2009.00489.x. Epub 2009 May 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Biomarkers / blood
  • Cyclin-Dependent Kinase Inhibitor p16 / blood*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Exercise
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Middle Aged
  • Smoking
  • T-Lymphocytes / metabolism*
  • Transcription, Genetic


  • Biomarkers
  • Cyclin-Dependent Kinase Inhibitor p16
  • ADP-Ribosylation Factors