P16INK4a Positive Cells in Human Skin Are Indicative of Local Elastic Fiber Morphology, Facial Wrinkling, and Perceived Age

J Gerontol A Biol Sci Med Sci. 2016 Aug;71(8):1022-8. doi: 10.1093/gerona/glv114. Epub 2015 Aug 18.

Abstract

Senescent cells are more prevalent in aged human skin compared to young, but evidence that senescent cells are linked to other biomarkers of aging is scarce. We counted cells positive for the tumor suppressor and senescence associated protein p16INK4a in sun-protected upper-inner arm skin biopsies from 178 participants (aged 45-81 years) of the Leiden Longevity Study. Local elastic fiber morphology, facial wrinkles, and perceived facial age were compared to tertiles of p16INK4a counts, while adjusting for chronological age and other potential confounders.The numbers of epidermal and dermal p16INK4a positive cells were significantly associated with age-associated elastic fiber morphologic characteristics, such as longer and a greater number of elastic fibers. The p16INK4a positive epidermal cells (identified as primarily melanocytes) were also significantly associated with more facial wrinkles and a higher perceived age. Participants in the lowest tertile of epidermal p16INK4a counts looked 3 years younger than those in the highest tertile, independently of chronological age and elastic fiber morphology.In conclusion, p16INK4a positive cell numbers in sun-protected human arm skin are indicative of both local elastic fiber morphology and the extent of aging visible in the face.

Keywords: Cell senescence; Elastic fiber; Skin; Wrinkle; p16INK4a.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Aging / metabolism
  • Biomarkers / metabolism
  • Body Mass Index
  • Cellular Senescence / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Elastic Tissue / pathology
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Risk Factors
  • Sensitivity and Specificity
  • Skin / metabolism
  • Skin / pathology*
  • Skin Aging / genetics*
  • Skin Aging / pathology

Substances

  • Biomarkers
  • Cyclin-Dependent Kinase Inhibitor p16