P16INK4a Positive Cells in Human Skin Are Indicative of Local Elastic Fiber Morphology, Facial Wrinkling, and Perceived Age.
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.
Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands.
Mariëtte E C
ME
Waaijer
Unilever Discover, Colworth Science Park, Sharnbrook, Bedfordshire.
David A
DA
Gunn
Institute of Cancer Sciences, Cancer Research UK Beatson Laboratories, University of Glasgow.
Peter D
PD
Adams
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee.
Jeff S
JS
Pawlikowski
Centre for Dermatology Research, Salford Royal Hospital, The University of Manchester.
Christopher E M
CE
Griffiths
Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands. Netherlands Consortium for Healthy Aging, Leiden University Medical Center, The Netherlands.
Diana
D
van Heemst
Netherlands Consortium for Healthy Aging, Leiden University Medical Center, The Netherlands. Department of Molecular Epidemiology, Leiden University Medical Center, The Netherlands.
P Eline
PE
Slagboom
Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Rudi G J
RG
Westendorp
Department of Internal Medicine, Section of Gerontology and Geriatrics, VU University Medical Center, Amsterdam, The Netherlands.
Andrea B
AB
Maier
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D016922:Cellular Senescence / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D004547:Elastic Tissue / Q000473:pathology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D015595:Skin Aging / Q000235:genetics* / Q000473:pathology
D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16
Cell senescence; Elastic fiber; Skin; Wrinkle; p16INK4a