Research Paper Volume 16, Issue 21 pp 13225—13236
Adolescents and young adults with sickle cell disease exhibit accelerated aging with elevated T-cell p16INK4a expression
- 1 Department of Medicine, Division of Hematology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
- 2 Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
- 3 UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- 4 Sapere Bio, Research Triangle Park, Raleigh-Durham-Chapel Hill, NC 27709, USA
- 5 Department of Pharmaceutical and Clinical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA
- 6 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- 7 Cogent Biosciences, Waltham, MA 02451, USA
Received: June 6, 2024 Accepted: November 4, 2024 Published: November 14, 2024
https://doi.org/10.18632/aging.206152How to Cite
Copyright: © 2024 Wilson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
People living with sickle cell disease (SCD) experience complications indicative of an accelerated aging phenotype typified by early decline in physical function and increased risk for age-related conditions. Cellular senescence, measured by expression of p16INK4a in peripheral T-lymphocytes, is recognized as one of the underlying contributors to organismal aging. To examine if cellular senescence is increased in SCD patients, we cross-sectionally measured and compared expression of p16 mRNA in peripheral blood T lymphocytes in 18 adolescents and young adults with SCD to 27 similarly aged individuals without SCD. Expression of p16 was dramatically higher in individuals with SCD vs. without SCD (10.1 vs. 8.7 log2 p16 units, respectively, p < 0.001) — a gap of 43 years in biological age — consistent with accelerated aging in the SCD population. Race was not associated with the increased p16 expression in the SCD group. These initial results suggest that individuals with SCD have a significantly higher cellular senescence burden which may contribute to premature aging, physiological decline, and excess morbidities. Additional longitudinal assessment and consideration for trials of senolytic therapies among individuals living with SCD and high p16 expression are warranted to improve their health span.