Hematopoietic stem cell transplantation (HCT) is found to increase expression of a genetic code used to make proteins, leading to a biological aging of immune cells equivalent to 30 years of chronological age, a study published in EBioMedicine has shown.1
Although stem cell transplant is an effective treatment for hematologic cancers, survivors are known to have increased risk for blood problems associated with aging, such as reduced immunity and increased risk for bone marrow failure and blood cancers, years after curative treatment.
A well-known concept in oncology is that people age biologically at different rates, and that overall health status may not correspond with a person’s chronological age, explained William Wood, MD, a University of North Carolina (UNC) Lineberger Comprehensive Cancer Center member and associate professor in the UNC School of Medicine Division of Hematology and Oncology, and lead author of the study.
For this study, the UNC researchers sought to measure the impact of HCT on molecular aging of cells. They collected blood and clinical data from 63 patients older than 18 years undergoing autologous or allogeneic HCT for any hematologic malignancy between 2010 and 2013 at UNC hospitals.
The researchers tracked levels of expression of messenger RNA (mRNA) coding for p16, a protein that increases more quickly with chronological age and serves as an age-related marker. Levels of expression of mRNA coding for p16 in T cells were increased after both autologous and allogeneic HCT compared with patients’ pretransplant levels; however, the increase in levels was 3 times greater in those patients who received autologous HSCT. A biological aging comparable to an additional 30 years of chronological age.
Although no data were obtained making a clear connection between changes in expression of mRNA coding for p16 and T cell function, expression of this marker is “arguably one of the best in vivo marker of cellular senescence and is directly associated with age-related deterioration,” the authors noted.
1. Wood WA, Krishnamurthy J, Mitin N, et al. Chemotherapy and stem cell transplantation increase p16INK4a expression, a biomarker of T-cell aging. EBioMedicine. 2016 Aug 21. [Epub ahead of print]