Accelerated biological and phenotypic aging in hematopoietic cell transplant survivors: Social support as a protective factor

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PROJECT SUMMARY/ABSTRACT Hematopoietic cell transplantation (HCT) is a widely used treatment for hematologic cancers; however, many survivors experience late effects that resemble an accelerated aging phenotype, or age-related functional declines thought to be manifestations of aging at the cellular level. Indeed, emerging evidence suggests that HCT can accelerate biological aging in survivors by up to 15 years. Not all survivors experience these late effects, suggesting that modifiable behavioral factors may influence vulnerability. Given the intense psychological and biological demands of HCT, the recovery period may represent a “window of opportunity” in which behavioral factors such as social support may exert a particular influence. Emerging evidence suggests that social experiences can impact key biological aging pathways in non-cancer populations; however, whether they contribute to variability in accelerated aging in HCT survivors has not been tested. The overarching goal of the proposed research is to examine the influence of social relationships on biological and phenotypic aging in HCT recipients over the first year of recovery. Specifically, this project will: (1) examine associations between social processes and symptoms of phenotypic aging; (2) examine associations between social processes and biological aging; (3) test biological aging as a mediator linking social processes and phenotypic aging; and (4) explore sex differences in associations between social process and biological and phenotypic aging. Adopting a prospective design, this research will comprehensively assess survivors’ social relationships at critical 100-day and 1-year post-HCT time points by combining reports of social support, strain, and isolation with an innovative, in vivo behavioral observation tool, the Electronically Activated Recorder, that captures ambient sound bites to unobtrusively assess social interactions in survivors’ daily lives. Participants will provide reports of symptoms to characterize phenotypic aging, including cognitive, physical (e.g., fatigue, pain, frailty), and functional complaints, and blood samples to assess biological aging pathways, including cellular senescence, inflammation, DNA damage, and oxidative stress assessed via genome-wide transcriptional profiling. This research has the potential to identify concrete, modifiable behavioral targets that contribute to biological and phenotypic aging processes in HCT recipients and can be used to develop biologically informed interventions to improve quality of life and prolong the healthspan of individuals with accelerated aging. This career development award will expand the candidate’s existing expertise in clinical health psychology and behavioral research by providing training in biological and phenotypic aging and functional genomics in the context of cancer survivorship. The proposed research, along with mentorship from a team of expert faculty (Dr. Carroll, Dr. Bower, Dr. Seeman, and Dr. Cole), and the interdisciplinary environment and resources available at UCLA, will prepare the candidate to become a fully independent research scientist in the field of aging and biobehavioral health.