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

项目概要/摘要 造血细胞移植（HCT）是一种广泛用于血液癌症的治疗;然而，许多造血干细胞移植（HCT）是一种非常有效的治疗方法。 幸存者经历类似于加速老化表型或年龄相关功能的晚期效应， 细胞水平的衰老表现。事实上，新出现的证据表明， HCT可以加速幸存者的生物衰老长达15年。并不是所有的幸存者都经历过 影响，这表明可改变的行为因素可能会影响脆弱性。考虑到 HCT的心理和生物学需求，恢复期可能代表一个“机会之窗”， 哪些行为因素如社会支持可能会产生特定的影响。新出现的证据表明 社会经历可以影响非癌症人群的关键生物衰老途径;然而， 它们对HCT存活者加速老化的可变性的贡献尚未得到测试。总体目标 这项研究的目的是检验社会关系对生物和表型衰老的影响 在HCT接受者恢复的第一年。具体而言，本项目将：（1）研究协会 社会过程和表型衰老症状之间的联系;（2）检查社会过程和表型衰老症状之间的联系。 过程和生物老化;（3）测试生物老化作为连接社会过程和表型的中介 年龄;（4）探索社会过程与生物和表型之间的关联的性别差异 衰老本研究采用前瞻性设计，对幸存者的社会关系进行全面评估 在HCT后关键的100天和1年时间点，通过结合社会支持、紧张和隔离的报告 一个创新的，在体内的行为观察工具，电子激活记录器， 环境声音片段，以不引人注目地评估幸存者日常生活中的社会互动。参与者将提供 表征表型衰老的症状报告，包括认知，身体（例如，疲劳、疼痛、虚弱）， 和功能性投诉，以及血液样本，以评估生物老化途径，包括细胞 通过全基因组转录评估衰老、炎症、DNA损伤和氧化应激 侧写这项研究有可能确定具体的，可改变的行为目标，有助于 HCT接受者的生物学和表型衰老过程，可用于开发生物学信息 采取干预措施，提高加速老化者的生活质量，延长其健康寿命。这 职业发展奖将扩大候选人在临床健康心理学方面的现有专业知识， 通过提供生物学和表型衰老以及功能基因组学方面的培训， 癌症生存的背景。这项拟议中的研究，沿着来自专家团队的指导 (Dr.卡罗尔、鲍尔博士、西曼博士和科尔博士），以及跨学科的环境和资源 可在加州大学洛杉矶分校，将准备候选人成为一个完全独立的研究科学家在该领域的 衰老和生物行为健康。

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.