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

项目摘要/摘要 造血细胞移植(Hct)是一种广泛应用于血液病的治疗方法；然而，许多 幸存者经历类似于加速衰老表型或年龄相关功能障碍的迟发效应 衰退被认为是细胞水平上衰老的表现。事实上，新出现的证据表明 HCT可以将幸存者的生物衰老速度加快长达15年。并不是所有的幸存者都经历了这种晚期 影响，这表明可改变的行为因素可能会影响脆弱性。考虑到紧张的 对于HCT的心理和生物需求，恢复期可能代表着#年的“机会之窗”。 哪些行为因素，如社会支持，可能会产生特别的影响。新出现的证据表明 社会经历可以影响非癌症人群中的关键生物衰老途径；然而，是否 它们对HCT幸存者加速衰老的变异性有贡献还没有得到测试。首要目标是 这项研究的目的是考察社会关系对生物学和表型衰老的影响。 在接受HCT治疗的患者康复后的第一年。具体地说，这个项目将：(1)检查协会 社会过程和表型衰老症状之间的关系；(2)检验社会过程和表型衰老症状之间的联系 过程和生物老化；(3)检验生物老化作为连接社会过程和表型的中介 老龄化；以及(4)探讨社会过程与生物学和表型之间的性别差异 衰老。采用前瞻性设计，本研究将全面评估幸存者的社会关系 在HCT后100天和1年的关键时间点，通过结合社会支持、压力和孤立的报告 通过一种创新的活体行为观察工具，电子激活记录器可以捕获 环境声音片段，以不引人注目的方式评估幸存者日常生活中的社交互动。参与者将提供 关于表征表型衰老的症状报告，包括认知、身体(如疲劳、疼痛、虚弱)、 和功能性症状，以及评估生物衰老途径的血液样本，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、可修改的行为目标，这些目标有助于 HCT受者的生物学和表型衰老过程，可用于发展生物信息学 旨在提高生活质量和延长老龄化加速个体健康寿命的干预措施。这 职业发展奖将扩大候选人在临床健康心理学和 通过在生物和表型衰老以及功能基因组学方面提供培训来进行行为研究 癌症生存的背景。拟议的研究，以及专家教职员工团队的指导 (卡罗尔博士、鲍尔博士、西曼博士和科尔博士)以及跨学科环境和资源 在加州大学洛杉矶分校提供，将为候选人在以下领域成为完全独立的研究科学家做好准备 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.