Social Relationships and Accelerated Aging in Hematopoietic Cell Transplant Survivors

Study Overview
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Brief Summary
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This project aims to elucidate the important protective elements of social relationships and identify concrete, modifiable behavioral factors that contribute to biological and phenotypic aging in hematopoietic cell transplantation (HCT) survivors and can be used to develop biologically informed interventions to improve quality of life and prolong the healthspan of individuals with accelerated aging.

Detailed Description
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PRIMARY OBJECTIVES: I. Examine associations between social support, strain, and isolation and phenotypic aging over the 1-year recovery period. II. Examine associations between social support, strain, and isolation and biological aging over the 1-year recovery period. III. Test biological aging as a mediator linking social processes and phenotypic aging. EXPLORATORY OBJECTIVE: I. Test sex differences in Aims 1 and 2. OUTLINE: Adopting a prospective design, participants will complete comprehensive assessments of social processes at 100 days and 1 year after HCT that combine reports of social support, strain, and isolation with a naturalistic observation tool, the Electronically Activated Recorder (EAR), which captures ambient sound bites to assess social interactions in survivors' daily lives16. At each time point, participants will also provide reports of symptoms to characterize phenotypic aging, including cognitive, physical, and functional complaints, and blood samples to assess biological aging, including cellular senescence, DNA damage, SASP, and cellular stress using genome-wide RNA sequencing. Relevant clinical information that could influence biological aging will also be collected from patients' medical records to consider as covariates.

Official Title
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Accelerated Biological and Phenotypic Aging in Hematopoietic Cell Transplant Survivors: Social Support as a Protective Factor

Conditions
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Hematopoietic and Lymphoid Cell Neoplasm

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Other: Electronic Health Record Review
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years and older who are competent to give their informed consent. Ability to read, speak, and understand English. Received a hematopoietic cell transplant within the previous 100 days. Exclusion Criteria: Less then Aged 18 years and older who are competent to give their informed consent. Cannot read, speak, and understand English. Has not received a hematopoietic cell transplant within the previous 100 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Supportive care (EAR, questionnaires, biospecimen collection)<br>Participants will complete comprehensive assessments of social processes at 100 days and 1 year after HCT that combine reports of social support, strain, and isolation with a naturalistic observation tool, the Electronically Activated Recorder (EAR), which captures ambient sound bites to assess social interactions in survivors' daily lives. At each time point, participants will also provide reports of symptoms to characterize phenotypic aging, including cognitive, physical, and functional complaints, and blood samples to assess biological aging, including cellular senescence, DNA damage, SASP, and cellular stress using genome wide RNA sequencing. Relevant clinical information that could influence biological aging will also be collected from patients' medical records to consider as covariates. | Procedure: Biospecimen Collection<br>* Undergo collection of blood sample<br>Other: Electronic Health Record Review<br>* Review of medical records<br>Other: Questionnaire Administration<br>* Complete questionnaires<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Associations between social support, strain, and isolation and phenotypic aging | Multiple regression models will examine subjective and objective measures of each social process as separate predictors of change in phenotypic aging over the 1-year period, accounting for covariates. | through study completion, an average of 1 year | 
| Associations between social support, strain, and isolation and biological aging | Raw gene expression data will be quantile-normalized and log2-transformed. Similar to Aim 1, multiple regression models will examine each social process as separate predictors of change in cellular senescence marker p16INK4a over the 1-year period, accounting for covariates. Mixed linear models will examine associations between each social process and deoxyribonucleic acid damage response (DDR) and senescence-associated secretory phenotype (SASP) gene profiles, estimated by maximum likelihood to account for systematic differences across genes by treating them as repeated measurements with an unstructured covariance matrix. Bioinformatics analyses will use regression models to identify genes with > 1.5-fold difference. | through study completion, an average of 1 year | 
| Biological aging as a mediator linking social processes and phenotypic aging | A regression-based mediation approach will examine biological aging (p16INK4a messenger ribonucleic acid, DDR and SASP composites) as mediating variables in associations between each social process and change in phenotypic aging, using the PROCESS macro for SPSS statistical software. | through study completion, an average of 1 year |