# Major Depression and Molecular Senescence: The Role of Sleep

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $258,015

## Abstract

Major depressive disorder (MDD) is a significant risk factor for debilitating and costly diseases of aging.
Lifetime exposure to MDD accelerates biological aging, including processes of cellular senescence. We have
identified a cluster of 22 senescence-associated secretory phenotype (SASP) proteins that are significantly
elevated in older adults with remitted MDD and may accelerate biological aging in this vulnerable population.
We have also identified sleep as a modifiable risk factor for accelerated aging and age-related morbidity and
mortality. Our transdisciplinary research team with expertise in the roles of sleep and geriatric depression in
diseases of aging seeks to launch a new systematic program of research that probes sleep as a target for
reducing the impact of depression exposure on accelerated biological aging and its downstream consequences
to health and functioning. We will focus on multidimensional sleep health which has been more strongly
associated with physical health than individual measures of sleep. The proposed study seeks to assay frozen
plasma samples and quantify the SASP in an existing, well-characterized cohort of 135 mid- to late-life adults
with and without a lifetime history of recurrent MDD. Blood samples were collected concurrently with
psychiatric data, multimodal indices of multidimensional sleep health, and participant characteristics.
Consistent with the exploratory nature of the R21 mechanism, the overall aim of the study is to explore the
magnitude and direction of associations among MDD exposure, multidimensional sleep health, and the SASP.
We have three specific aims: (1) To evaluate associations between the SASP and history of MDD; (2) To
evaluate associations between the SASP and multidimensional sleep health; and (3) To examine additive
associations among history of MDD and multidimensional sleep health with the SASP. These preliminary
cross-sectional data will inform the design of, and support the rationale for, planned longitudinal
follow-up studies. In the first follow-up R01, we will experimentally manipulate multidimensional sleep health
per R21 results and evaluate their causal impact on accelerated biological aging in vulnerable adults with a
history of depression. These data will be used, in turn, to develop a sleep-focused senolytic intervention for
evaluation in a randomized clinical trial (second follow-up R01). This iterative program of research will both
advance our scientific understanding of the mechanisms through which MDD increases morbidity and mortality
and inform clinical practice to improve health and reduce risk for diseases of aging in vulnerable adults with a
history of MDD. Ensuring generalizability in future samples will be critical to testing and optimizing the
effectiveness of sleep-related interventions in populations at greatest risk for diseases of aging.

## Key facts

- **NIH application ID:** 10154815
- **Project number:** 1R21AG060732-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Martica Helon Hall
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $258,015
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154815

## Citation

> US National Institutes of Health, RePORTER application 10154815, Major Depression and Molecular Senescence: The Role of Sleep (1R21AG060732-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10154815. Licensed CC0.

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