# THE SENDEP STUDY: LINKING MOLECULAR SENESCENCE CHANGES TO DEPRESSION AND COGNITIVE IMPAIRMENT IN LATE LIFE

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2023 · $631,815

## Abstract

Project Summary
Late-life depression (LLD) is a common mental disorder in the elderly, with prevalence rates
ranging from 1 to 5%. Recent evidence suggests that LLD is linked to age-related negative
health outcomes, such as cerebrovascular disease, increased risk of Alzheimer's disease,
vascular dementia, and of premature mortality. The mechanisms of LLD are complex and
involve the dysregulation of different biological pathways. Understanding the interplay between
the biological changes in aging and depression can provide insight into the mechanisms by
which LLD increases the risk of negative health outcomes.
This study proposes to evaluate the association of Senescence-Associated Secretory
Phenotype (SASP) Index with different clinical phenotypes of aging (i.e., cognitive impairment)
and with cellular senescence phenotype (i.e., leukocyte telomere [LT] attrition) in LLD. Finally,
we will evaluate the trajectory of changes in SASP, and its relationship with cognitive
performance in these individuals.
Our hypotheses are that LLD individuals will show a significantly higher SASP index compared
to age- and gender-matched never-depressed control subjects. SASP index will be significantly
associated with greater cognitive impairment and telomere attrition in LLD subjects. We further
hypothesize that an increasing or persistently higher SASP index trajectory will lead to faster
cognitive decline among study participants over two years of follow-up.
To our knowledge, this will be the first study to examine the association between circulating
molecular senescence markers (SASP), a cellular senescence marker (LT attrition), and
neurocognitive and clinical characteristics in LLD. Based on the results of this study, we will also
be able to identify novel targets for the development of interventions aiming not only the
treatment of depression in the elderly but also aiming the prevention of the negative outcomes
related to this condition.

## Key facts

- **NIH application ID:** 10534150
- **Project number:** 5R01MH115953-06
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Breno Satler Diniz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $631,815
- **Award type:** 5
- **Project period:** 2019-02-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10534150

## Citation

> US National Institutes of Health, RePORTER application 10534150, THE SENDEP STUDY: LINKING MOLECULAR SENESCENCE CHANGES TO DEPRESSION AND COGNITIVE IMPAIRMENT IN LATE LIFE (5R01MH115953-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10534150. Licensed CC0.

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