# Cell Aging in Major Depression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $75,144

## Abstract

PROJECT SUMMARY/ABSTRACT
Major depressive disorder (MDD), a disease affecting up to 16% of the U.S. population at some point in their
lives, has been likened to a state of “accelerated aging,” with an increased risk of acquiring certain diseases of
aging and of premature mortality. Evidence consistent with accelerated aging is reported in the brain as well as
in the periphery in MDD. The biological mechanisms underlying this process are beginning to be understood,
largely by studying immune cells with shortened telomeres, which is now reported in several studies of MDD.
Telomeres cap and protect the cell's DNA, and when telomeres become critically short, cells may undergo
apoptosis and die. The body protects telomeres by activating a cellular enzyme, telomerase. Telomerase also
has important roles in cell survival, neurogenesis and, in animal models, intrinsic antidepressant effects. These
latter effects may be mediated via actions in the hippocampus and other brain regions important in MDD. Our
preliminary data suggest that telomerase activity (TA) is important in achieving antidepressant response, and
that TA is correlated with volume of the hippocampus and anterior cingulate gyrus, both of which are implicated
in MDD. A major Aim is to determine whether cell aging in peripheral cells bespeaks a more
generalized process of accelerated cell aging in unmedicated individuals with MDD, focusing on the
brain. In particular, we will determine whether peripheral aging markers (leukocyte telomere length [LTL] and
TA) are significantly correlated with brain structural and biochemical abnormalities in MDD, as detected by
neuroimaging (magnetic resonance imaging [MRI] and magnetic spectroscopic imaging [MRS]); the existence
of such relationships would tie peripheral cell aging to neural abnormalities in MDD. Our neuroimaging focuses
on the corticolimbic network, which is critical in MDD and which showed strong relationships with cell aging
markers in our preliminary data. Our other major Aim is to determine whether the relationship between
changes in depression ratings and in cell aging markers during antidepressant treatment is mediated
by changes in MRS indices (N-acetyl aspartate, a marker of neuronal integrity, and choline-containing
metabolites related to glial metabolism and membrane breakdown). To accomplish this, we will recruit 48 un-
medicated individuals with MDD and assess LTL and TA, along with depression ratings and MRI and MRS.
Depressed individuals will then be treated with an antidepressant for 8 weeks and baseline procedures will be
repeated. We will determine the relationship between cell aging markers, MDD symptoms and corticolimbic
network disturbances as well as between their changes with treatment. Controls will be assessed at baseline
and 8 weeks to assess natural changes in measures over time. Accomplishing these Aims will aid in
developing a new mechanistic understanding of the MDD pathophysiology, which would link neural patholo...

## Key facts

- **NIH application ID:** 10162893
- **Project number:** 3R01MH083784-10S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Elissa S. Epel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $75,144
- **Award type:** 3
- **Project period:** 2008-07-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162893

## Citation

> US National Institutes of Health, RePORTER application 10162893, Cell Aging in Major Depression (3R01MH083784-10S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10162893. Licensed CC0.

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