# Accelerated Inflammaging in Schizophrenia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $727,977

## Abstract

Project Summary/Abstract
Schizophrenia (SZ), one of the most disabling mental illnesses, is also associated with increased medical
comorbidity and a 20-year shorter life-span than the general population, which together suggest that SZ is
characterized by accelerated aging. To examine that hypothesis, this application for a 5-year renewal of our
R01 in SZ represents a unique opportunity to evaluate 10-year trajectories of aging in persons with SZ and
healthy comparison subjects (HCs), and to expand the focus to examine serious real world consequences
(physical comorbidity and mortality), potentially modifiable risk factors, and inflammatory and cellular markers
of aging. Per our original proposal, employing a Multi-Cohort Longitudinal Design (MCLD), we have developed
a sex- and age-stratified cohort of 140 subjects with SZ and 120 HCs, aged 26-65 years at baseline. These
participants are evaluated clinically every year, and with a panel of selected markers representative of
biological aging in alternate years. The biomarkers include systemic measures of inflammatory processes
(high-sensitivity C-reactive protein or hs-CRP, along with another cytokine and two chemokines), metabolic
dysregulation (Homeostatic Model Assessment of Insulin Resistance; HOMA-IR), oxidative stress (F2-
isoprostanes), and cellular aging (telomere length). We are currently in the 49th month of the 5-year project, but
are proposing this competitive renewal prior to its completion, to avoid a gap in funding and ensure retention of
this invaluable, well-characterized existing cohort. Our retention rate has been excellent (95% annually for SZ).
We have preliminary evidence consistent with accelerated biological aging in SZ; however, a 10-year
expanded study with additional novel aims and innovative measures is necessary to characterize
consequences and risk factors of acceleration, and examine the mechanistic role of gene expression and
signaling pathways related to inflammation. The proposed renewal has been designed and informed by our
initial findings, and by the evolving literature on inflammation and other biological and cellular mechanisms of
aging. During the next five years, we will continue to evaluate trajectories of the current biomarkers, while
adding novel measures of inflammatory signaling, and inflammation and cellular aging transcriptomic profiles
(“inflammaging”). We will enhance our characterization of physical comorbidity and behaviors, including using
mobile assessment of physical activity and everyday functioning, and increase the frequency of biomarker
assessments to every 18 months. This project is related to the NIMH Strategic Objective # 2: charting mental
illness trajectories to determine when, where, and how to intervene. Demonstrating the presence and
characterizing the patterns of accelerated biological aging in SZ will significantly advance understanding of the
real-world consequences, risk factors, and underlying mechanisms, which together will in...

## Key facts

- **NIH application ID:** 9905421
- **Project number:** 5R01MH094151-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** DILIP V. JESTE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $727,977
- **Award type:** 5
- **Project period:** 2012-05-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9905421

## Citation

> US National Institutes of Health, RePORTER application 9905421, Accelerated Inflammaging in Schizophrenia (5R01MH094151-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9905421. Licensed CC0.

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