# Towards Developing Biomarkers for Premature Aging in Schizophrenia

> **NIH NIH K99** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $130,598

## Abstract

Project Summary / Abstract
 Cumulative evidence from large-clinical and neuroimaging studies suggests that the pathophysiology of
schizophrenia involves an increased vulnerability to premature aging. However, this knowledge has not been
translated into clinical practice due to the lack of understanding of the biological underpinnings of premature
aging in schizophrenia. Additionally, there remains a current lack of diagnostic tools for detecting and monitoring
individuals who experience premature aging in a clinical setting. This lack establishes the critical need to develop
in vivo biomarkers of premature aging in schizophrenia to provide a novel avenue toward diagnosis and
neuroprotective treatment. The current proposal provides a step to tackling this challenge through a large,
multimodal study of schizophrenia. The central hypotheses state that individuals with schizophrenia are more
vulnerable to premature aging, as indicated by an increased expression of senescence-associated secretory
phenotype (SASP) proteins, and that the increased expression of SASP proteins explains abnormalities in
physical health, cognition, and brain structure in schizophrenia.
 The applicant, Dr. Johanna Seitz-Holland, has access to several cross-sectional datasets, including clinical,
cognitive, blood, structural, and diffusion data, spanning the schizophrenia lifespan. In the K99 phase, she will
utilize data from 80 individuals with early schizophrenia and 80 matched healthy individuals to establish the
increased expression of SASP proteins as a biomarker for increased vulnerability to premature aging in early
course schizophrenia. In the R00 phase, Dr. Seitz-Holland will include data from over 700 individuals (18-85
years) and characterize the role of the increased expression of SASP proteins as a mediator between
schizophrenia, physical health, cognition, and structural brain abnormalities across the lifespan. Successful
completion of these aims will yield several impactful outcomes. The findings will inform the development of a
clinically feasible, minimally invasive, and low-risk biomarker for premature aging. In addition, the findings will
allow the development of a parsimonious hypothesis that accounts for aspects of brain and physical health
deficits. Lastly, they will provide a scientific basis for developing novel neuroprotective treatments.
 Dr. Seitz-Holland’s long-term goal is to conduct translational research to increase the life quality of those with
psychotic disorders. This application builds on her postdoctoral training in multimodal trajectory schizophrenia
studies and complements it with training from world-class experts in the use and analysis of blood biomarker
data and geriatric science. This award will thus provide her with a unique opportunity to develop into an
independent researcher who can effectively conduct multimodal psychiatric studies and translate findings into
the evidence-based diagnosis and treatment strategies needed in clinic...

## Key facts

- **NIH application ID:** 10898917
- **Project number:** 5K99MH131850-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Johanna Seitz-Holland
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $130,598
- **Award type:** 5
- **Project period:** 2023-08-03 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898917

## Citation

> US National Institutes of Health, RePORTER application 10898917, Towards Developing Biomarkers for Premature Aging in Schizophrenia (5K99MH131850-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10898917. Licensed CC0.

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