# Mechanism of organelle dysfunction during aging and the related rejuvenation process

> **NIH NIH DP5** · BUCK INSTITUTE FOR RESEARCH ON AGING · 2021 · $485,000

## Abstract

ABSTRACT
 
 Aging is a general physiological deterioration that constitutes the primary risk factor for major human
pathologies, including cancer and neurodegenerative diseases. Research to develop cures for these diseases
has been hampered because we lack a clear understanding of the factors that underlie the aging contribution.
Elucidating these factors remains an important frontier in aging research and will accelerate our ability to
intervene in aging-related diseases. Among these factors, loss of protein homeostasis (proteostasis) and the
consequent accumulation of aggregated proteins represent a major hallmark of aging. Proteostasis is the
guardian of the proteome to ensure proper protein folding, protein-protein interaction, and consequently the
organization of the macromolecules and organelles within a cell. Although proteostasis dysfunction during aging
has been explored in the context of protein aggregation, a largely unknown consequence of proteostasis
dysfunction is the alteration of organelle composition and function. Of relevance to this question, cytosolic protein
aggregates formed upon proteostasis defects are anchored on the surface of mitochondria, which allows
mitochondria to import these aggregated cytosolic proteins. The goals of this work are to 1) understand how
proteostasis defects and aging affect the integrity of mitochondria and other organelles, 2) investigate how
proteostasis defects regulate mitochondrial metabolism, and 3) explore mechanisms to rejuvenate the age-
related mitochondrial dysfunction and proteostasis defects. These Aims will be accomplished by using an
integration of cutting-edge imaging, proteomics, metabolomics, and biochemical technologies to interrogate
related questions in budding yeast, a well-characterized model system for cell biology and aging research. This
work will advance our understanding of aging and age-related diseases that are featured with proteostasis
defects and mitochondrial dysfunction, while establishing the basis for future explorations in the rejuvenation of
aged cells and the interventions for age-related diseases.

## Key facts

- **NIH application ID:** 10239073
- **Project number:** 5DP5OD024598-05
- **Recipient organization:** BUCK INSTITUTE FOR RESEARCH ON AGING
- **Principal Investigator:** Chuankai Zhou
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $485,000
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239073

## Citation

> US National Institutes of Health, RePORTER application 10239073, Mechanism of organelle dysfunction during aging and the related rejuvenation process (5DP5OD024598-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10239073. Licensed CC0.

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