# The Role of the Lysosome in Aging

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $335,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Lysosomes are acidic organelles that play major roles in protein turnover, nutrient signaling, and metabolite
storage. Amino acids and ions are compartmentalized in lysosomes, and nutrient-signaling pathways important
for lifespan regulation such as the Target of Rapamycin (TOR) pathway sense nutrients at the lysosomal
surface. Impaired lysosomal function has long been linked to the aging process and development of numerous
age-associated diseases. However, how lysosomal dysfunction contributes to organismal aging is still unclear.
Recent work from our lab has begun to shed light on this question. Using yeast as a model system, we showed
that lysosome failure is a major driver of cellular decline during the aging process, and its collapse leads to
profound mitochondrial dysfunction. Surprisingly, unlike the majority of previous studies that have suggested
that mitochondrial decline caused by lysosome impairment results from decreased lysosomal proteolysis, we
found that mitochondrial dysfunction does not result from loss of protein degradation upon lysosome collapse,
but instead, from the inability of faulty lysosomes to effectively sequester and compartmentalize amino acids.
Based on these results, we propose that failure to spatially compartmentalize amino acids in lysosomes
interferes with mitochondrial function, and serves as an important driver of aging and lysosome-related
disorders. The central goal of this proposal is to test this hypothesis by: 1) identifying mitochondrial deficits in
lysosome-impaired cells; 2) determining what function of the lysosome is important for regulation of
mitochondrial function; 3) elucidating the role of the lysosome-mitochondria connection in aging and
mammalian systems; and 4) defining new pathways that protect cells from lysosome dysfunction. Collectively,
the results of our studies will provide insight into the aspects of lysosome function important for its role in
lifespan preservation and disease prevention.

## Key facts

- **NIH application ID:** 9937642
- **Project number:** 5R01AG061376-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Adam Hughes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $335,500
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937642

## Citation

> US National Institutes of Health, RePORTER application 9937642, The Role of the Lysosome in Aging (5R01AG061376-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9937642. Licensed CC0.

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