# Regulation of the Autophagy Process in Organismal Aging

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2020 · $399,750

## Abstract

PROJECT SUMMARY
Autophagy is a major cellular recycling process by which cytosolic cargo is sequestered and degraded in the
lysosome. This multi-step process plays important roles in development, disease, and aging. Direct links
between autophagy and aging exist in multiple conserved longevity paradigms; such long-lived animals are
thought to induce autophagy in a beneficial manner, yet the underlying mechanisms remain elusive.
 Ours and others' research have firmly established links between autophagy and longevity in the nematode
C. elegans by showing that autophagy genes are required for the long lifespan of all conserved longevity
paradigms tested. Moreover, our unpublished results indicate that autophagy is functionally relevant for
longevity in all major tissues of the long-lived C. elegans mutants we have analyzed so far, and autophagy
generally appears induced in tissues of long-lived mutants, but declines over time in wild-type animals. We and
others have also shown that several transcriptional and post-translational regulators of autophagy play roles in
aging, suggesting that autophagy is subject to complex regulation over time.
 While collectively establishing a critical role for autophagy in multiple tissues of C. elegans, these studies
did not address which tissue-specific functions autophagy may control that affect organismal healthspan.
Moreover, it is unclear how autophagy is temporally and spatially regulated in long-lived mutants and during
normal aging. The goal of this application is to address these gaps in knowledge by using a combination of
genetic, biochemical and behavioral assays primarily in C. elegans, but also in mammalian systems.
Specifically, in Aim 1, we will use quantitative PCR and targeted proteomics to characterize how the autophagy
process is regulated during aging in C. elegans and murine tissues. Moreover, we will use SILAC-coupled
proteomics to measure degradation rates of select autophagy cargos in C. elegans tissues. In Aim 2, we will
analyze tissue-specific roles for autophagy in C. elegans healthspan, and analyze the effects on health- and
lifespan of overexpressing key autophagy-regulatory genes in a temporal and spatial-controlled manner.
Finally, in Aim 3, we will use genetic and biochemical screening approaches to search for new regulators of
autophagy, including factors important for autophagic cargo recognition.
 Autophagy plays critical roles in many diseases, including age-related disorders such as
neurodegeneration. Understanding the regulation of autophagy and the conserved mechanisms by which
autophagy affect aging in multicellular organisms like C. elegans are likely to provide new important insights
not only into aging but may also help develop treatments for such age-related diseases.

## Key facts

- **NIH application ID:** 9918210
- **Project number:** 5R01AG038664-10
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Malene Hansen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,750
- **Award type:** 5
- **Project period:** 2011-08-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918210

## Citation

> US National Institutes of Health, RePORTER application 9918210, Regulation of the Autophagy Process in Organismal Aging (5R01AG038664-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9918210. Licensed CC0.

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