# TFEB-mediated lysosome-to-nucleus signaling in aging and lifespan regulation

> **NIH NIH P01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $545,979

## Abstract

Abstract
Aging is characterized by the progressive inability of cells, tissues, and organs to maintain their functional
integrity and is accompanied by an increased susceptibility to morbidity—the odds to develop
neurodegeneration, cancer, or cardiovascular disease increase continuously with age. There is currently no
general, actionable strategy to slow down dysregulation of cell and tissue homeostasis in the aging organism.
As a result, advances in healthcare in the modern era have paradoxically increased frailty and morbidity
among the elderly by increasing lifespan without significantly impacting on age-related homeostasis
dysregulation. Owing to a continuously aging world population, there is therefore an urgent and unmet need to
identify actionable cellular and molecular targets for the development of treatments aimed at increasing
healthspan along with lifespan. Hallmarks of aging are a decline in lysosome-mediated degradation pathways
and chromatin dysregulation. This proposal focuses on a transcription factor EB-mediated lysosome-to-nucleus
signaling pathway, the modulation of which extends mouse lifespan by 30% in males. We will systematically
and mechanistically investigate the three components of this signaling pathway—namely the lysosome, the
signaling transducers, and chromatin regulators—during aging by leveraging unique tools that we have
developed to study lysosomal content and signaling components. Results from this study will provide the first
age-associated atlas of the lysosomal content in the mammalian brain and will pioneer the investigation of
lysosome-to-nucleus signaling in aging. Knowledge resulting from this study could lay the foundation for future
translational investigations of clinical treatment of aging and age-related neurodegenerative disease.

## Key facts

- **NIH application ID:** 10413974
- **Project number:** 5P01AG066606-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Marco Sardiello
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $545,979
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413974

## Citation

> US National Institutes of Health, RePORTER application 10413974, TFEB-mediated lysosome-to-nucleus signaling in aging and lifespan regulation (5P01AG066606-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10413974. Licensed CC0.

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