# Mitochondria-cytoskeleton communication and function in aging

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $45,520

## Abstract

Aging affects all living organisms, which is characterized by the loss of cellular homeostasis causing
systemic cellular dysfunction. In fact, both the mitochondrion and the actin cytoskeleton show age-associated
declines in functions. As an organism ages, mitochondria accumulate mtDNA mutations, which result in
mitochondrial dysfunction. The actin cytoskeleton also declines with age. This affects establishment and
maintenance of cell polarity as well as cellular and intracellular movement, which in turn contributes to age-
associated declines in systems including the immune system and skeletal muscle. In addition, many age-
related pathologies like neurodegenerative diseases, such as Alzheimer's, display dysfunction in mitochondria
and actin. Interestingly, Dr. Liza Pon's lab has established actin cytoskeleton dynamics as a contributor to
mitochondrial quality control and asymmetric inheritance of mitochondria during cell division. Specifically, in
yeast as in other organisms babies are born young, largely independent of the age of the mother. The finding
that this process, mother-daughter age asymmetry, occurs in yeast, a single cell organism, led to the model
that aging determinants may be preferentially retained by mother cells and rejuvenating determinants are
preferentially inherited by daughter cells. Our lab has shown that mitochondria are asymmetrically inherited
during yeast cell division and that inheritance of fitter mitochondria by yeast daughter cells is dependent upon
that actin cytoskeleton and necessary for daughter cells fitness and lifespan. We carried out a genome-wide
screen to identify genes who deletion reduced the sensitivity of yeast to the growth inhibiting effects by an actin
destabilizing drug. I obtained evidence for a role of a previously uncharacterized open reading frame identified
in this screen in stabilization of actin cables, promoting mitochondrial function, as well as extension of yeast
lifespan and healthspan. My preliminary evidence also support a role for this gene as a regulator of the TORC1
pathway, a conserved nutrient sensing pathway that regulates lifespan, through its effect on sensing of
branched chain amino acids. Emerging evidence also supports TORC1 in control of actin dynamics. We
propose to study 1) how this gene affects the age-associated changes in actin cables and mitochondria; 2)
whether the lifespan extension observed upon deletion this gene is a consequence of effects on actin cable
stability, retrograde flow and/or mitochondria; 3) whether other interventions that affect actin cables also extend
lifespan, and 4) whether this gene is a novel regulator of lifespan through effect on TORC1.

## Key facts

- **NIH application ID:** 9821173
- **Project number:** 5F31AG055326-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Cierra Nicole Sing
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2017-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9821173

## Citation

> US National Institutes of Health, RePORTER application 9821173, Mitochondria-cytoskeleton communication and function in aging (5F31AG055326-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9821173. Licensed CC0.

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