# Sex-specific regulation of lifespan and metabolism in C. elegans

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $345,400

## Abstract

Project summary
Aging is the process of decline over time that affects all organisms. Understanding the mechanisms behind
the aging process in model systems could ultimately lead to the prevention of age-related decline and
disease in humans. C. elegans is an excellent model system to study aging and many genes and
interventions have been identified that delay aging. For instance, reduction of insulin/IGF1 or removal of
the germline stem cells robustly increases hermaphrodite lifespan.
Sex specific differences in longevity are seen throughout the animal kingdom, including in humans. Even
though C. elegans is an established aging model system, male lifespan has been largely neglected, since
classic single sex group aging experiments used for hermaphrodites dramatically shorten male lifespan.
Single males leave the agar dishes in search of mates making classic aging experiments with males
technically difficult. Using a liquid 96-well aging assay, we propose to test how males respond to mutations
and interventions that are known to extend hermaphrodite lifespan to identify sex-specific differences in
lifespan regulation in C. elegans and characterize how and where these differences occur. So far, we found
at least one intervention, ablation of the germline, elicits a sex specific response: in contrast to
hermaphrodites, male lifespan does not change significantly upon germline loss. Indeed, sex specific
differences are reported for many of the important downstream regulators of hermaphrodite lifespan
regulation. For instance, hormone and insulin signaling, as well as ascarosides, small molecules produced
by the worms, show sex-specific profiles. However, these signals have not been studied in regard to the
effect on lifespan. In this proposal, we aim to first catalog the male lifespan in response to known
hermaphrodite lifespan changing interventions such as mutations in insulin signaling, TOR signaling,
AMPK signaling, and mitochondrial respiratory chain components and interventions such as dietary
restriction and addition of specific ascarosides. In our second aim, we will investigate the molecular
mechanisms behind the observed sex-specific differences. For example, for germline ablation, we will
investigate the metabolic changes that occur (or fail to occur) upon germ cell stem cell loss in
hermaphrodites and males using NMR spectroscopy and HPLC-MS to identify the signal from the germline
stem cells that regulates longevity. Finally, in Aim 3, we will determine the nature and tissue localization of
the sex-specific differences in lifespan using strains with sex reversal in specific tissues. Such research will
help us understand specific processes affect the lifespan of organisms in a sex specific manner.
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## Key facts

- **NIH application ID:** 10442410
- **Project number:** 5R01AG058740-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Veerle Rottiers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $345,400
- **Award type:** 5
- **Project period:** 2018-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442410

## Citation

> US National Institutes of Health, RePORTER application 10442410, Sex-specific regulation of lifespan and metabolism in C. elegans (5R01AG058740-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10442410. Licensed CC0.

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