# Sex-Specific Aging Mechanisms

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $371,250

## Abstract

Summary
Sex bias in human disease is common, however underlying mechanisms remain unclear.
Women have immune advantage relative to men, but also greater auto-immune disease
and Alzheimer's Disease. Women's immune advantage is modulated by pregnancy and
correlates with escape from X-chromosome inactivation of several key immune
regulatory genes. In Drosophila females, mating and male Sex Peptide cause increased
reproduction but also inflammation and shortened life span. We have shown that these
effects can be reversed by feeding the human drug mifepristone/RU486, yielding +70%
increase in median life span, and correlated with altered X-linked gene expression,
metabolic re-programming, and altered microbiome. We will test the hypothesis that
female reproductive metabolism makes mitochondria more susceptible to bacterial toxins,
thereby reducing healthspan and life span. We test conserved genes and pathways,
including catecholamine signaling, cholesterol metabolism, and the role of specific
microbial metabolites. Methods include florescent transgenic reporter constructs, high-
throughput sequencing of microbial genomes and fly transcriptomes, 3D video tracking
of fly gene expression and behavior, and testing conserved genes and small molecules for
ability to increase life span and reduce inflammation. AIM 1 investigates mechanisms
including signaling pathway genes and small molecules. AIM 2 investigates metabolome
regulation, and AIM 3 identifies the relevant microbe(s) and metabolites. If successful
this research will identify mechanisms for female-specific aging that might be partly
conserved in humans, and may identify promising genetic targets and drugs for sex-
specific interventions in human inflammation and aging-related disease.

## Key facts

- **NIH application ID:** 10171744
- **Project number:** 5R01AG057741-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** JOHN Gerard TOWER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $371,250
- **Award type:** 5
- **Project period:** 2018-08-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171744

## Citation

> US National Institutes of Health, RePORTER application 10171744, Sex-Specific Aging Mechanisms (5R01AG057741-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10171744. Licensed CC0.

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