# Elucidate the adverse impact of mitochondria-induced oxidative stress in molecular and cellular determinants in the aging lung, driving susceptibility to Mycobacterium tuberculosis infection

> **NIH NIH F99** · TEXAS BIOMEDICAL RESEARCH INSTITUTE · 2022 · $37,532

## Abstract

PROJECT ABSTRACT
The aging population will double to 2 billion by 2050. Natural lung aging is associated with progressive changes
at molecular and physiological levels, causing a decline in lung function and impaired immunological responses.
To avoid cumulative damage, lung-resident cells rely on a robust homeostatic balance of stress response
pathways; however, at a certain tipping point(s) (point of no return), aging finally overwhelms these control
mechanisms leading to an increased oxidative environment and irreversible damages. Our data indicate that
lung tissue in the elderly (in humans and mice) has high inflammation and oxidative stress baselines, leading to
dysfunction of critical innate soluble and cellular components driving host susceptibility to respiratory infections
[e.g., Tuberculosis (TB) and Coronavirus disease 2019 (COVID-19)]. Defining when and how these changes
occur in the lung at the cellular and molecular levels is critical to understanding age-associated lung-specific
pathologies and aging in general. Our data link mitochondrial dysfunction to cumulative oxidative stress in the
lung of the elderly, where interventions that reduce lung oxidative stress can reverse susceptibility to respiratory
diseases. Mitophagy (mitochondrial autophagy) is also impaired at this stage, resulting in increased
accumulation of oxidative stressors in cells. We now hypothesize that aging-associated mitochondrial
dysfunction and impaired mitophagy is central to the collapse in pulmonary control of mycobacteria. Using the
well-accepted mouse model of aging, this application aims to determine whether aging-associated mitochondrial
dysfunction drives increased oxidative stress in lung cells, generating a permissive lung environment for
respiratory infections such as Mycobacterium tuberculosis, the causative agent of TB. Completing the F99 phase
will facilitate my transition to the postdoctoral phase (K00 phase) by providing robust intellectual and technical
training and, consequently, contributing to my goal of becoming an independent researcher in the biology of
Aging field.

## Key facts

- **NIH application ID:** 10560913
- **Project number:** 1F99AG079802-01
- **Recipient organization:** TEXAS BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** Angelica Milagros Olmo-Fontanez
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $37,532
- **Award type:** 1
- **Project period:** 2022-09-30 → 2023-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10560913

## Citation

> US National Institutes of Health, RePORTER application 10560913, Elucidate the adverse impact of mitochondria-induced oxidative stress in molecular and cellular determinants in the aging lung, driving susceptibility to Mycobacterium tuberculosis infection (1F99AG079802-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10560913. Licensed CC0.

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