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

Award Number: F99AG079802
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/30/2022
PERIOD OF PERFORMANCE END DATE: 09/29/2023

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$36,974 )
2024	2023	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Aging Research	000	2	3/27/2024	NON-COMPETING CONTINUATION	-$36,974
2024	2022	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Aging Research	002	1	9/23/2024	NEW	$0
2024	2022	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Aging Research	001	1	3/28/2024	NEW	$0
														Subtotal = -$36,974

Issue Date FY: 2023 ( Subtotal = $36,974 )
2023	2023	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Aging Research	000	2	8/14/2023	NON-COMPETING CONTINUATION	$36,974
														Subtotal = $36,974

Issue Date FY: 2022 ( Subtotal = $37,532 )
2022	2022	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Aging Research	001	1	9/22/2022	NEW	$0
2022	2022	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Aging Research	000	1	9/22/2022	NEW	$37,532
														Subtotal = $37,532

Grand Total All Awards = $37,532

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

Award Number: F99AG079802

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/30/2022

PERIOD OF PERFORMANCE END DATE: 09/29/2023

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