Sunday, August 17, 2025 8/17/2025

Reduction of the Beclin1-BCL2 complex in the prevention of HIV and comorbidities associated with aging

Award Number: R21AG090170
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2026

Group Awards By:

View Award Description

Reduction of the Beclin1-BCL2 complex in the prevention of HIV and comorbidities associated with aging - PROJECT SUMMARY The success of combined antiretroviral therapy (cART) has drastically improved the life expectancy of people living with HIV (PLWH). With improved survival among PLWH, many are suffering from age-related neurocognitive complications. HIV-associated inflammation has been implicated in premature aging and increased risk of age-associated comorbidities even in cART-treated individuals. Autophagy, a conserved lysosomal degradation pathway, is known to increase the lifespan of model organisms. We have previously shown that the autophagy protein Beclin1 can regulate viral replication and the secretion of neuroinflammatory molecules in HIV-infected glial cell cultures and an EcoHIV-infected mouse model. Beclin1 interacts via its BH3 domain with the anti-apoptotic Bcl-2 family; thereby inhibiting autophagy. Studies have shown that disrupting the binding between Beclin1 and Bcl-2 can effectively increase autophagy, preventing premature aging, improving health span, and promoting longevity in healthy aged mammals. Thus, the goal of this exploratory grant is to investigate whether increasing autophagy via the inhibition of the Beclin1- Bcl-2 complex formation delays age- related phenotypes and improves cognitive decline associated with HIV in infected adult and old mice. To test our goals, an equal number of male and female Becn1F121A/F121A and C57BL/6J (control) mice at 6 months (Experiment 1) and 16 months of age (Experiment 2) will be infected with EcoHIV or equal volume Saline (control). After 2 weeks a subset of the EcoHIV-infected and Saline animals will receive a daily cocktail of ART and a subset will receive equal volume Saline. In Specific Aim 1, we hypothesize that reduction of the Beclin1– BCL2 complex will improve age-related phenotypes and cognitive decline induced by HIV under ART. In Specific Aim 2, we hypothesize that disrupting the interaction between Beclin1 and Bcl-2 will reduce the expression of key markers of inflammation, oxidative stress, glutamatergic neurotransmission, and altered synaptic plasticity in the pathogenesis of aging and cognitive impairments. The experiments described in this proposal will allow us to determine the role of autophagy in the prevention of age-related neurocognitive complications associated with HIV infection. The success of this study will enhance our knowledge of the mechanism of persistence of neurological complications associated with HIV in the aging population and could lead to the development of a Beclin1-mediated autophagy hyperactivation therapeutic strategy in the prevention of age-related neurocognitive complications associated with HIV infection.


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: 2025 ( Subtotal = $185,000 )
2025	2025	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Aging Research	001	2	8/5/2025	NON-COMPETING CONTINUATION	$185,000
2025	2024	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Aging Research	000	1	10/17/2024	NEW	$0
														Subtotal = $185,000

Issue Date FY: 2024 ( Subtotal = $222,000 )
2024	2024	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Aging Research	000	1	9/20/2024	NEW	$222,000
														Subtotal = $222,000

Grand Total All Awards = $407,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Reduction of the Beclin1-BCL2 complex in the prevention of HIV and comorbidities associated with aging

Award Number: R21AG090170

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer