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Elucidating and targeting T cell senescence-driven immune dysfunction in aging and HIV

Award Number: F30AG097140
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/05/2026
PERIOD OF PERFORMANCE END DATE: 09/04/2027

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Elucidating and targeting T cell senescence-driven immune dysfunction in aging and HIV - T cell senescence is a state of stable cell cycle arrest driven by telomere shortening and DNA damage which is associated with aging. Senescent T cells secrete an array of soluble proteins known as the senescence- associated secretory phenotype (SASP). The accumulation of senescent T cells is hypothesized to drive aging- associated functional decline, inflammaging, and immune impairment. Our group has observed premature T cell senescence and suboptimal immune function in people with HIV (PWH) despite excellent ART-induced virologic suppression. Chronic persistent immune activation from the HIV-1 reservoir is proposed to drive T cell senescence in PWH. We have observed a negative correlation between the frequency of senescent-like T cells and serologic flu vaccine responses, leading us to hypothesize that senescent T cells are linked to adaptive immune decline. A higher prevalence and earlier onset of multiple aging-associated conditions has been observed among PWH, which may be driven by premature T cell senescence. Application of senolytic therapy to clear senescent T cells is a promising strategy to reduce inflammation and immune decline and improve quality of life, which is of critical importance given the rapid demographic aging of the general population and PWH. Aim 1 will determine the complete T cell SASP atlas using fluorescence-activated cell sorting and mass spectrometry. Using highly sensitive multiplex immunoassays, comprehensive knowledge of the T cell SASP will be harnessed to evaluate plasma biomarkers of T cell senescence during physiologic aging and aging with HIV. This aim will provide broad insight into senescent T cell biology and inform the discovery of a T cell SASP-derived immune aging signature. Aim 2 will evaluate the relationship between T cell senescence and immune dysfunction and test interventions to improve immune responses in older age and in aging PWH. This aim will harness high-throughput functional immunology techniques such as spectral flow cytometry, co-culture, and transcriptomics to mechanistically test the effects of aging and HIV on T cell senescence and elucidate the relationship between senescent T cells and cellular and serologic responses to flu vaccination. The findings of Aim 1 will be integrated with those of Aim 2 to provide a clear role for how senescent T cells and the T cell SASP regulate adaptive immune function. The main objective of this fellowship research is to functionally interrogate how senescent T cells influence adaptive immune responses in the context of aging with and without HIV and to aid in the therapeutic application of senolytic drugs to reduce senescent T cell burden to reduce inflammation and immune decline. Completion of this project will provide knowledge and training necessary to build an independent physician-scientist career which integrates areas of immunology, geroscience, and HIV.


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: 2026 ( Subtotal = $54,538 )
2026	2026	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Aging Research	000	1	3/5/2026	NEW	$54,538
														Subtotal = $54,538

Grand Total All Awards = $54,538

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Elucidating and targeting T cell senescence-driven immune dysfunction in aging and HIV

Award Number: F30AG097140

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/05/2026

PERIOD OF PERFORMANCE END DATE: 09/04/2027

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