Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV
About This Grant
PROJECT SUMMARY: Most people living with HIV (PWH) experience premature aging and a reduced healthspan, even while on antiretroviral therapy (ART). However, a unique group of PWH, termed “SuperAgers,” defy these trends, maintaining exceptional healthspan and resilience against aging-associated comorbidities. These individuals provide a unique opportunity to uncover novel mechanisms of healthy aging in PWH. In our recent publication, we found that PWH on ART exhibit elevated levels of senescence-associated glycan- degrading enzymes. These enzymes, namely β-galactosidase and sialidase, degrade the anti-inflammatory glycans, galactose and sialic acid, on circulating glycoproteins. This degradation disrupts anti-inflammatory pathways that normally inhibit excessive NF-κB signaling, to protect against virus-induced inflammation. Consistently, this glycan degradation in PWH correlates with increased inflammation, accelerated biological aging, and a higher prevalence of comorbidities. The therapeutic potential of targeting this mechanism was evident when we inhibited these glycan-degrading enzymes in a humanized mouse model of viremic HIV infection: anti-inflammatory glycans were preserved and both inflammation and biological aging were reduced. While preventing glycan degradation reduces HIV-associated inflammation, a more comprehensive strategy may involve targeting senescent cells directly to mitigate all deleterious consequences of their accumulation. We recently found that accelerated biological age in PWH on ART correlates with elevated expression of urokinase plasminogen activator surface receptor (uPAR), a marker highly expressed on senescent cells. Preclinical studies have shown that targeting uPAR⁺ cells is safe and can selectively eliminate senescent cells and improve healthspan in animal models. However, this approach has not yet been explored in the context of HIV. Together, these findings support our overarching hypothesis: senescence-associated mechanisms, including glycan-degrading enzymes and uPAR overexpression, contribute to inflammaging and premature aging in PWH, are mitigated in SuperAgers, and can be targeted to reduce inflammaging in the context of HIV. We propose two specific aims to address this hypothesis: Aim 1 will determine whether healthy aging during HIV infection is associated with low levels of glycan-degrading enzymes and uPAR, using longitudinal samples from older PWH spanning an aging phenotype gradient, from SuperAgers to individuals with aging-related comorbidities such as cognitive impairment and frailty. Aim 2 will assess whether targeting glycan-degrading enzymes and uPAR can reduce premature aging and inflammaging during ART-suppressed HIV infection using a non-fetal tissue-based humanized mouse model. Together, this study aims to elucidate novel senescence- associated mechanisms that contribute to premature aging in PWH on ART. By targeting uPAR and glycan- degrading enzymes, we also aim to uncover actionable pathways that could inform new therapies to extend healthspan and reduce age-related complications in PWH.
Grant Summary
Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV is a NIA - National Institute on Aging grant providing up to $795K for university, nonprofit, healthcare org. Applications are due 2031-06-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $795K
2031-06-30
- 1Confirm your organization is eligible for Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV from NIA - National Institute on Aging, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIA - National Institute on Aging before the deadline.
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Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV: Frequently Asked Questions
Who is eligible for the Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV?
Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV is offered by NIA - National Institute on Aging and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV provide?
Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV provides up to $795K per award from NIA - National Institute on Aging. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV deadline?
Applications for Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV are due 2031-06-30 (open). Because deadlines can change, verify the date with the funder, NIA - National Institute on Aging, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV?
To apply for Targeting Novel Senescence-Associated Pathways to Combat Premature Aging in People with HIV, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIA - National Institute on Aging.