In an ambitious bid to revolutionize how we approach aging and its related ailments, the University of Rochester spearheads a pioneering research initiative, backed by a generous investment of approximately $22 million from the Advanced Research Projects Agency for Health (ARPA-H). Unlike conventional medical treatments that tackle diseases upon their emergence, this novel project addresses the root cause of aging — a fundamental biological process that drives the deterioration of health, strength, and cognitive function in the elderly.
The present research endeavor explores the potential of repurposing an HIV drug, originally designed to inhibit viral replication, to target and suppress an intrinsic immune response triggered not by external pathogens but by the body’s own DNA elements. These elements, known as retrotransposons, resemble ancient viral sequences embedded in our genome and have long been implicated in genetic instability and tissue aging processes. Their aberrant activation with age prompts chronic inflammation, a risky “false alarm” that erodes physiological resilience.
ARPA-H’s PROactive Solutions for Prolonging Resilience (PROSPR) program funded this extensive research with the goal of uncovering transformative biomedical interventions. By attacking the molecular underpinnings of aging itself, the project aspires to fundamentally alter the trajectory of age-associated decline and chronic disease manifestation. The University of Rochester’s team, led by Professor Vera Gorbunova, integrates expertise across molecular biology, immunology, and gerontology, joining forces with distinguished collaborators from institutions including Brown University and the University of Connecticut.
Central to the investigation is the phenomenon wherein retrotransposons, specifically LINE-1 elements, awaken from their normally repressed state during aging. Gorbunova’s prior landmark studies unearthed that these genetic “jumping genes” can activate interferon signaling—a critical antiviral defense mechanism. This spurious activation mimics the cellular response to viral infections, fomenting a persistent state of low-grade inflammation. This chronic inflammatory milieu has been increasingly correlated with the progression of neurodegenerative diseases, oncogenesis, metabolic disorders, and autoimmune dysfunction.
The hypothesis underpinning this research posits that by pharmacologically dampening retrotransposon activity, one can quell the inflammatory cascade, thereby attenuating the biological aging process. The drug TPN-101, also known as Censavudine, functions as a reverse transcriptase inhibitor—a mechanism mirroring its utility in suppressing HIV replication. Reverse transcriptase is the enzyme employed by retrotransposons to copy and propagate themselves within the genome. By impeding this enzyme, the drug effectively silences the retrotransposons, potentially halting their capacity to provoke detrimental immune responses.
Before advancing to human trials, the team will rigorously test TPN-101 in animal models to evaluate its long-term safety and efficacy in mitigating inflammation and preserving tissue integrity. Following these preclinical studies, the research transitions into a randomized, double-blind clinical trial involving 200 healthy participants between the ages of 60 to 65. The trial, under the clinical leadership of Kathi Heffner, will administer the drug or placebo over 48 weeks while monitoring an array of biomarkers reflective of biological aging.
A key innovative measure employed in the clinical study is the assessment of intrinsic capacity, an integrative metric endorsed by the World Health Organization encompassing multiple facets of health including physical mobility, cognitive function, vitality, sensory acuity, and psychological well-being. Supplementing this approach, molecular aging markers and physical performance tests will elucidate the drug’s impact on the participant’s healthspan—the period of life spent in good health.
The implications of this research extend far beyond symptomatic treatment, opening avenues for interventions that target the aging process itself, a paradigm shift heralding a new era in biomedical science. If successful, it would confer profound societal benefits by enabling individuals to maintain independence, productivity, and cognitive sharpness into later life stages, thereby alleviating the enormous burden of age-related diseases on healthcare systems globally.
Dr. Gorbunova emphasizes the significance of this interdisciplinary collaboration, combining molecular biology insights and clinical expertise to translate basic scientific discoveries into tangible health solutions. The exploration of DNA-derived “false alarms” in cellular immunity injects fresh understanding into the biological aging narrative, offering a compelling target to combat the insidious effects of age-driven inflammation.
Such innovative research underscores the role of large-scale, public-private funding mechanisms like ARPA-H in fueling high-risk, high-reward biomedical projects. Its investment in cutting-edge science aims to propel therapeutic advances that could redefine medical practice and improve quality of life on a global scale. University President Sarah Mangelsdorf highlights the synergistic effect of this support and recognizes the University of Rochester’s leadership in harnessing biomedical innovation toward human health enhancement.
The study also broadens the therapeutic horizon by repurposing existing pharmaceuticals with established safety profiles, accelerating the pathway to market availability compared to novel drug development. TPN-101’s prior use in HIV treatment provides an advantage in understanding dosage tolerance and pharmacodynamics, facilitating a smoother transition into geriatric clinical applications.
Ultimately, this research promises to pivot the scientific community’s approach to aging—from reactive disease treatment to proactive resilience extension. By tuning down the genomic elements that mislead cellular immune systems, this intervention could shield older adults from the relentless march of inflammation-induced dysfunction, sustaining their vigor and mental acuity far beyond traditional expectations.
As the clinical trial unfolds over the coming years, the data generated will illuminate the feasibility and efficacy of targeting retrotransposon activity as a revolutionary strategy against biological aging. This endeavor exemplifies a visionary step towards transforming aging from an inevitable decline into a manageable biological state, heralding hope for healthier aging populations worldwide.
Subject of Research: Biological mechanisms underpinning aging and chronic inflammation triggered by retrotransposon activity; evaluation of reverse transcriptase inhibitor TPN-101 (Censavudine) as an intervention to extend healthspan.
Article Title: University of Rochester Leads Groundbreaking Study to Combat Aging with HIV Drug Repurposing
News Publication Date: Not specified in the source material.
Web References:
– University of Rochester: http://www.rochester.edu/
– ARPA-H PROSPR Program: https://arpa-h.gov/explore-funding/programs/prospr
– Department of Biology, University of Rochester: https://www.sas.rochester.edu/bio/index.html
– Rochester Aging Research Center: https://www.urmc.rochester.edu/university-of-rochester-aging-institute/research/roar-center
– Upstate NY Comparative Biology of Aging Nathan Shock Center: https://www.rochester.edu/newscenter/nathan-shock-center-comparative-biology-aging-upstate-ny-660182/
– School of Nursing, University of Rochester: https://son.rochester.edu/index.html
– Resilience Research Center: https://www.rochester.edu/university-research/initiatives/university-of-rochester-resilience-research-center-ur%C2%B3c/
– University of Rochester Medical Center: https://www.urmc.rochester.edu/
References:
– Gorbunova, V., et al., studies on LINE-1 retrotransposons and interferon signaling, University of Rochester News Center: https://www.rochester.edu/newscenter/selfish-genetic-elements-amplify-inflammation-and-age-related-diseases-367632/
Image Credits: Not provided.
Keywords: Molecular biology, Inflammation, Immunology, Molecular genetics, DNA damage, Drug development
Tags: age-related cognitive declineaging research fundingARPA-H aging initiativebiomedical interventions for agingchronic inflammation in elderlygenetic instability in agingHIV drug repurposing for agingimmune response and agingmolecular mechanisms of agingPROSPR program aging studyretrotransposons and agingUniversity of Rochester aging research
