Andrew Nguyen, PhD | Saint Louis University; Susan Farr, PhD
Competition Sponsor:National Academy of Medicine
Awardee Year: 2024
Aging is a major risk factor for many chronic diseases as well as geriatric syndromes, and therapeutics that delay or slow the progression of aging remain elusive. There is great potential to enhance healthspan and longevity with novel pharmacological interventions based on genetics. We propose to use an emerging therapeutic modality – antisense oligonucleotides (ASOs) – to selectively modulate levels of longevity-associated genes. This could fill a gap in the translation of decades of genetic studies on aging into targeted pharmacological interventions.
Over the past three decades, genetic studies in model organisms and humans have identified and validated gene mutations and variants that prolong lifespan and enhance healthspan. Together, these findings show that modest changes in expression and/or activity of these genes can have a significant impact on aging and longevity. ASOs are emerging as a promising therapeutic modality, and they enable decreasing the expression of target genes in a specific manner in vivo. Importantly, we developed a novel ASO-based strategy for increasing levels of target proteins. With this, we are now well poised to pharmacologically target longevity-associated genes in vivo. In this project, we will: 1) design and test ASOs to modulate the levels of four longevity-associated genes, and 2) test if ASO treatment can extend lifespan and improve healthspan using a mouse model of accelerated aging.
Over the past three decades, genetic studies in model organisms and humans have identified and validated gene mutations and variants that prolong lifespan and enhance healthspan. Together, these findings show that modest changes in expression and/or activity of these genes can have a significant impact on aging and longevity. ASOs are emerging as a promising therapeutic modality, and they enable decreasing the expression of target genes in a specific manner in vivo. Importantly, we developed a novel ASO-based strategy for increasing levels of target proteins. With this, we are now well poised to pharmacologically target longevity-associated genes in vivo. In this project, we will: 1) design and test ASOs to modulate the levels of four longevity-associated genes, and 2) test if ASO treatment can extend lifespan and improve healthspan using a mouse model of accelerated aging.