In the latest episode of The Genetics Podcast, host and Sano Genetics CEO Patrick Short explores the world of aging research with Dr. Austin Argentieri. Dr. Argentieri is a research fellow at Harvard and the Broad Institute, working in the Analytical and Translational Genetics Unit at Massachusetts General Hospital. With a background that includes a PhD and postdoc from the Big Data Institute at the University of Oxford, Dr. Argentieri focuses on large-scale analyses to understand the genetic, biological, and environmental determinants of human aging and aging-related diseases.
Defining aging: A complex task
The conversation kicks off with Dr. Argentieri tackling the fundamental question of what aging really is. Despite the universal experience of aging, defining it remains surprisingly complex. Dr. Argentieri explains that aging can be viewed through multiple lenses, such as population-level phenomena like life expectancy and mortality risk, or cellular and biological processes involving damage accumulation and genomic instability. He highlights the key cellular hallmarks of aging, which include shortening telomeres, genomic instability, mitochondrial dysfunction, and more.
Landmark research on aging
Patrick and Dr. Argentieri then go into detail on the latter's recent paper published in Nature Medicine. The study focuses on using large-scale population proteomics data to create accurate estimates of biological age across diverse populations. The approach used by his team involves analyzing around 3,000 proteins from blood plasma to predict an individual's chronological age with high accuracy. The divergence between predicted biological age and actual chronological age – known as the "proteomic age gap," provides significant predictive power for mortality, chronic diseases, and various aging phenotypes.
One of the most interesting findings from Dr. Argentieri's research is the strong predictive power of the proteomic age gap. Individuals whose proteomic age is significantly higher or lower than their chronological age are at increased risk for various health outcomes. This includes all major non-cancer causes of death, several cancers, frailty, and biological decline. The study also validates these findings across diverse populations.
Challenges and opportunities in aging research
Dr. Argentieri discusses the implications of his findings for future aging research and therapeutic development. He emphasizes the strategic importance of studying aging to address crucial public health problems such as premature mortality and chronic disease. Additionally, Dr. Argentieri highlights the potential for aging research to inform the development of therapeutics targeting the shared biological pathways underlying multiple chronic diseases.
The conversation also covered the challenges of aging research, particularly the need for better biomarkers and the limitations of current regulatory frameworks. Dr. Argentieri advocates for leveraging large-scale human population data and multi-omics approaches to gain a deeper understanding of aging processes. He also addresses the question of causality, exploring whether the proteins themselves or underlying genetic and environmental factors drive the observed associations with aging and health outcomes.
Summary
This episode of The Genetics Podcast provides a deep dive into fascinating research on aging, offering valuable insights for scientists, healthcare professionals, and anyone interested in the science of aging and longevity.
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