Targeting Metabolic Pathways that Play a Role in Longevity and Cancer

Summary

• Propionate is a short chain fatty acid that is produced by microbes in the gut
• Under normal conditions, propionate is broken down to Syccinyl-CoA
• Dr. Blenis is a leading pioneer in the mTOR space
• Recent work in the Blenis lab has demonstrated that dysregulation of the propionate metabolism pathway results in a build up of methylmalonic acid (MMA) which promotes premature cellular aging
• Their work aims to further elucidate exact mechanisms of action (MoA) that contribute to cancer metastasis and aging in both pathways

Technical Overview

• The Blenis lab has demonstrated that dysregulation of propionate metabolism results in increased serum levels of MMA
• ‘Older’ serum had naturally higher levels of MMA, which provides a direct link between MMA and aging
• Serum MMA can also be impacted by dietary manipulation
• Elevated MMA levels were also linked with increased metastasis, ROS, senescence markers, inflammatory cytokines, fibrosis and immunosuppression
• The labs findings correlated with previous studies that demonstrate that increased MMA levels were correlated with aging, and cardiovascular disease

Market Opportunity

• Very little is known about the root cause of premature aging
• The Blenis lab has demonstrated a direct link between increased serum MMA and aging
• A comprehensive understanding of the role of MMA, it’s dietary causes, and specific functions will help elucidate this complicated area
• The presence of increased MMA may also serve as a novel biomarker for aging and aging related diseases
• Further studies in to elevated MMA levels will shed light on the link between aging, aging related diseases and other chronic metabolic disorders

Partnering Opportunity

Weill Cornell Medicine is seeking an industrial partner with deep domain expertise and a presence in the longevity space to help further elucidate the role of MMA in aging and related disorders

Figure 1: Role of propionate metabolism in aging and propionate metabolism pathway.