How to evaluate neglectedness and tractability of aging research

Abstract

In the first section, I propose a method to scout for impactful and neglected aging research. This method is comprised of two steps: Identifying what is necessary to achieve LEV and, among what is necessary, identifying what is most neglected. This differs from the Open Philanthropy Project’s approach of ignoring impact derived from Longevity Escape Velocity. A preliminary evaluation, made through including all research on the hallmarks and using lifespan.io’s Rejuvenation Roadmap to identify neglected projects, leads us to identify genomic instability, telomere attrition, epigenetic alterations, deregulated nutrient sensing, loss of proteostasis, and mitochondrial dysfunction as neglected and important areas of research. Other neglected research must be scouted in other equally important areas that have already been identified by Open Philanthropy, such as improving delivery methods and developing better biomarkers. In the second section, I take Open Philanthropy’s and Aubrey de Grey’s stance about considering interventions targeting “aging in general”, such as caloric restriction or metformin, as having low tractability and impact. What remains after this first skimming is translational research focusing on the hallmarks, basic non-translational research, and enabling research, such as developing new tools and delivery methods. When prioritizing inside these areas, tractability should be considered only after having first considered neglectedness while trying to maximize scope by looking at research that is necessary for reaching LEV. Otherwise, a relatively small gain in tractability would sacrifice an extreme amount of impact and neglectedness. This is true because the hardest problems in the field are often the most neglected, but if they are necessary for achieving LEV, they will be solved later, and by accelerating them, we can impact the expected date of LEV the most.