Translational geroscience: From invertebrate models to companion animal and human interventions

Abstract

Translational geroscience is an interdisciplinary field descended from basic gerontology that seeks to identify, validate, and clinically apply interventions to maximize healthy, disease-free lifespan. In this review, we describe a research pipeline for the identification and validation of lifespan extending interventions. Beginning in invertebrate model systems, interventions are discovered and then characterized using other invertebrate model systems (evolutionary translation), models of genetic diversity, and disease models. Vertebrate model systems, particularly mice, can then be utilized to validate interventions in mammalian systems. Collaborative, multi-site efforts, like the Interventions Testing Program (ITP), provide a key resource to assess intervention robustness in genetically diverse mice. Mouse disease models provide a tool to understand the broader utility of longevity interventions. Beyond mouse models, we advocate for studies in companion pets. The Dog Aging Project is an exciting example of translating research in dogs, both to develop a model system and to extend their healthy lifespan as a goal in itself. Finally, we discuss proposed and ongoing intervention studies in humans, unmet needs for validating interventions in humans, and speculate on how differences in survival among human populations may influence intervention efficacy. Keywords: Translational geroscience, Healthspan, Longevity, Aging, Rapamycin, Metformin, mTOR, Companion animals