Modeling Aging and Age-Related Disease with Human Stem Cells

Humans are exceptionally long-lived in comparison to other primates, with a projected maximum lifespan of ~115 years. This extreme longevity presents unique challenges to many of the post-mitotic cells that compose our bodies and makes us highly susceptible to age-associated diseases (AADs) such as cancer, diabetes, and various neurodegenerative diseases. Though many different research approaches are being pursued to better understand the process of aging as well as to assess the interphase between aging and disease, there is no unifying concept that fully tackles the complexity of the biology of aging. As the global mean population age continues to rapidly increase, these diseases constitute an enormous burden on societies’ health care systems. Further complicating the issue is the fact that many AADs lack effective therapies, due in large part to failed drug discovery efforts in recent years. These shortfalls are united by the common thread that our basic understanding of AADs has been limited by our ability to successfully generate workable human models in the laboratory. While the animal models we rely on so heavily to model AADs are useful tools to grasp generalized concepts related to age and the genes involved in age-related decline, they might not always appropriately reflect the specific mechanisms of human disease. To bridge this knowledge gap and better understand the process of aging in humans and its contribution to disease, we must develop better models that are more reflective of our biology in the hopes that we can translate our findings to new therapeutic advance. This presentation will address the key features of aging that appear to drive neurodegeneration, compare the iPSC and direct conversion approaches for next-generation human cellular modeling, and discuss the extent to which iNs reflect aged neurons.