Super Agers: An Evidence-Based Approach to Longevity

Topol surveys what he calls the modern longevity circus, or the hype and the legitimate science surrounding efforts to extend lifespan and health span. He notes the rise of hundreds of longevity clinics, expensive anti-aging regimens, and high-profile entrepreneurs investing heavily in biotechnology companies. While much of this activity is driven by exaggerated claims and unproven therapies, serious scientific progress has also been made in understanding the biology of aging.

Topol outlines the difference between life expectancy (LE) and health-adjusted life expectancy (HALE): While people are living longer, the years gained are often accompanied by chronic illness, limiting HALE. To close the gap between LE and HALE, slowing whole-body aging rather than targeting individual diseases will be necessary. Researchers debate whether there is a biological upper limit to human lifespan, with arguments ranging from cellular division constraints to systemic wear and tear.

The biology of aging is characterized by 12 hallmarks, expanded from nine in recent years to include chronic inflammation, the gut microbiome, and cellular waste removal. These interconnected processes, such as genomic instability, telomere shortening, proteostasis loss, and stem cell exhaustion, represent potential targets for intervention. Genetics play a role in longevity, but are estimated to account for only a small portion of lifespan variance.