How to live for centuries: common denominators of organisms with exceptional longevity

Organisms vary in their lifespan. Understanding this variation may help us live healthier and longer. Here, we focus on species living twice as long as humans, or more. Out of the 101 multicellular species with a maximum lifespan of 250+ years, 11 are animals and 90 are plants. We surveyed the genetic, transcriptional, proteomic, metabolomic, regeneration-, stress-, and cancer-related components of intraspecific and interspecific lifespan variation, across these species. We examined whether the mechanisms regulating intraspecific lifespan variation across these species are the same or different from mechanisms regulating interspecific lifespan variation. We identified several similarities: both types of variation include mechanisms related to DNA maintenance, stemness, and stress management. Such mechanisms are also typical of early developmental stages and germ cells. Nonetheless, caution should be exercised when attempting to draw robust conclusions based on available data, given the lack of in-depth molecular studies on the healthspan and lifespan across thousands of individuals and species, the methodological variation across published studies, and our partial understanding of the interplay between physiology and the environment across species.