Hallmarks of aging: A user's guide for comparative biologists

Since the first description of a set of characteristics of aging as so-called hallmarks or pillars in 2013/2014, these characteristics have served as guideposts for the research in aging biology. They have been examined in a range of contexts, across tissues, in response to disease conditions or environmental factors, and served as a benchmark for various anti-aging interventions. While the hallmarks of aging were intended to capture generalizable characteristics of aging, they are derived mostly from studies of rodents and humans. Comparative studies of aging including species from across the animal tree of life have great promise to reveal new insights into the mechanistic foundations of aging, as there is a great diversity in lifespan and age-associated physiological changes. However, it is unclear how well the defined hallmarks of aging apply across diverse species. Here, we review each of the twelve hallmarks of aging defined by Lopez-Otin in 2023 with respect to the availability of data from diverse species. We evaluate the current methods used to assess these hallmarks for their potential to be adapted for comparative studies. Not unexpectedly, we find that the data supporting the described hallmarks of aging are restricted mostly to humans and a few model systems and that no data are available for many animal clades. Similarly, not all hallmarks can be easily assessed in diverse species. However, for at least half of the hallmarks, there are methods available today that can be employed to fill this gap in knowledge, suggesting that these studies can be prioritized while methods are developed for comparative study of the remaining hallmarks.