The role of cellular senescence in aging through the prism of Koch-like criteria

Since Hayflick's discovery of cellular senescence (CS), a great volume of knowledge in the field has been accumulated and intensively discussed. Here, we attempted to organize the evidence “for” and “against” the hypothesized causal role of CS in aging. For that purpose, we utilized robust Koch-like logical criteria, based on the assumption that some quantitative relationships between the accumulation of senescent cells and aging rate should exist. If so, it could be expected that (i) the “CS load” would be greater in the premature aging phenotype and lesser in longevity phenotype; (ii) CS would promote age-related diseases, and (iii) the interventions that modulate the levels of senescent cells should also modulate health/lifespan. The analysis shows that CS can be considered a causal factor of aging and an important player in various age-related diseases, though its contribution may greatly vary across species. While the relative impact of senescent cells to aging could overall be rather limited and their elimination is hardly expected to be the “fountain of youth”, the potential benefits of the senolytic strategy seems a promising option in combating age-related diseases and extending healthspan.