In Search of Robust Biomarkers to Connect Cellular Senescence to Age-Related Chronic Inflammation
Senescent cells accumulate with age, and actively secrete pro-inflammatory signals. The present understanding of senescent cell biochemistry and animal studies of senescent cell clearance strongly suggest that senescent cells in aged tissues provide a major contribution to the characteristic chronic inflammation of old age, disruptive to tissue structure and function. As researchers here note, finding biomarkers to quantify this contribution in a usefully robust and specific way is a work in progress, however. While one might think that the medical field could forge ahead with therapies targeting senescent cells for clearance, based on being able to evidently reverse age-related pathology in animal studies, in practice regulators place a strong emphasis on the availability of simple biomarkers that can measure the direct engagement of a drug with its target, not just indirect outcomes. Drugs that lack such biomarkers will struggle to progress though the regulatory system, and thus creating these biomarkers is a major concern for researchers and companies.
Cellular senescence is the process in which cells lose their ability to proliferate irreversibly. While the process is needed for performing different functions, accumulation of senescent cells over time leads to the secretion of senescence-associated secretory phenotype (SASP). Senescence and SASP have now been known, defined and quantified in the last couple of decades. Both senescence and inflammaging are known to contribute towards several age-related diseases (ARDs), with inflammaging being a more recent concept than the former. They appear bi-directional in their cause and effects with respect to ARDs, resulting in immunosenescence, which is the age-related decline in the functioning of the immune system, but senescence is currently more quantifiable due to specific markers and known senescent cellular features.
With the increasing interest in the field, several scientists and research groups have contributed to the growing body of evidence towards cellular senescence and inflammaging in ARDs. Existing evidence indicates that senescence might be the key to tracking diseases (and thus targeting senescence for treatment), healthy aging and longevity; however, this knowledge is yet to be translated to the 'bedside' for clinical applications. This review aims to outline and simplify our current understanding of the complex links between aging, senescence and inflammaging in ARDs, classify and list the biomarkers of aging, and discuss the knowns and the unknowns of the field.