The role of Hsp70 in oxi-inflamm-aging and its use as a potential biomarker of lifespan.

ABSTRACT

The heat-shock protein 70 (HSPA1A or Hsp70) acts as a cellular defense mechanism its expression being induced under stressful conditions. Aging has been related to an impairment in this induction. However, an extended longevity has been associated with its increased expression. According to the oxidation-inflammation theory of aging, chronic oxidative stress and inflammatory stress situations (with higher levels of oxidant and inflammatory compounds and lower antioxidant and anti-inflammatory defenses) are the basis of the age-related alterations of body cells. Since oxidation and inflammation are interlinked processes, and Hsp70 has been shown to confer protection against the harmful effects of oxidative stress as well as modulating the inflammatory status, it could play a role as a regulator of the rate of aging. This role may be different in mitotic and post-mitotic tissues due to the differences in their age-related mechanisms of response, such as apoptosis. Mechanisms affected by Hsp70 that can interfere with the deleterious effects of excessive oxidative stress and chronic low-grade inflammation and that are closely related to the aging process have been detailed. In addition, the potential use of the basal levels (with their differences in post-mitotic and mitotic tissues), the inducible levels, as well as the extracellular levels of Hsp70 as possible biomarkers of the rate of aging and lifespan, have also been discussed.