Circulating Heat Shock Protein 70 in Health, Aging and Disease

Serum Hsp70, Interleukin (IL) -10, IL-6 and Tumor Necrosis Factor (TNF) alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years) and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years). In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L) showed significantly (p = 0.007) higher Hsp70 values; and Hsp70 correlated positively (p < 0.001) with IL-6 and CRP, but not with TNF-alpha or IL-10. A significant association was also noted between Hsp70 levels and the degree of dependency and cognitive decline in geriatric patients.The present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients.Heat shock proteins (Hsp) are primarily expressed as intracellular proteins that exhibit a range of fundamental roles necessary for cell survival. Intracellular functions of Hsp include both specific biological actions that are linked to a particular Hsp and more general chaperone activities that result in the stabilisation and protection of newly synthesised proteins, targeting ultimately damaged proteins for degradation and transportation of proteins to their sites of activity [1]. Although research has mainly focused on intracellular Hsp, it is now obvious that Hsp [2] as well as Hsp receptors [3] are expressed on the cell surface and that Hsp are circulating in the blood [4]. Hsp can be secreted by viable cells, such as peripheral blood mononuclear cells which are thought to contribute significantly to circulating Hsp70 [5,6]. Extracellular Hsp have been reported to exhibit beneficial properties, such as enhancing the survival of cultured