Abstract
BackgroundHeat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters.ResultsSerum 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.ConclusionsThe 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.
Highlights
Heat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects
In this study, we provide new evidence regarding the age-related differences in circulating Hsp70 levels by comparing 190 elderly persons - stratified for clinical profile - with 100 healthy young controls
The mechanisms underlying the age-related effects on circulating Hsp70 are largely unknown, evidence from in vitro studies suggest that age-related differences in the production of intracellular Hsp70 might reflect the limited transcription of the heat shock genes, which has been confirmed as due to reduced activation and binding of the HSF 1 to the HSE and/or an impairment in the post-translational processing of Hsp70 mRNA, resulting in its impaired nuclear transport [4]
Summary
Heat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. We have previously drawn attention to the higher basal levels of Hsp that are found in unstimulated lymphocytes and monocytes of the elderly compared to young healthy volunteers [16]. We reported previously that inflammation in elderly patients resulted in higher circulating Hsp levels [17,19,20]. It remains unclear whether the concentrations of circulating Hsp change as a person gets older, and whether there is any relationship with the subclinical inflammatory condition that accompanies normal aging. Since aging results in an increased prevalence of various diseases that might interfere with Hsp production, we investigated a group of geriatric patients
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