title: Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is Associated with Increased Oxidative Stress.
abstract: Age-associated declines in protein homeostasis mechanisms ("proteostasis") are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = -0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = -0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: -0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain.
authors: Departments of Neurology, Beaumont Hospital-Royal Oak, Beaumont Health, Royal Oak MI, USA.
authors: David A
authors: DA
authors: Loeffler
authors: Departments of Neurology, Beaumont Hospital-Royal Oak, Beaumont Health, Royal Oak MI, USA.
authors: Andrea C
authors: AC
authors: Klaver
authors: Departments of Biostatistics, Beaumont Hospital-Royal Oak, Beaumont Health, Royal Oak MI, USA.
authors: Mary P
authors: MP
authors: Coffey
authors: Department of Neurology, St. Olav's Hospital Trondheim, Norway.
authors: Jan O
authors: JO
authors: Aasly
authors: Department of Neurology, Henry Ford West Bloomfield Hospital, West Bloomfield TownshipMI, USA; Department of Neurology, Wayne State University School of Medicine, DetroitMI, USA.
authors: Peter A
authors: PA
authors: LeWitt
keywords: 8-hydroxydeoxyguanosine; 8-isoprostane; HSPA8; aging; cerebrospinal fluid; oxidative stress