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Related Experiment Video

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Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry
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Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is Associated with Increased Oxidative

David A Loeffler1, Andrea C Klaver1, Mary P Coffey2

  • 1Departments of Neurology, Beaumont Hospital-Royal Oak, Beaumont Health, Royal Oak MI, USA.

Frontiers in Aging Neuroscience
|August 11, 2016
PubMed
Summary

Healthy aging is linked to decreased heat shock 70-kDa protein 8 (HSPA8) in cerebrospinal fluid, potentially due to increased oxidative stress. 8-hydroxy-2'-deoxyguanosine (8-OHdG) may be a sensitive marker for this stress.

Keywords:
8-hydroxydeoxyguanosine8-isoprostaneHSPA8agingcerebrospinal fluidoxidative stress

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Gerontology

Background:

  • Age-associated declines in proteostasis contribute to neurodegeneration.
  • Oxidative stress increases with aging and activates proteostatic mechanisms like chaperone-mediated autophagy.

Purpose of the Study:

  • Investigate age-related changes in cerebrospinal fluid (CSF) heat shock 70-kDa protein 8 (HSPA8) concentrations.
  • Examine associations between HSPA8, oxidative stress markers (8-hydroxy-2 -deoxyguanosine [8-OHdG], 8-isoprostane), and total antioxidant capacity (TAC) in healthy aging.

Main Methods:

  • Correlational analysis of age, HSPA8, 8-OHdG, 8-isoprostane, and TAC in CSF samples from 34 healthy subjects (20-75 years).

Main Results:

  • Age negatively correlated with HSPA8 (ρ = -0.47; p = 0.005).
  • Age positively correlated with 8-OHdG (ρ = 0.61; p = 0.0001), indicating increased oxidative stress.
  • HSPA8 negatively correlated with 8-OHdG (ρ = -0.58; p = 0.0004).
  • Weak associations were found between age/HSPA8 and 8-isoprostane/TAC.

Conclusions:

  • CSF HSPA8 may decrease during healthy aging, possibly due to increased oxidative stress.
  • 8-OHdG appears more sensitive than 8-isoprostane for measuring oxidative stress in CSF.
  • Further research with larger cohorts is needed to validate findings and explore brain HSPA8 changes.