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Influence of Normal Aging on Brain Autophagy: A Complex Scenario
1Beaumont Research Institute, Department of Neurology, Beaumont Health, Royal Oak, MI, United States.
Frontiers in Aging Neuroscience
|March 28, 2019
Summary
Brain autophagy, crucial for clearing misfolded proteins linked to neurodegenerative diseases, may decline with age. Further research is needed, especially in humans, to confirm this age-associated decline and explore interventions.
Area of Science:
- Neuroscience
- Aging Research
- Cellular Biology
Background:
- Misfolded proteins accumulate in neurodegenerative disorders like Alzheimer's and Parkinson's.
- Aging is a significant risk factor for these diseases, suggesting age-related decline in protein clearance mechanisms.
- The brain's ubiquitin-proteasome system and autophagy-lysosomal pathway are key protein clearance systems, but their age-related function in the brain remains unclear.
Purpose of the Study:
- To review and examine age-associated changes in macroautophagy and chaperone-mediated autophagy (CMA) within the central nervous system (CNS).
- To synthesize current literature on the decline of brain autophagy with aging and its implications for neurodegeneration.
Main Methods:
- Literature review of studies investigating age-related changes in brain autophagy.
- Analysis of markers for macroautophagy (Beclin 1, LC3-II, LC3-II/LC3-I ratio) and CMA (lamp2a, HSPA8/hsc70).
- Examination of gene expression analyses and cerebrospinal fluid concentrations in human and animal models.
Main Results:
- Gene expression analyses suggest age-related downregulation of macroautophagy in the human brain.
- No studies found on age-related CMA changes in the human brain, though HSPA8 decreased with age in cerebrospinal fluid.
- Most animal studies show age-related declines in brain macroautophagy; CMA results are conflicting, but generally decrease with age in other systems.
Conclusions:
- Indirect evidence suggests brain autophagy may decline with normal aging, but this requires further investigation, particularly in humans.
- Challenges in measuring brain autophagic activity include model variability and limitations with postmortem specimens.
- If brain autophagy declines with age, interventions could potentially reduce the risk of age-related neurodegenerative disorders.
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