Age-related declines in cognitive fitness are associated with a reduction in autophagy, an intracellular lysosomal catabolic process that regulates protein homeostasis and organelle turnover.
Senescent microglia are present in greater numbers in the brains of patients with neurodegenerative conditions.
Cellular senescence plays a direct role in chronic and age-related diseases and conditions, such as diabetes, atherosclerosis, neurovascular dysfunction, frailty, and dementias. Accumulation of senescent cells with aging contributes to multiple, age-related comorbidities that are frequently accompanied by neurodegenerative diseases, especially AD.
Autophagy is an essential catabolic process frequently failing in neurodegeneration.
Autophagy is an essential cellular antioxidant pathway in neurodegenerative disease.
Autophagy not only promotes waste clearance in the brain, but also alters cognitive abilities by changing the efficiency of the intracellular transportation system.
Autophagy provides better regulation of neuron calcium levels.
There is a role for autophagy in the clearance of extracellular Aβ fibrils by microglia.
…autophagy is critical for neuronal survival. Recent work in the field of Alzheimer’s disease has provided molecular and cellular evidence that links diminished autophagy to the pathogenesis of AD.
Examination of a large set of human brain samples revealed a striking relationship between Alzheimer’s disease (AD) status and isomerization of aspartic acid in a peptide from tau. Relative to controls, a surprising increase in isomer abundance was found in both autosomal dominant and sporadic AD samples. To explore potential mechanisms that might account for these observations, quantitative analysis of proteins related to isomerization repair and autophagy was performed. Differences consistent with reduced autophagic flux in AD-related samples relative to controls were found for numerous proteins, including most notably p62, a recognized indicator of autophagic inhibition.
The hippocampus has a distinct circadian rhythm of autophagy that can be altered by sleep fragmentation.
Obesity causes a massive increase in senescent cells. Exercise can reduce the burden of senescent cells.
Chronic sleep deprivation impairs learning and memory, autophagy and neuronal apoptosis in mice.
Autophagy is up-regulated by calorie restriction, via neuropeptide Y.
Short-term fasting leads to a dramatic upregulation in neuronal autophagy.
Melatonin promotes neuronal autophagy.
Oleuropein aglycone (from olives/olive oil) may benefit Alzheimer’s disease by promoting autophagy.
Sulforaphane induces autophagy through extracellular signal-regulated kinase activation in neuronal cells. Pretreatment with NAC (N-acetyl-l-cysteine), a well-known antioxidant, completely blocked this autophagy effect. Sulforaphane of cruciferous vegetables enhanced autophagy flux led to the protection effects against prion-mediated neurotoxicity, which was regulated by AMPK signaling pathways in human neuron cells.
Based on literature data, it is suggested that physical exercise can induce autophagy in the aged brain via multiple mechanisms.
Stimulating mitophagy and optimizing mitochondrial function through exercise may forestall the neurodegenerative process of AD.•
A high dose of Urolithin A positively impacts exercise-performance measures. An increase in
mitophagy proteins in human skeletal muscle observed in parallel. Supplementation is safe and increases circulating levels of Urolithin A.
- Mitochondrial and cellular health
- Age-related conditions
- Metabolic function
- Gastrointestyinal homeostasis
- Acute diseases
EGCG from green tea promotes neuronal autophagy.
Senolytics including quercetin and fisetin have been shown effective at decreasing senescent cells in humans.
Ketosis may promote brain macroautophagy by activating Sirt1 and hypoxia-inducible factor-1. Ketones may up-regulate neuronal autophagy as a rational strategy for prevention of neurodegenerative disorders; elimination of damaged mitochondria that overproduce superoxide, as well as clearance of protein aggregates that mediate neurodegeneration. Many people can go into ketosis between meals. So run on an empty stomach, especially after doing resistance training.