Insulin sensitivity, antioxidants, and memory function in aging

Insulin resistance has been associated with dysfunction of mitochondria. Iwabu et al have an article showing that this may be transduced at the molecular level by the adiponectin receptor 1 (AdipoR1). From the abstract:

Suppression of AdipoR1 also resulted in decreased PGC-1α expression and deacetylation, decreased mitochondrial content and enzymes, decreased oxidative type I myofibres, and decreased oxidative stress-detoxifying enzymes in skeletal muscle, which were associated with insulin resistance and decreased exercise endurance. Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes.

This short essay explains the age-dependent differences in cognitive changes following caloric restriction via insulin sensitivity. People age 50 +  have benefits in recall (~ 30% more words remembered after 30 mins) following CR while people ages 25 – 45 see no significant benefits. This makes sense if CR improves insulin sensitivity, leading to increased protection from oxidative stress (more evidence for which Iwabu et al provide above), leading to less neural damage (antioxidants have much increased neuroprotective effects in older cohorts), leading to improved memory.

Reference

Iwabu M, et al. 2010 Adiponectin and AdipoR1 regulate PGC-1α  and mitochondria by Ca2+ and AMPK/SIRT1. doi:10.1038/nature08991