Once again the booming literature on calorie restriction (CR) has bested me, and I’ve fallen hopelessly behind. Therefore, without comment, I’ll just run through the last month’s abstracts, with a smattering of brief commentary here and there. Each paper deserves its own entry, but we’re just going to have to make do with this. Quoted passages are all abstract excerpts.

The Nrf2 pathway: Mechanisms Underlying Caloric Restriction and Lifespan Regulation: Implications for Vascular Aging, Ungvari et al.:

We propose that caloric restriction increases bioavailability of NO, decreases vascular reactive oxygen species generation, activates the Nrf2/antioxidant response element pathway, inducing reactive oxygen species detoxification systems, exerts antiinflammatory effects, and, thereby, suppresses initiation/progression of vascular disease that accompany aging.

More on Nrf2 and aging here and here.

Protein vs. sugar in insulin signaling: Opposing Effects of Dietary Protein and Sugar Regulate a Transcriptional Target of Drosophila Insulin-like Peptide Signaling, Buch et al.

Through microarray analysis of flies in which the insulin-producing cells (IPCs) were ablated, we identified a target gene, target of brain insulin (tobi), that encodes an evolutionarily conserved -glucosidase. Flies with lowered tobi levels are viable, whereas tobi overexpression causes severe growth defects and a decrease in body glycogen. Interestingly, tobi expression is increased by dietary protein and decreased by dietary sugar.

Inactivity and inflammation: Calorie restriction modulates inactivity-induced changes in the inflammatory markers CRP and PTX3, Busutti et al.:

Calorie restriction prevents the inflammatory response induced by 14 days of bed rest. We suggest an inverse regulation of CRP and PTX3 in response to changes in energy balance.

*** This was a human study.

“Nutritional emphysema”: Effect of Severe Calorie Restriction on the Lung in Two Strains of Mice, Bishai and Mitzner:

Although the baseline mechanics and alveolar size were quantitatively different in the two strains, both strains showed similar qualitative changes during the starvation and refeeding periods. Thus, in two strains of mice with genetically determined differences in alveolar size neither the mechanics nor the histology show any evidence of emphysema-like changes with this severe caloric insult.

SIRT1 stabilization: Regulation of SIRT1 protein levels by nutrient availability, Kanfi et al.:

We show here that levels of SIRT1 increased in response to nutrient deprivation in cultured cells, and in multiple tissues of mice after fasting. The increase in SIRT1 levels was due to stabilization of SIRT1 protein, and not an increase in SIRT1 mRNA. In addition, p53 negatively regulated SIRT1 levels under normal growth conditions and is also required for the elevation of SIRT1 under limited nutrient conditions.

Protein modification in the heart: Aging and dietary restriction effects on ubiquitination, sumoylation, and the proteasome in the heart, Li et al.:

Cumulatively, our data indicate that DR has many beneficial effects towards the UPP [ubiquitin-proteasome pathway] in the heart, and suggests that a preservation of the UPP may be a potential mechanism by which DR mediates beneficial effects on the cardiovascular system.

Males vs. females, round 1: The brain: Conserved and Differential Effects of Dietary Energy Intake on the Hippocampal Transcriptomes of Females and Males, Martin et al.:

Genes involved in energy metabolism, oxidative stress responses and cell death were affected by the HFG diet in both males and females. The gender-specific molecular genetic responses of hippocampal cells to variations in dietary energy intake identified in this study may mediate differential behavioral responses of males and females to differences in energy availability.

Males vs, females, round 2: The gonad: Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary, Sharov et al.:

CR-mediated reversal of age-associated gene expression changes, reported in somatic organs previously, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis.

Whew. OK, have a great weekend, everyone.