How does calorie restriction work?

The FoxO transcription factors and metabolic regulation

“…The effects of CR are beginning with an acute phase upon imposition of the diet followed by an adaptive period of several weeks to reach a stable, altered physiological state. A lower body temperature, lower blood glucose and insulin levels, and reduced body fat and weight characterize this altered state [34]. CR regulates Sirt1 expression level and activity.…”

Lifespan extension and increased pumping rate accompany pharyngeal muscle‐specific expression of nfi‐1 in C. elegans

“…Pumping rates decrease with age in wild-type animals and mutations that affect lifespan concomitantly affect pumping rates (Huang et al, 2004). This strong correlation between reduced rates of pharyngeal pumping and accelerated aging appears initially to be paradoxical, because caloric restriction is well know to extend lifespan in several organisms (Koubova and Guarente, 2003). Indeed in C. elegans, some mutations in eat-2 which reduce overall pharyngeal pumping rate can extend adult lifespan.…”

Nutrition, sirtuins and aging

“…In yeast, however, it has been shown that cells respond to reduced glucose in the media by shunting more of the carbon to the TCA cycle to enhance the efficiency of ATP-generation by respiration instead of exploiting glycolysis when glucose offering is not restricted (Lin et al, 2002). Although NAD + -and NADH-levels have not been determined in S. cerevisiae under CR, it was suggested that increased respiration in restricted yeast is associated with an increased NAD + /NADH-ratio in order to account for the activation of Sir2 measured (Koubova and Guarente, 2003). That the NAD + /NADH-ratio can be regulated in a very complex way was shown in the livers of fasted mice where NAD + -levels were increased by fasting and returned to control levels by F F F F Fig.…”

“…In all mammalian species studied so far, caloric restriction (CR) with a reduction of caloric intake from 25% to 60% of that of control animals fed ad libitum, extends the life span, provided that all essential nutrients are present in sufficient amounts in the diet (Koubova and Guarente, 2003). Besides conserving insulinsensitivity, CR blunts sexual maturation and fecundity, which allows long-term survival through energy sparing (Holliday, 1989).…”