Why calorie restriction would work for human longevity

Abstract

Experimentally imposed calorie restriction (CR) is shown to result in the most reproducible endpoint of lifespan extension in all animals models tested. In this presentation, the question of CR's effect on human longevity is reviewed by discussing data pertinent to the putative efficacy of CR on humans. Arguments are presented in support of this possibility based on CR's unique abilities to retard biological functional declines and to deter pathological processes, both of which are major targets of deleterious oxidative stress. To delineate the cellular and molecular mechanisms of CR's efficacy on human longevity, this review elaborates on the modulation of CR on the inflammatory process, a common risk factor for many chronic diseases. Discussions also include evidence from human data on the effect of CR in the loss of body weight, known to suppress inflammatory cytokines, subsequently leading to the reduction of chronic diseases known to compromise the functional longevity of humans.

Calorie restriction: Decelerating mTOR-driven aging from cells to organisms (including humans)

“…Some evidence that CR must prolong life span in humans was recently reviewed. 6,13,[97][98][99][100] cell culture and in the organism. [75][76][77] For example, the TOR activity was evaluated in vivo in skeletal muscle of 24 healthy human volunteers.…”

Oxidative Modification of Proteins: Age-Related Changes

“…2 The carbonyl content of proteins, which is an indicator of protein oxidation, increases exponentially as a function of age [30] . 3 Dietary restriction without malnutrition, which reduces production of ROS, also increases the mean and maximum life span of animals [37,38] .…”

“…Studies on the antiaging effect of CR on the age-related upregulation of redox-sensitive factors, such as nuclear factor-kappa B, transcription factor AP-1, and hypoxia-inducible factor 1, have been carried out [38,107,108] .…”

Modulation of white adipose tissue proteome by aging and calorie restriction

“…In rodents, 30-40% reduction in caloric intake has been shown to extend maximum life span 30-50% and reduce numerous pathological phenotypes, including type II diabetes (Astrup, 2001), neurodegenerative disorders (Patel et al, 2005), oxidative stress (Yu, 2006) and inflammation (Kalani et al, 2006). Although attenuation of oxidative stress and reduction of glycemia and insulinemia have been proposed to be involved in the actions of CR, the exact underlying mechanism and the main target tissue involved in the benefits of this intervention are still debatable (Sohal & Weindruch, 1996).…”