Fight Aging!

Calorie restriction with optimal nutrition is the practice of eating fewer calories, cutting perhaps a third of those in a normal healthy diet, while still obtaining optimal amounts of essential micronutrients. Calorie restriction reliably extends healthy and maximum life spans by up to 40% in short-lived mammals such as mice and rats. It slows aging and extends life in near all species for which rigorous life span studies have been carried out, in fact. The calorie restriction response seems almost universal in the animal kingdom, with many of the identified mechanisms similar or the same in widely separated species. This is a phenomenon that probably originates a long way back in evolutionary time, in other words. When it comes to longer-lived species such as primates, including we humans, the only truly comprehensive and rigorous data presently to hand covers short-term reactions to calorie restriction, however. It takes a long time to run a life span study for humans or even for our neighboring primates: two calorie restriction studies in rhesus macaques have been running for decades now, and there is some debate over whether the study design has led to data that is too flawed to be useful.

The bottom line question: does calorie restriction extend life in humans? The present consensus in the scientific community is that the answer is probably yes, but not by anywhere near the same degree as in short-lived mammals. From an evolutionary perspective, the calorie restriction response arises because it improves survival in the face of seasonal famine. A season is a large portion of a mouse life span, but not so much time for a human, and thus only the mouse evolves a dramatic plasticity of aging and longevity in response to circumstances. Nonetheless, the cataloged health benefits of calorie restriction in humans are impressive and very similar to those observed in mice. There is no presently available medical technology that can grant the same degree of benefits to a basically healthy individual, when looking at important measures such as blood pressure, resistance to common age-related diseases, and so forth. It is true that you can't reliably live to age 90 and beyond in good health via any lifestyle choice, calorie restriction included, but in the present era of rapid progress in medicine, every extra year that you can win for yourself counts. The line in the sand to separate those who die too soon to benefit from near future rejuvenation technologies and those who just make it will be narrow indeed.

So give a little thought to trying calorie restriction. What do you have to lose? Here are a couple of items pulled from the stack, pointers to recent research into calorie restriction and the health benefits it produces. These are all fairly typical of the field, meaning a narrow investigation of one small aspect of biochemistry, and a confirmation that calorie restriction improves matters by slowing or delaying age-related changes:

SAGE Review: New insights into calorie restriction and its effects on sarcopenia and aging

Researchers reported that calorie restriction in rats has an age-dependent protective effect on age-related muscle loss by improving skeletal muscle metabolism in rats. The authors fed young (4 month) and middle-aged (16 month) rats one of two diets - either a normal diet, ad libitum (AL), or a restricted diet, 40% calorie restriction (CR), for a total of 14 weeks. They found that normalized muscle weight (muscle weight divided by body weight) was lower in normal, AL-fed, middle-aged rats compared to young rats. However, when the two age groups were fed the CR diet, skeletal muscle in middle-aged rats was protected from expected age-related degeneration and muscle mass was comparable to levels of young rats fed the AL diet. Interestingly, CR had a negative effect on normalized muscle weight in young mice and caused a decrease in muscle mass.

It seems that CR has an age-dependent beneficial effect on skeletal muscle mass in rats and can reprogram skeletal muscle metabolism to function at levels that resemble those of young rats fed a normal diet. A more applicable question arising from this study is whether CR can counteract muscle degeneration in middle-aged or elderly humans. This study suggests that middle-aged humans could potentially benefit from a CR diet with respect to preventing muscle loss. Conducting a similar experiment in humans will be a much larger endeavor, however, scientists can use what we learn from these rat studies and other model organisms to better understand metabolic pathways that go awry with aging. Ultimately, understanding the mechanisms behind the beneficial effects of CR and how they influence muscle loss during aging will open the doors for the development of therapies to prevent or treat aging-related diseases.

Subacute calorie restriction and rapamycin discordantly alter mouse liver proteome homeostasis and reverse aging effects

Calorie restriction (CR) and rapamycin (RP) extend lifespan and improve health across model organisms. Both treatments inhibit mammalian target of rapamycin (mTOR) signaling, a conserved longevity pathway and a key regulator of protein homeostasis, yet their effects on proteome homeostasis are relatively unknown. To comprehensively study the effects of aging, CR, and RP on protein homeostasis, we performed the first simultaneous measurement of mRNA translation, protein turnover, and abundance in livers of young (3 month) and old (25 month) mice subjected to 10-week RP or 40% CR.

We observed 35-60% increased protein half-lives after CR and 15% increased half-lives after RP compared to age-matched controls. Surprisingly, the effects of RP and CR on protein turnover and abundance differed greatly between canonical pathways. CR most closely recapitulated the young phenotype in the top pathways. Polysome profiles indicated that CR reduced polysome loading while RP increased polysome loading in young and old mice, suggesting distinct mechanisms of reduced protein synthesis. CR and RP both attenuated protein oxidative damage. Our findings collectively suggest that CR and RP extend lifespan in part through the reduction of protein synthetic burden and damage and a concomitant increase in protein quality. However, these results challenge the notion that RP is a faithful CR mimetic and highlight mechanistic differences between the two interventions.

Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain

Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging.