Caloric restriction and the aging process: a critique

Abstract

The main objective of this review is to provide an appraisal of the current status of the relationship between energy intake and the life span of animals. The concept, that a reduction in food intake, or caloric restriction (CR), retards the aging process, delays the age-associated decline in physiological fitness and extends the life span of organisms of diverse phylogenetic groups, is one of the leading paradigms in gerontology. However, emerging evidence disputes some of the primary tenets of this conception. One disparity is that the CR-related increase in longevity is not universal and may not even be shared among different strains of the same species. A further misgiving is that the control animals, fed ad-libitum (AL), become overweight, prone to early onset of diseases and death, and thus may not be the ideal control animals for studies concerned with comparisons of longevity. Re-examination of body weight and longevity data from a study involving over 60,000 mice and rats, conducted by a National Institute on Aging-sponsored project, suggests that CR-related increase in life span of specific genotypes is directly related to the gain in body weight under the AL feeding regimen. Additionally, CR in mammals and “dietary restriction” in organisms, such as Drosophila, are dissimilar phenomena, albeit they are often presented to be the very same. The latter involves a reduction in yeast rather than caloric intake, which is inconsistent with the notion of a common, conserved mechanism of CR action in different species. Although specific mechanisms by which CR affects longevity are not well understood, existing evidence supports the view that CR increases the life span of those particular genotypes that develop energy imbalance due to AL feeding. In such groups, CR lowers body temperature, rate of metabolism and oxidant production, and retards the age-related pro-oxidizing shift in the redox state.

On the complex relationship between energy expenditure and longevity: Reconciling the contradictory empirical results with a simple theoretical model

“…We assume that when the mass-specific damage level reaches a threshold, animals die, i.e., D(LS) = C, where LS is the lifespan. The existence of thresholds of oxidative damage for losses of functions or mortality has also been assumed by Sohal and his colleagues (Sohal and Forster, 2014;Sohal and Orr, 2012). We assume that the threshold C is a constant within a taxon.…”

“…We combine our Assumption 3 (lifespan is reached when damage reaches a threshold) and the argument from Sohal and Forster (2014) to answer this question. Attempting to explain why the relatively high DNA damage in OGG1-null mice showed no effect on survival, Sohal and Forster (2014) suggested that this is because "high threshold levels of DNA and protein oxidative damage are required for manifest losses in function".…”

Fox transcription factors: from development to disease

“…First, in some mouse strains, life expectancy was actually shortened in cohorts with calorie restriction (Liao et al, 2010;Swindell, 2012). Second, ad libitum fed controls might not be an ideal comparison for rodents with calorie restriction; ad libitum access to normal chow leads to weight gain and associated detrimental health effects (Sohal and Forster, 2014). Mixed results have also been reported for non-human primates (Colman et al, 2009;Bodkin et al, 2003;Mattison et al, 2012), and studies correlating calorie restriction and longevity are hard to perform accurately in humans and thus far have been inconclusive (Heilbronn and Ravussin, 2003).…”

Calorie Restriction An Approach towards Obesity Management

“…This placed the beginning to bring up research on how to normalise findings on metabolic rate for differences in body size. Sohal and Forster [27] highlighted in their recent review that the effect of CR on metabolic rate is not brief but long lasting.…”