Evaluating the Effects of Calorie Restriction on Biomarkers of Human Health and Aging

This very readable open access paper is illustrative of the sort of work presently taking place to try to put some numbers to the effects of calorie restriction in humans, though note that these researchers are very focused on the harms caused by excess visceral fat tissue rather than other possible mechanisms. When it comes to the practice of calorie restriction there is plenty of data for the short term benefits to health, and via existing epidemiological studies that can be extrapolated the longer term reduced risk of age-related disease, but there is very little data that sheds light on the degree to which calorie restriction should be expected to extend human life expectancy. We know it won't do as much for human life span as it does for mice, as human life expectancy is much less plastic in response to circumstances. If eating less produced a life span half as long again in our species, as it can in mice, we'd certainly know about it by now. One of the challenges for researchers in the field is to explain the reasons for this difference, given that the short term changes in mice and humans resulting from calorie restriction are in fact very similar.

Aging and wrong lifestyle choices, including inadequate dietary patterns, increase the risk of developing several diseases such as obesity and its-related chronic degenerative diseases. Interestingly, the aging program can be accelerated by obesity. It is thus likely that obesity reduces life- and health span and plays a predominant role in the onset of age-related diseases. In fact, the prevalence of obesity is globally increasing in populations and has become a burden for healthcare systems. Several studies suggest that dietary restriction (DR) regimens (e.g. intermittent fasting, calorie restriction, low calorie diet) reverse obesity and improve health in human by promoting the same molecular and metabolic adaptations that have been shown in animal models of longevity. In particular, DR in humans ameliorates several metabolic and hormonal factors that are implicated in the pathogenesis of an array of age-associated chronic metabolic diseases.

At present it is difficult to evaluate the effectiveness of DR on lifespan in humans, so that several works proposed predictive non-invasive biomarkers to evaluate the geroprotective role of DR. However, a miscellaneous of biomarkers is investigated in human intervention studies limiting the statistical robustness of the data. Whether a "biomarker-based" approach could be suitable for evaluating the effectiveness of DR still remains a matter of debate. Precision medicine is a medical model that proposes the customization of healthcare, with the identification of predictors that can help to find the effectiveness of health-promoting dietary interventions. Biomarkers represent potentially predictive tools for precision medicine but, although affordable 'omics'-based technology has enabled faster identification of putative biomarkers, their validation is still hindered by low statistical power as well as limited reproducibility of results. Herein, through meta-analysis we have evaluated the effect size of DR regimens on adipose mass and well-recognized biomarkers of healthy aging.

Herein we included all studies evaluating the impact of DR on several healthy-associated markers in human including adipose mass. Increased visceral adiposity leads to chronic inflammation, which is often associated with a number of comorbidities (e.g. hyperinsulinemia, hypertension, insulin resistance, glucose intolerance) and reduced life expectancy. Through this meta-analysis approach, we confirmed the capacity of DR to reduce total and visceral adipose mass and, interestingly, we observed a more effective visceral adipose mass reduction after DR regimens. These findings suggest that to obtain a more effective adipose mass loss, 20% in calorie reduction could be an elective strategy. Central or visceral adiposity perturbs systemic inflammation in animal models and human and relatively to this, the healthy effects of DR could be mediated by visceral adiposity reduction. Indeed, DR significantly diminished the markers of inflammation, highlighting the central role of DR-mediated adipose tissue remodelling in improving inflammatory profile in human. Furthermore, DR also increased adiponectin/leptin ratio, which is commonly associated with ameliorated insulin sensitivity in human. In line with this effect, we demonstrated that DR was successful in reducing insulin, IGF-1 and HOMA index.

Link: http://dx.doi.org/10.18632/aging.101122


> One of the challenges for researchers in the field is to explain the reasons for this
> difference, given that the short term changes in mice and humans resulting from calorie
> restriction are in fact very similar.
One (among many) difference between human and less complex animals is that in human there are much more proteins involved in a given physiological function, for example there are ~8000 proteins in the mouse heart and ~19000 in the human heart.
Calorie restriction is linked to the cell cycle and autophagy, but the cell cycle and autophagy have little to do with the number of proteins, which itself IMO reflects more the complexity of our tissues.

Posted by: JP Le Rouzic at December 7th, 2016 10:34 AM
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