Josh Mitteldorf

Caloric restriction

“If there is very little food … the last thing you need is to add to the death rate with aging and the weakening that comes with age. The best thing you can do is to live a long time, don’t have your children yet, but you wait for the famine to be over. When the famine is over, then you have your children and you can ensure the continuation of the population. I see the caloric restriction effect as a population stabilization adaptation. And then the whole thing makes sense.”

Intermittent fasting

The Sheekey Science Show

Did you know that when you eat is just as important as what you eat? Why? When is best to eat? Why does it matter? In this video i discuss intermittent fasting (IF), the different types of IF compare it to calorie restriction, look at the health benefits and human clinical trial studies, discuss some problems and practical considerations and discuss a future outlook.

Long-term caloric restriction


Objectives: We determined whether caloric restriction (CR) has cardiac-specific effects that attenuate the established aging-associated impairments in diastolic function.

Background: Caloric restriction retards the aging process in small mammals; however, no information is available on the effects of long-term CR on human aging. In healthy individuals, Doppler echocardiography has established the pattern of aging-associated diastolic impairment, whereas little change is observed in systolic function.

Methods: Diastolic function was assessed in 25 subjects (age 53 +/- 12 years) practicing CR for 6.5 +/- 4.6 years and 25 age- and gender-matched control subjects consuming Western diets. Diastolic function was quantified by transmitral flow, Doppler tissue imaging, and model-based image processing (MBIP) of E waves. C-reactive protein (CRP), TNF-alpha and TGF-beta1 were also measured.

Results: No difference in systolic function was observed between groups; however, standard transmitral Doppler flow diastolic function indexes of the CR group were similar to those of younger individuals, and MBIP-based, flow-derived diastolic function indexes, reflecting chamber viscoelasticity and stiffness, were significantly lower than in control subjects.

Blood pressure, serum CRP, TNF-alpha, and TGF-beta1 levels were significantly lower in the CR group (102 +/- 10/61 +/- 7 mm Hg, 0.3 +/- 0.3 mg/l, 0.8 +/- 0.5 pg/ml, 29.4 +/- 6.9 ng/ml, respectively) compared with the Western diet group (131 +/- 11/83 +/- 6 mm Hg, 1.9 +/- 2.8 mg/l, 1.5 +/- 1.0 pg/ml, 35.4 +/- 7.1 ng/ml, respectively).

Conclusions: Caloric restriction has cardiac-specific effects that ameliorate aging-associated changes in diastolic function. These beneficial effects on cardiac function might be mediated by the effect of caloric restriction on blood pressure, systemic inflammation, and myocardial fibrosis.

SOURCE: J Am Coll Cardiol

EDITOR’S NOTE: The middle-aged adults in the calorie restriction group maintained an average blood pressure (102/61) that in Western society is normally characteristic of a pre-teen.

Does eating less make you live longer?


The complexity of aging is hard to be captured. However, apart from its tissue-specific features, a structural and functional progressive decline of the whole organism that leads to death, often preceded by a phase of chronic morbidity, characterizes the common process of aging. Therefore, the research goal of scientists in the field moved from the search for strategies able to extend longevity to those ensuring healthy aging associated with a longer lifespan referred to as “healthspan”.

The aging process is plastic and can be tuned by multiple mechanisms including dietary and genetic interventions. To date, the most robust approach, efficient in warding off the cellular markers of aging, is calorie restriction (CR).

Here, after a preliminary presentation of the major debate originated by CR, we concisely overviewed the recent results of CR treatment on humans. We also provided an update on the molecular mechanisms involved by CR and the effects on some of the age-associated cellular markers. Finally, we reviewed a number of tested CR mimetics and concluded with an evaluation of future applications of such dietary approach.

Calorie restriction


Nutrient and stress sensors mediate lifespan extensions that occur in response to many different environmental and physiological signals. The best known of these signals is dietary restriction, which extends lifespan in many species, from yeast to primates.

Dietary restriction was initially assumed to extend lifespan simply by reducing the rate at which cellular damage accumulates over time as a result of nutrient metabolism. Recently, however, an elegant experiment with Drosophila showed that dietary restriction produces a rapid decrease in the mortality rate (the daily chance of death), suggesting that dietary restriction counteracts the causes of ageing in an acute manner.

We now know that the longevity response to dietary restriction is actively regulated by nutrient-sensing pathways involving the kinase target of rapamycin (TOR), AMP kinase, sirtuins and insulin/insulin-like growth factor (IGF-1) signalling.

Unexpectedly, which nutrient sensor is most important in extending lifespan in response to dietary restriction depends on the way that dietary restriction is imposed. In C. elegans, for example, one nutrient sensor extends lifespan in response to life-long food limitation, another in response to every-other-day feeding and a third if dietary restriction begins in middle age.

SOURCE: Nature (2010)

Caloric restriction ± exercise


Calorie restriction (CR) delays the development of age-associated disease and increases lifespan in rodents, but the effects in humans remain uncertain.

Purpose. Determine the effect of 6 months of CR with or without exercise on cardiovascular disease (CVD) risk factors and estimated 10-year CVD risk in healthy non-obese men and women.

Methods. Thirty-six individuals were randomized to one of three groups for 6 months: Control, 100% of energy requirements; CR, 25% calorie restriction; CR+EX, 12.5% CR + 12.5% increase in energy expenditure via aerobic exercise. CVD risk factors were assessed at baseline, 3 and 6 months.

Results. After 6 months, CR and CR+EX lost approximately 10% of body weight. CR significantly reduced triacylglycerol (-31 ± 15 mg/dL) and factor VIIc (-10.7 ± 2.3%). Similarly CR+EX reduced triacylglycerol (-22 ± 8 mg/dL) and additionally reduced LDL-C (-16.0 ± 5.1 mg/dL) and DBP (-4.0 ± 2.1 mmHg). In contrast, both triacylglycerol (24 ± 14 mg/dL) and factor VIIc (7.9 ± 2.3%) were increased in the control group. HDL-cholesterol was increased in all groups while hsCRP was lower in the Controls vs. CR+EX. Estimated 10-year CVD risk significantly declined from baseline by 29% in CR (P< 0.001) and 38% in the CR+EX (P<0.001) while remaining unchanged in the Control group.

Conclusions. Based on combined favorable changes in lipid and blood pressure, caloric restriction with or without exercise that induces weight loss favorably reduces risk for CVD even in already healthy non-obese individuals.

SOURCE: Atherosclerosis