(clinical and experimental data)
Homeostatic responses to caloric restriction: Influence of background metabolic rate.
Three weeks of caloric restriction alters protein metabolism in normal weight, young men.
Calorie restriction, SIRT1 and metabolism: understanding longevity.
Regulation of uncoupling protein (UCP) 2 and 3 in adipose and muscle tissue by fasting and growth hormone treatment in obese humans.
Uncoupling protein-2 messenger ribonucleic acid _expression during very-low-calorie diet in obese premenopausal women.
J Appl Physiol. 2005 Jun 2.
Homeostatic responses to caloric restriction: Influence of background metabolic rate.
Evans SA, Parsons AD, Overton JM.
Department of Biomedical Sciences, Florida State University, Tallahassee, Florida, USA.

The biological responses to caloric restriction (CR) are generally examined in rats with elevated metabolic rates due to being housed at ambient temperatures (Ta) below the zone of thermoneutrality. We determined the physiological and behavioral responses to two weeks of 30-40% CR in male FBNF1 rats housed in cool (Ta=12 degrees C) or thermoneutral (TMN; Ta=30 degrees C) conditions. Rats were instrumented with telemetry devices and housed continuously in homecage calorimeters for the entire experiment. At baseline, rats housed in cool Ta had reduced rate of weight gain, thus a mild CR (5%) group at thermoneutrality for weight maintenance was also studied. Rats housed in cool Ta exhibited elevated caloric intake (cool= 77+/-1; TMN= 54+/-2 kcals), oxygen consumption (VO2; cool= 9.9+/-0.1; TMN=5.5+/-0.1 ml/min), mean arterial pressure (cool= 103+/-1; TMN= 80+/-2 mmHg), and heart rate (cool=374+/-3; TMN= 275+/-4 bpm). Cool-CR rats exhibited greater CR-induced weight loss (cool= -62+/-3; TMN= -42+/-3 g) and reductions in VO2 (cool= -2.6+/-0.1; TMN= -1.5+/-0.1 ml/min), but similar CR-induced reductions in heart rate (cool= -59+/-1; TMN= -51+/-7 bpm). CR had no effect on arterial blood pressure or locomotor activity in either group. Unexpectedly, weight maintenance produced significant reductions in VO2 and heart rate. At thermoneutrality , a single day of refeeding effectively abolished CRinduced reductions in VO2 and heart rate. The results reveal that rats with low or high baseline metabolic rate exhibit comparable compensatory reductions in VO2 and heart rate and suggest that Ta can be used to modulate the metabolic background upon which the more prolonged effects of CR can be studied.

Am J Physiol Endocrinol Metab. 2005 May 3.
Three weeks of caloric restriction alters protein metabolism in normal weight, young men.
Friedlander AL, Braun B, Pollack M, Macdonald JR, Fulco CS, Muza SR, Rock PB, Henderson GC, Horning MA, Brooks GA, Hoffman AR, Cymerman A.
VA Palo Alto Health Care System, Palo Alto, CA, USA; University of Massachusetts, Amherst, MA, USA.

The effects of prolonged caloric restriction on protein kinetics in lean subjects has not been previously investigated. PURPOSE: To test the hypotheses that 21 days of caloric restriction (CR) in lean subjects would a) result in significant losses of lean mass despite a suppression in leucine turnover and oxidation, and b) negatively impact exercise performance. METHODS: Nine young, normal weight men (23+/-5 y, 78.6+/-5.7 kg, VO2peak: 45.2+/-7.3 ml(.)kg(-1)(.)min(-1),mean+/-SD) were underfed by 40% of the calories required to maintain body weight (BW) for 21 days and lost 3.8+/-0.3 kg BW and 2.0+/-0.4 kg lean mass. Protein intake was kept at 1.2 g(.)kg(-1)(.)day(-1). Leucine kinetics were measured using KIC reciprocal pool model in the post-absorptive state during rest and 50 minutes of exercise (EX) at 50% of VO2peak. Body composition, basal metabolic rate (BMR) and exercise performance were measured throughout the intervention. RESULTS: At rest, leucine flux (~131 micromol(.)kg(-1)(.)hr(-1)) and oxidation (Rox; ~19 micromol(.)kg(-1)(.)hr(-1)) did not differ pre- and post- CR. During EX, leucine flux (129+/-6 vs. 121+/-6) and Rox (54+/-6 vs. 46+/-8)were lower following CR than pre-CR. Nitrogen balance was negative throughout the intervention (~3.0gN(.)d(-1)) and BMR declined from 1898+/-262 kcal(.)d(-1) to 1670+/-203. Aerobic performance (VO2peak, endurance cycling) was not impacted by CR, but arm flexion endurance decreased by 20%. CONCLUSIONS: Three weeks of caloric restriction reduced leucine flux and oxidation during exercise in normal weight young men. However, despite negative nitrogen balance and loss of lean mass, whole body exercise performance was well maintained in response to CR.

Nat Rev Mol Cell Biol. 2005 Apr;6(4):298-305.
Calorie restriction, SIRT1 and metabolism: understanding longevity.
Bordone L, Guarente L.
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Calorie restriction (CR) is the only experimental manipulation that is known to extend the lifespan of a number of organisms including yeast, worms, flies, rodents and perhaps non-human primates. In addition, CR has been shown to reduce the incidence of age-related disorders (for example, diabetes, cancer and cardiovascular disorders) in mammals. The mechanisms through which this occurs have been unclear. CR induces metabolic changes, improves insulin sensitivity and alters neuroendocrine function in animals. In this review, we summarize recent findings that are beginning to clarify the mechanisms by which CR results in longevity and robust health, which might open new avenues of therapy for diseases of ageing.

Int J Obes Relat Metab Disord 2000 Aug;24(8):968-75
Regulation of uncoupling protein (UCP) 2 and 3 in adipose and muscle tissue by fasting and growth hormone treatment in obese humans.
Pedersen SB, Borglum JD, Kristensen K, Norrelund H, Otto J, Jorgensen L, Richelsen B.
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus Amtssygehus, DK-8000 Aarhus C, Denmark.

To investigate whether the _expression of uncoupling proteins (UCP2 and UCP3) was affected by a very low calorie diet (VLCD) and growth hormone (GH) treatment for 4 weeks. DESIGN: A randomized, placebo-controlled intervention study of VLCD with or without concomitant GH-treatment. SUBJECTS: Seventeen obese women (body mass index, BMI=42.1+/-1.4 kg/m2 (range 31.8-54.5 kg/m2)) treated with VLCD for 4 weeks and randomized to concomitant placebo treatment (n=9) or GH treatment (n=8). MEASUREMENTS: Fat mass and lean body mass were measured by dual-energy X-ray absorptiometry. Energy expenditure (EE) was measured by indirect calorimetry. UCP2 and UCP3 mRNA were measured in adipose tissue and skeletal muscle biopsies before VLCD and after VLCD+/-GH-treatment by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: VLCD treatment resulted in a mean weight loss of 5.23 kg+/-0.8 (P<0.01), a 4.1% decrease in EE (P<0.05) and a 24% decrease in UCP3 mRNA in adipose tissue (P<0.03), whereas adipose tissue UCP2 mRNA and skeletal muscle UCP2 and UCP3 mRNA levels were unchanged. GH-treatment had no effects on EE, changes in body weight or UCP mRNA level. In multiple regression analysis the change in EE caused by VLCD was significantly correlated with changes in adipose tissue UCP2 mRNA (r=0.66, P<0.02) and a tendency towards a significant association with the change in adipose tissue UCP3 mRNA (r=0.45, P=0.09), but not with change in body weight, skeletal muscle UCP2 or UCP3 mRNA levels. CONCLUSION: VLCD for 4 weeks decreased UCP3 mRNA _expression in human adipose tissue, whereas GH-treatment had no effect on UCP _expression. Multiple regression analysis demonstrated that changes in adipose tissue UCP2 and probably UCP3 mRNA were correlated with the change in EE. These findings indicate that UCPs in adipose tissue in very obese individuals might play a role for the reduction in EE observed during energy restriction.

J Clin Endocrinol Metab 1998 Jul;83(7):2450-3
Uncoupling protein-2 messenger ribonucleic acid _expression during very-low-calorie diet in obese premenopausal women.
Barbe P; Millet L; Larrouy D; Galitzky J; Berlan M; Louvet JP; Langin D.
INSERM Unit 317, Louis Bugnard Institute, Rangueil Hospital, Paul Sabatier University, Toulouse, France.

Uncoupling protein-2 (UCP2) is a mitochondrial protein expressed in a wide range of human tissues. By uncoupling respiration from ATP synthesis, UCP2 might be involved in the control of energy expenditure. We have investigated UCP2 gene _expression in human adipose tissue. In eight subjects, we found a positive correlation (r = 0.91, P < 0.002) between subcutaneous and visceral fat depots UCP2 messenger RNA (mRNA) levels, suggesting that UCP2 mRNA level in subcutaneous adipose tissue is a good index of UCP2 gene _expression in whole body adipose tissues. The effect of a 25-day very-low-calorie diet un UCP2 mRNA level and resting metabolic rate was investigated in eight obese premenopausal women. There was no difference in UCP2 mRNA levels before and during the diet. After 25 days of hypocaloric diet, a positive correlation was found between adipose tissue UCP2 mRNA level and resting metabolic rate adjusted for lean body mass (r = 0.82, P < 0.01). These results show that very-low-calorie diet, unlike short-term fasting, is not associated with an induction in UCP2 mRNA _expression, and that adipose tissue UCP2 mRNA levels may be related to variations in resting energy expenditure in humans.

on the Adriatic Coast
The Anti-Aging Fasting Program consists of a 7-28 days program (including 3 - 14 fasting days). 7-28-day low-calorie diet program is also available .
More information
    The anti-aging story (summary)
Introduction. Statistical review. Your personal aging curve
  Aging and Anti-aging. Why do we age?
    2.1  Aging forces (forces that cause aging
Internal (free radicals, glycosylation, chelation etc.) 
External (Unhealthy diet, lifestyle, wrong habits, environmental pollution, stress, poverty-change "poverty zones", or take it easy. etc.) 
    2.2 Anti-aging forces
Internal (apoptosis, boosting your immune system, DNA repair, longevity genes) 
External (wellness, changing your environment; achieving comfortable social atmosphere in your life, regular intake of anti-aging drugs, use of replacement organs, high-tech medicine, exercise)
    2.3 Aging versus anti-aging: how to tip the balance in your favour!
    3.1 Caloric restriction and fasting extend lifespan and decrease all-cause mortality (Evidence)
      Human studies
Monkey studies
Mouse and rat studies
Other animal studies
    3.2 Fasting and caloric restriction prevent and cure diseases (Evidence)
Hypertension and Stroke
Skin disorders
Mental disorders
Neurogical disorders
Asthmatic bronchitis, Bronchial asthma
Bones (osteoporosis) and fasting
Arteriosclerosis and Heart Disease
Cancer and caloric restriction
Cancer and fasting - a matter of controversy
Eye diseases
Chronic fatigue syndrome
Sleeping disorders
Rheumatoid arthritis
Gastrointestinal diseases
    3.3 Fasting and caloric restriction produce various
      biological effects. Effects on:
        Energy metabolism
Lipids metabolism
Protein metabolism and protein quality
Neuroendocrine and hormonal system
Immune system
Physiological functions
Reproductive function
Cognitive and behavioral functions
Biomarkers of aging
    3.4 Mechanisms: how does calorie restriction retard aging and boost health?
        Diminishing of aging forces
  Lowering of the rate of gene damage
  Reduction of free-radical production
  Reduction of metabolic rate (i.e. rate of aging)
  Lowering of body temperature
  Lowering of protein glycation
Increase of anti-aging forces
  Enhancement of gene reparation
  Enhancement of free radical neutralisation
  Enhancement of protein turnover (protein regeneration)
  Enhancement of immune response
  Activation of mono-oxygenase systems
  Enhance elimination of damaged cells
  Optimisation of neuroendocrine functions
    3.5 Practical implementation: your anti-aging dieting
        Fasting period.
Re-feeding period.
Safety of fasting and low-calorie dieting. Precautions.
      3.6 What can help you make the transition to the low-calorie life style?
        Social, psychological and religious support - crucial factors for a successful transition.
Drugs to ease the transition to caloric restriction and to overcome food cravings (use of adaptogenic herbs)
Food composition
Finding the right physician
    3.7Fasting centers and fasting programs.
  Food to eat. Dishes and menus.
    What to eat on non-fasting days. Dishes and menus. Healthy nutrition. Relation between foodstuffs and diseases. Functional foods. Glycemic index. Diet plan: practical summary. "Dr. Atkins", "Hollywood" and other fad diets versus medical science

Bread, cereals, pasta, fiber
Glycemic index
Meat and poultry
Sugar and sweet
Fats and oils
Dairy and eggs
Nuts and seeds
Food composition

  Anti-aging drugs and supplements
    5.1 Drugs that are highly recommended
      (for inclusion in your supplementation anti-aging program)
        Vitamin E
Vitamin C
Co-enzyme Q10
Lipoic acid
Folic acid
Flavonoids, carotenes
Vitamin B
Vinpocetine (Cavinton)
Deprenyl (Eldepryl)
    5.2 Drugs with controversial or unproven anti-aging effect, or awaiting other evaluation (side-effects)
        Phyto-medicines, Herbs
      5.3 Drugs for treatment and prevention of specific diseases of aging. High-tech modern pharmacology.
        Alzheimer's disease and Dementia
Immune decline
Infections, bacterial
Infections, fungal
Memory loss
Muscle weakness
Parkinson's disease
Prostate hyperplasia
Sexual disorders
Stroke risk
Weight gaining
    5.4 The place of anti-aging drugs in the whole
      program - a realistic evaluation
    6.1 Early diagnosis of disease - key factor to successful treatment.
      Alzheimer's disease and Dementia
Cataracts and Glaucoma
Genetic disorders
Heart attacks
Immune decline
Infectious diseases
Memory loss
Muscle weakness
Parkinson's disease
Prostate hyperplasia
Stroke risk
Weight gaining
    6.2 Biomarkers of aging and specific diseases
    6.3 Stem cell therapy and therapeutic cloning
    6.4 Gene manipulation
    6.5 Prosthetic body-parts, artificial organs
Bones, limbs, joints etc.
Heart & heart devices
    6.6 Obesity reduction by ultrasonic treatment
  Physical activity and aging. Experimental and clinical data.
        Aerobic exercises
Weight-lifting - body-building
Professional sport: negative aspects
  Conclusion: the whole anti-aging program
    9.1 Modifying your personal aging curve
      Average life span increment. Expert evaluation.
Periodic fasting and caloric restriction can add 40 - 50 years to your lifespan
Regular intake of anti-aging drugs can add 20-30 years to your lifespan
Good nutrition (well balanced, healthy food, individually tailord diet) can add 15-25 years to your lifespan
High-tech bio-medicine service can add 15-25 years to your lifespan
Quality of life (prosperity, relaxation, regular vocations) can add 15-25 years to your lifespan
Regular exercise and moderate physical activity can add 10-20 years to your lifespan
These approaches taken together can add 60-80 years to your lifespan, if you start young (say at age 20). But even if you only start later (say at 45-50), you can still gain 30-40 years

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    9.2 The whole anti-aging life style - brief summary 
    References eXTReMe Tracker
        The whole anti-aging program: overview

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