(clinical and experimental data)
Calorie restriction, SIRT1 and metabolism: understanding longevity.
Endocrine and metabolic effects of physiologic r-metHuLeptin administration during acute caloric deprivation in normal-weight women.
Food restriction, pituitary hormones and ageing.
Leptin and anti-aging action of caloric restriction.
Food restriction differentially affects pituitary hormone mRNAs throughout the adult life span of male F344 rats.
Mechanisms by which energy restriction inhibits carcinogenesis.
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.

J Clin Endocrinol Metab. 2004 Nov;89(11):5402-9.
Endocrine and metabolic effects of physiologic r-metHuLeptin administration during acute caloric deprivation in normal-weight women.
Schurgin S, Canavan B, Koutkia P, Depaoli AM, Grinspoon S.
Program in Nutritional Metabolism, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, LON 207, Boston, Massachusetts 02114, USA.

Leptin is a nutritionally regulated hormone that may modulate neuroendocrine function during caloric deficit. We hypothesized that administration of low-dose leptin would prevent changes in neuroendocrine function resulting from short-term caloric restriction. We administered physiologic doses of r-metHuLeptin [(0.05 mg/kg sc daily or identical placebo in divided doses (0800, 1400, 2000, and 0200 h)] to 17 healthy, normal-weight, reproductive-aged women during a 4-d fast. Leptin levels were lower in the placebo-treated group during fasting (3.3 +/- 0.2 vs. 9.6 +/- 1.0 ng/ml, P < 0.001, placebo vs. leptin-treated at end of study). Fat mass decreased more in the leptin than the placebo-treated group (-0.6 +/- 0.1 vs. -0.2 +/- 0.1 kg, P = 0.03). Both overnight LH area (38.9 +/- 21.5 vs. 1.2 +/- 11.1 microIU/ml.min, P = 0.05) and LH peak width increased (15.8 +/- 7.1 vs. -2.3 +/- 6.7 min, P = 0.06) and LH pulsatility decreased (-2.0 +/- 0.9 vs. 1.0 +/- 0.8 peaks/12 h, P = 0.03) more in the leptin vs. placebo group. LH pulse regularity was higher in the leptin-treated group (P = 0.02). Twenty-four-hour mean TSH decreased more in the placebo than the leptin-treated group, respectively (-1.06 +/- 0.27 vs. -0.32 +/- 0.18 microIU/ml, P = 0.03). No differences in 24-h mean GH, cortisol, IGF binding protein-1, and IGF-I were observed between the groups. Hunger was inversely related to leptin levels in the subjects randomized to leptin (r = -0.76, P = 0.03) but not placebo (r = -0.18, P = 0.70) at the end of the study. Diminished hunger was seen among subjects achieving the highest leptin levels. Our data provide new evidence of the important role of physiologic leptin regulation in the neuroendocrine response to acute caloric deprivation.

Biogerontology 2003;4(1):47-50
Food restriction, pituitary hormones and ageing.
Everitt AV.
Departments of Physiology and Anatomy & Histology F13 and Centre for Education and Research on Ageing, Concord Hospital, University of Sydney, N.S.W. 2139, Australia.

Reducing the intake of food in rodents inhibits body growth, retards most physiological ageing processes, delays the onset of pathology and prolongs life. Food restriction (FR) reduces pituitary hormone secretion and in consequence has been called 'functional hypophysectomy'. Direct life-long comparisons in the rat showed that hypophysectomy (HYP) (a complete absence of pituitary hormones) has a greater anti-ageing action than FR (a partial lack of pituitary hormones) on collagen, kidney and muscle. This suggests that pituitary hormones accelerate ageing. Recent American research on genetic variants of the mouse indicates that pituitary growth hormone (GH) may accelerate ageing and shorten life. Both the Snell and Ames dwarf mice have a deficiency of pituitary GH and live 50% longer than normal mice. The Snell dwarf mouse has retarded ageing of both collagen and immune functions. The Ames dwarf mouse has high antioxidant enzyme activities in liver and kidney. A transgenic human GH mouse is short lived, has a low activity of antioxidant enzymes in liver and kidney and an early development of disease in these organs. It is postulated that FR by reducing the secretion of pituitary hormones, such as GH, diminishes the oxidative damage of certain tissues, thereby delaying the development of age-related diseases in these tissues and by this means extends life.

J Nutr Health Aging 2001;5(1):43-8
Leptin and anti-aging action of caloric restriction.
Shimokawa I, Higami Y.
Department of Pathology, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki City 852-8523, Japan.

Evolutional theories of aging and caloric restriction (CR) in animals predict the presence of neuroendocrine signals to divert the limited energy resources from energy-costly physiologic processes such as reproduction to those essential for survival in response to food shortage. The diversion of energy and subsequent molecular mechanisms might extend the lifespan. A growing body of evidence indicates that leptin, a peptide hormone secreted from adipocytes, has a key role in neuroendocrine adaptation against life-threatening stress such as fasting. The present review discusses the potential role of leptin in the anti-aging action of CR. Although several alternative signaling pathways might also mediate the anti-aging action of CR, leptin signaling could be a substantial pathway in the CR action. Research on neuroendocrine mechanisms of CR is warranted, because such efforts might provide clues to the regulation of the aging process in humans.

J Nutr 2001 Jun;131(6):1687-93
Food restriction differentially affects pituitary hormone mRNAs throughout the adult life span of male F344 rats.
Han ES, Evans TR, Lee S, Nelson JF.
Department of Physiology, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.

Because neuroendocrine mechanisms may contribute to the antiaging effects of food restriction (FR), we measured the effect of FR on mRNAs encoding anterior pituitary (AP) tropic hormones. Slot blots or RNase protection assays were done on AP RNA from 3-, 6-, 12-, 18- and 24-mo-old male F344 rats consuming food ad libitum (AL) or food restricted (FR; to 60% of AL food intake) from 6 wk. Both AL and FR rats gained body weight during the study (P < 0.05), but FR rats weighed approximately 40% less (P < 0.0001). Messenger RNA levels were expressed in two ways, i.e., per total AP and per microgram total AP RNA. Proopiomelanocortin (POMC) mRNA/microg RNA was higher (P < 0.0005) in FR than in AL rats at all ages. Thyroid-stimulating hormone (TSH) beta mRNA declined with age (P < 0.05) in AL but not FR rats and was reduced by FR up to 12 mo (P < 0.01). Growth hormone (GH) mRNA/microg RNA declined with age (P < 0.05) in AL but not FR rats, and total GH mRNA in the AP was reduced by FR at early ages (P < 0.05). FR reduced prolactin (PRL) mRNA and its age-related increase (P < 0.0005). Levels of luteinizing hormone (LH) beta and follicle-stimulating hormone (FSH) beta mRNAs did not differ between AL and FR rats until 12 mo, but thereafter rose in FR (LH beta mRNA; P < 0.01, FSH beta mRNA; P < 0.05). Many of these changes in gene _expression corroborate previously reported hormonal changes in FR rodents and mutant mice with extended life spans, and thus provide further support for the hypothesis that an altered hormonal milieu contributes to the antiaging effects of food restriction.

Adv Exp Med Biol 1999;470:77-84
Mechanisms by which energy restriction inhibits carcinogenesis.
Thompson HJ, Jiang W, Zhu Z.
Center for Nutrition in the Prevention of Disease, AMC Cancer Research Center, Lakewood, Colorado 80214, USA.

Cancer that occurs at numerous organ sites, including the colon and breast, is inhibited by energy restriction, and the inhibition is proportional to the degree of restriction imposed. In an effort to identify the mechanism(s) by which energy restriction exerts this effect, a short term model system of experimentally induced mammary carcinogenesis was used. Given that carcinogenesis is known to involve a dysregulation to tissue size homeostasis in which cell proliferation and cell death are in dysequilibrium, we hypothesized that energy restriction exerts its effect by altering one or more aspects of cell cycle regulation. It was observed that energy restriction inhibited cell proliferation and increased cell death due to apoptosis. Thus attention was next focused on aspects of cell cycle regulation that might be affected by energy restriction. It was observed that the amount of p27 protein, one member of the Cip/Kip family of genes that are involved in cell cycle arrest, was increased dose dependently by energy restriction. Based on this and related observations, the hypothesis is advanced that energy restriction inhibits carcinogenesis, at least in part, by delaying cell cycle progression via shifting cell populations into a G(0)/G(1)state. Ongoing work indicates that corticosteroids, which are produced in increased amounts in response to energy restriction, may be involved in mediating this effect.

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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