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PERIODIC FASTING AND CALORIC RESTRICTION FOR LIFE EXTENSION, TREATMENT OF DISEASE,
AND ENHANCED CREATIVITY.
(clinical and experimental data)
 
  PHYSIOLOGICAL  
   
 
Metabolism and thermoregulation during fasting in king penguins, Aptenodytes patagonicus, in air and water.
Regional-dependent Increase of Sympathetic Innervation in Rat White Adipose Tissue during Prolonged Fasting.
Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction.
Morphometry of fine structural alterations of hepatocytes of Japanese monkeys under fasting stress.
 
   
   

2005

Am J Physiol Regul Integr Comp Physiol. 2005 May 12.
Metabolism and thermoregulation during fasting in king penguins, Aptenodytes patagonicus, in air and water.
Fahlman A, Schmidt A, Handrich Y, Woakes AJ, Butler PJ.
School of Biosciences, The University of Birmingham, Birmingham, United Kingdom.

We measured rate of oxygen consumption (VO2) and body temperatures in 10 king penguins in air and water. VO2 was measured during rest and at submaximal and maximal exercise before (fed) and after (fasted) an average fasting duration of 14.4 +/- 2.3 days (mean +/- 1 SD, range 10-19 days) in air and water. Concurrently, we measured subcutaneous temperature and temperature of the upper (heart and liver), middle (stomach) and lower (intestine) abdomen. The mean body mass was 13.8 +/- 1.2 kg in fed and 11.0 +/- 0.6 kg in fasted birds. After fasting, resting VO2 was 93% higher in water than in air (air: 86.9 +/- 8.8 ml (.) min(-1); water: 167.3 +/- 36.7 ml (.) min(-1), P < 0.01), while there was no difference in resting VO2 between air and water in fed animals (air: 117.1 +/- 20.0 ml 02 (.) min(-1) water: 114.8 +/- 32.7 ml 02 (.) min(-1), P > 0.6). In air, VO2 decreased with body mass while it increased with body mass in water. Body temperature did not change with fasting in air whereas in water, there were complex changes in the peripheral body temperatures. These latter changes may, therefore, be indicative of a loss in body insulation and of variations in peripheral perfusion. Four animals were given a single meal after fasting and the temperature changes were partly reversed 24 h after re-feeding in all body regions except the subcutaneous, indicating a rapid reversal to a pre-fasting state where body heat loss is minimal. The data emphasize the importance in considering nutritional status when studying king penguins and that the fasting-related physiological changes diverge in air and water.

   
   
J Histochem Cytochem. 2005 Jun;53(6):679-87.
Regional-dependent Increase of Sympathetic Innervation in Rat White Adipose Tissue during Prolonged Fasting.
Giordano A, Frontini A, Murano I, Tonello C, Marino MA, Carruba MO, Nisoli E, Cinti S.
Institute of Normal Human Morphology, Marche Polytechnic University, Via Tronto, 10/A, 60020 Ancona, Italy.

White adipose tissue (WAT) is innervated by the sympathetic nervous system. A role for WAT sympathetic noradrenergic nerves in lipid mobilization has been suggested. To gain insight into the involvement of nerve activity in the delipidation process, WAT nerves were investigated in rat retroperitoneal and epididymal depots after prolonged fasting. A significant increase in tyrosine hydroxylase (TH) content was found in epididymal and, especially, retroperitoneal WAT by Western blotting. Accordingly, an increased immunoreactivity for TH was detected by immunohistochemistry in epididymal and, especially, retroperitoneal vascular and parenchymal noradrenergic nerves. Neuropeptide Y (NPY)-containing nerves were found around arteries and in the parenchyma. Double-staining experiments and confocal microscopy showed that most perivascular and some parenchymal noradrenergic nerves also contained NPY. Detection of protein gene product (PGP) 9.5, a general marker of peripheral nerves, by Western blotting and PGP 9.5-TH by double-staining experiments showed significantly increased noradrenergic nerve density in fasted retroperitoneal, but not epididymal depots, suggesting that formation of new nerves takes place in retroperitoneal WAT in fasting conditions. On the whole, these data confirm the important role of sympathetic noradrenergic nerves in WAT lipid mobilization during fasting but also raise questions about the physiological role of regional-dependent nerve adjustments and their functional significance in relation to white adipocyte secretory products.

   
   
Mech Ageing Dev. 2005 May 28.
Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction.
Spindler SR.
Department of Biochemistry, University of California, Riverside, CA 92521, USA.

It is widely held that caloric restriction (CR) extends lifespan by preventing or reducing the age-related accumulation of irreversible molecular damage. In contrast, our results suggest that CR can act rapidly to begin life and health span extension, and that its rapid genomic effects are closely linked to its health effects. We found that CR begins to extend lifespan and reduce cancer as a cause of death within 8 weeks in older mice, apparently by reducing the rate of tumor growth. Further, 8 weeks of CR progressively reproduces nearly three quarters of the genomic effects of long-term CR (LTCR) in liver. Fewer of the genomic effects of LTCR are rapidly reproduced by the initiation of CR in the heart, but the changes produced are keys to cardiovascular health. Thus, the genomic effects of CR may be established more rapidly in mitotic than in postmitotic tissues. Most of the genomic effects of LTCR dissipate 8 weeks after switching to a control diet. Consistent with these results, others have shown that acute CR rapidly and reversibly reduces the short-term risk of death in Drosophila to that of LTCR treated flies. Further, in late adulthood, acute CR partially or completely reverses age-related alterations of liver, brain and heart proteins. CR also rapidly and reversibly mitigates biomarkers of aging in adult rhesus macaques and humans. These data argue that highly conserved mechanisms for the rapid and reversible enhancement of life- and health-span exist for mitotic and postmitotic tissues.

   
   

1998

J Vet Med Sci 1998 Jul;60(7):849-52.
Morphometry of fine structural alterations of hepatocytes of Japanese monkeys under fasting stress.
Yang YG; Makita T.
Department of Veterinary Anatomy, Faculty of Agriculture, Yamaguchi University, Japan.

The fine structural alterations of hepatocytes of Japanese monkeys under 4 days of fasting stress were analyzed morphometrically. One of the conspicuous alterations was the enlargement of mitochondria. The average diameter of mitochondria in fasting group increased to approximately 1.89-fold of that in control group, though their number did not change. The number of peroxisomes was 1.36-fold of that in control, though their area did not change. In addition, many of r-ER were swollen and were vesiculated. The appearance of bundle of actin-like stress fiber also increased in the fasting animals. The glycogen area as well as liver weight decreased in fasting group.