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Stephen Ginsberg and the Low-cal Diet that Slows Aging

Robert Cavanaugh

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The data keeps mounting for the benefits of CR. Interestingly, many of the genes that are altered by CR overlap with those related to circadian rhythms in metabolically active tissues. CR very potently entrains peripheral circadian rhythms, as well as influencing central circadian control. Meal timing has a secondary effect and version of intermittent fasting that appear to mimic some of the benefits of CR probably derive partly from this.


Not free full-text, but the abstract gives some info on this.




The relationship between nutrition and circadian rhythms in mammals.
Froy O.
Front Neuroendocrinol. 2007 Aug-Sep;28(2-3):61-71. Epub 2007 Mar 24.
The master clock located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus regulates circadian rhythms in mammals. The clock is an intracellular, transcriptional mechanism sharing the same molecular components in SCN neurons and in peripheral cells, such as the liver, intestine, and retina. The circadian clock controls food processing and energy homeostasis by regulating the expression and/or activity of enzymes involved in cholesterol, amino acid, lipid, glycogen, and glucose metabolism. In addition, many hormones involved in metabolism, such as insulin, glucagon, adiponectin, corticosterone, leptin, and ghrelin, exhibit circadian oscillation. Furthermore, disruption of circadian rhythms is involved in the development of cancer, metabolic syndrome, and obesity. Metabolism and food intake also feed back to influence the biological clock. Calorie restriction (CR) entrains the SCN clock, whereas timed meals entrain peripheral oscillators. Furthermore, the cellular redox state, dictated by food metabolism, and several nutrients, such as glucose, ethanol, adenosine, caffeine, thiamine, and retinoic acid, can phase-shift circadian rhythms. In conclusion, there is a large body of evidence that links feeding regimens, food components, and the biological clock.


This is a great paper that explains how disrupted circadian clocks, as well as the general loss of circadian control with age, leads to metabolic and genomic abnormalities and physiological degeneration.





The aging clock and circadian control of metabolism and genome stability.
Belancio VP, Blask DE, Deininger P, Hill SM, Jazwinski SM.
Front Genet. 2015 Jan 14;5:455. doi: 10.3389/fgene.2014.00455. eCollection 2014.
It is widely accepted that aging is characterized by a gradual decline in the efficiency and accuracy of biological processes, leading to deterioration of physiological functions and development of age-associated diseases. Age-dependent accumulation of genomic instability and development of metabolic syndrome are well-recognized components of the aging phenotype, both of which have been extensively studied. Existing findings strongly support the view that the integrity of the cellular genome and metabolic function can be influenced by light at night (LAN) and associated suppression of circadian melatonin production. While LAN is reported to accelerate aging by promoting age-associated carcinogenesis in several animal models, the specific molecular mechanism(s) of its action are not fully understood. Here, we review literature supporting a connection between LAN-induced central circadian disruption of peripheral circadian rhythms and clock function, LINE-1 retrotransposon-associated genomic instability, metabolic deregulation, and aging. We propose that aging is a progressive decline in the stability, continuity, and synchronization of multi-frequency oscillations in biological processes to a temporally disorganized state. By extension, healthy aging is the ability to maintain the most consistent, stable, and entrainable rhythmicity and coordination of these oscillations, at the molecular, cellular, and systemic levels.
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  • 3 weeks later...

Hi James and Bob!


The link that Bob sent us, about Prof. Ginsberg, indicates that over 900 brain-related genes showed improvement in his CR mouse studies -- that almost probably includes many in addition to those related to the circadian rythms (which of course are important, too).


  -- Saul

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