Calorie Restriction Produces Benefits via Increased Autophagy

It is fairly well established by this point that calorie restriction boosts the cellular housekeeping processes known as autophagy. Damaged components, broken proteins, and other issues are more readily dealt with, destroyed, and recycled when an individual is on a low calorie rather than high calorie diet. Increased levels of autophagy are known to be associated with many of the methods of slowing aging demonstrated in laboratory animals, which leads some researchers to think that it is one of the more important aspects of the way in which metabolism determines variations in longevity. With that in mind, here is one of a range of studies that confirm the association between calorie restriction and increased autophagy:

Diet has been long recognized as a modulator of kidney health in both humans and experimental models. Calorie restriction (CR) can retard the progression of many age-associated molecular, physiological, and pathological processes which occur in tissues with high oxidative demand, such as kidney, skeletal muscle, heart, and brain. In contrast, feeding mice with a high-calorie diet results in age-related obesity, cardiovascular diseases, and other metabolic disorders, and it shortens lifespan. A high-calorie (HC) diet induces renal injury and promotes aging, and calorie restriction (CR) may ameliorate these responses. However, the effects of long-term HC and CR on renal damage and aging have been not fully determined.

Autophagy is an evolutionarily conserved process in eukaryotic organisms. Cytoplasmic constituents are sequestered in double-membrane structures to form autophagosomes, which fuse with lysosomes to form autolysosomes. The cytoplasmic components are degraded by acid hydrolases, and the degradation products are released into the cytosol and recycled into biological structures or to supply energy during periods of starvation. Autophagy is critical for survival during nutrient deprivation, as it enables recycling of macromolecules to provide new nutrients and energy in yeast and mammals. Another key function of autophagy is to remove damaged organelles such as mitochondria and aberrant macromolecules, to prevent further injury to cells. Therefore, impairment of autophagy will lead to a progressive accumulation of damaged macromolecules and organelles in somatic cells, increased oxidative damage and accelerated aging.

We evaluated the expression of [markers of autophagy] in the kidneys of 24-month-old Fischer 344 rats. We also observed mitochondrial structure and autolysosomes by transmission electron microscopy. Expression of the autophagosome formation marker LC3/Atg8 and markers of mitochondrial autophagy (mitophagy) were markedly decreased in the kidneys of the HC group, and markedly increased in CR kidneys. Transmission electron microscopy demonstrated that HC kidneys showed severe abnormal mitochondrial morphology with fewer autolysosomes, while CR kidneys exhibited normal mitochondrial morphology with numerous autolysosomes. Markers of aging, such as p16 and senescence-associated-galactosidase, were increased significantly in the HC group and decreased significantly in the CR group. The study [suggests] that HC diet inhibits renal autophagy and aggravates renal oxidative damage and aging, while CR enhances renal autophagy and ameliorates oxidative damage and aging in the kidneys.



As we know, periodic or intermittent fasting is an easier lifestyle than CR. It's also probably a more efficient way to create autophogy. I just wish there was better consensus on how long it takes to achieve this coveted elixir state of being. Everything I read pegs it anywhere from 16 hours to 3 days before autophogy can happen. One book even says you can achieve it simply by restricting protein for 24 hours, bypassing the need for total fasting. If anyone has a better educated handle on this timeframe than me, please let me know.

Posted by: August33 at December 19th, 2019 8:45 AM
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