Ketogenic Diet for Longer Life and Improved Memory

Calorie restriction, but not associated with malnutrition, has been know for many years to extend the life of lower eukaryotes and certain mammals such as mice. In mammals, the mechanism of life extension is complex but is exerted, in part, by reducing carbohydrate intake along with overall calorie restriction diets leading to a shift away from glycolysis as the primary energy producing pathway to that of fatty acid oxidation. This diet-induced metabolic shift is referred to as a ketogenic diet. I have blogged previously on the benefits of a ketogenic diet with relationship to enhanced performance during endurance workouts:

THE KETONE DIET FOR ENHANCED PHYSICAL ENDURANCE

One of the important components of life extension due to a ketogenic diet is the obvious increase in the circulating ketone, beta-hydroxybutyrate (BHB). Synthesis of BHB is primarily a response to fasting and the resultant increase in oxidation of fatty acids released from adipose tissue (fat stores). The physiological significance of BHB synthesis during fasting is that glucose intake is reduced and the ability of the liver to produce glucose (a process termed gluconeogenesis) is reduced and so the body needs to spare this limited glucose for use by red blood cells (the oxygen carrying cells of the blood) which can produce energy from no other carbon source. Under these conditions the brain, which is normally the major consumer of glucose, shifts to the use of BHB as an energy source. Recent work has demonstrated that BHB serves many critical functions that are not directly related to is function as a source of energy. BHB can inhibit inflammation, alter epigenetic regulation of gene expression, and it is also a ligand for a receptor that, when activated by BHB, modifies the metabolic activity of adipocytes (fat storing cells in adipose tissue). Details on these various non-energy producing effects of BHB can be found in my website:

https://themedicalbiochemistrypage.org/fatty-acid-oxidation.php#ketoclin

Two recent reports in the prestigious journal, Cell Metabolism, begin to dissect the molecular mechanisms that underlie the ability of a calorie restricting ketogenic diet to extend life and enhance memory functions, exerted through increased production of BHB. In these studies mice were fed diets that were nutritionally complete and consisted of low carbohydrate content with high fat content. The latter leads to induction of ketogenesis and the increased production of BHB.

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice

Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice


One of the major molecular effects of increased BHB production is the activation of the transcription factor identified as peroxisome proliferator-activated receptors alpha (PPARa). PPARa is a major regulator of the expression of genes in the liver, skeletal muscle, heart, kidney, and immune cells. Its function in the liver is to induce hepatic fatty acid oxidation during periods of fasting. Expression of PPARa is also seen macrophages (immune cells) and vascular endothelium (cells that line the inside of blood vessels). Its role in these cells is thought to be the activation of anti-inflammatory and anti-atherogenic effects. Although only very briefly outlined here, the data are complex yet highly compelling and they clearly indicate that a low carbohydrate-high fat diet induces increased production of the ketone, BHB, and that this is directly correlated to enhanced lifespan and improved memory.

It is critical to note that the typical "Western diet" is a high fat diet but it is also a high carbohydrate diet and it is no where near a calorie restricted diet. Thus, it needs to be stated that in order for humans to benefit there must be a concerted effort to lower total calories ingested and to ensure that adequate nutrition is maintained along with the low carbohydrate high fat intake. Also of significance is that the fat intake must be a balance of the beneficial and healthy fats. For more information on what constitutes healthy fats read one of my recent blog posts:

BENEFICIAL DIETARY OILS: FATS ARE NOT ALWAYS BAD FOR YOU

What is my TAKE HOME MESSAGE? Eat healthy and you may live longer and stay cogent longer!!

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