mitohormesis

A few weeks ago I posted a link to this article – Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health – from none other than Jeff Volek (yep, one of the scientific heavy-weights in the ketosis world), VJ Miller, and FA Villamena.

[Citation: Journal of Nutrition and Metabolism. 2018; 2018: 5157645]

IMHO, for those interested in digging a bit deeper into a science behind why nutritional ketosis (NK) provides the hosts of benefits it does, this will go down as one of the landmark articles detailing in particular NK’s impact at the mitochondrial level.

Why does that matter? From the abstract (cited above) –

The free radical theory of aging proposes that reactive oxygen species (ROS)-induced accumulation of damage to cellular macromolecules is a primary driving force of aging and a major determinant of lifespan. Although this theory is one of the most popular explanations for the cause of aging, several experimental rodent models of antioxidant manipulation have failed to affect lifespan. Moreover, antioxidant supplementation clinical trials have been largely disappointing. The mitochondrial theory of aging specifies more particularly that mitochondria are both the primary sources of ROS and the primary targets of ROS damage. In addition to effects on lifespan and aging, mitochondrial ROS have been shown to play a central role in healthspan of many vital organ systems. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and dysfunction in aging and healthspan, including cardiac aging, age-dependent cardiovascular diseases, skeletal muscle aging, neurodegenerative diseases, insulin resistance and diabetes as well as age-related cancers…

They go on to discuss the roll that reactive oxygen species (ROS) play in tissue/cellular damage (one of the principal driving forces of aging), the ‘built-in’ systems designed to mitigate ROS damage, and the lackluster results in large scale trials of antioxidants with regards to mortality and morbidity, with a possible exception being Alzheimer’s disease.

They focus a large part of discussion on the mitochondrial free radical theory of aging, which (as complex as it is) is discussed in detail, leading to presentation of the key concept of mitochondrial signaling and mitohormesis –

Apart from generating detrimental oxidative damage, ROS have numerous crucial biological roles in signaling and stress response (reviewed in [33-35]). Emerging evidence suggests that oxidative stress might promote longevity and metabolic health through the concept of mitochondrial hormesis (mitohormesis). The mitohormesis theory hypothesizes that low levels of oxidative stress induced by either caloric restriction, exercise [36], or other stimuli may trigger adaptive responses that improve overall stress resistance, probably through increased endogenous antioxidant defense, which may eventually reduce chronic oxidative damage [37] and subsequently achieve lifespan extension…

The Take Away

While part of the paper details the ongoing search for and testing of pharmacologic agents which induce mitohormesis, the authors clearly reference studies and the science supporting nutritional ketosis, calorie restriction, and exercise (among others) as potential drivers of mitohormesis.

NK’s ability, when properly executed, to induce / encourage these types of adaptive changes at the cellular level is quite impressive, and should lead most to take a more serious look at using NK as an intermittent tool to improve their health.

The paper happens to be extensively referenced, and for those who want to dig deeper into NK, there are several weeks of additional reading and pondering to do…