The study below is one of the few to directly challenge the so-called Rate of Living Theory (ROL) that has dominated (and continues to dominate) medical research in aging/longevity. The study demonstrates that administering an OXPHOS uncoupler (which compensatorily increases the metabolic rate and heat production) extended maximum lifespan of the studied organism by up to 25%, while simultaneously also increasing healthspan (the period of time in an organism’s lifespan that is free of major disease). The study used the uncoupler BAM15 to achieve those effects, however this is a very suboptimal choice due to the known toxicity of the chemical resulting mostly likely from the presence of fluorine in the molecule. Had the study used a more benign uncoupler such as 2,4-dinitropheol (DNP), aspirin/salicylates, the active thyroid hormone T3, progesterone, DHEA, salt, etc it is likely that the results would have been much more impressive. Be that as it may, we now have evidence that the ROL is wrong and the truth about longevity and aging is exactly backwards. Namely, the higher the basal metabolic rate the longer one lives and the healthier one is. Just as importantly, the findings of the study directly question the current established recommendations to exercise rigorously as exhaustive exercise (especially the “endurane” type) is one of the most well-known metabolic suppressors. If an exercise regimen is desired it should consist of mostly concentric exercise, and done only for periods that are so-called glycogen-bound – i.e. exercise should be performed only until the fuel used is primarily glucose, from food of from internal glycogen storage. As soon as glucose is depleted and fat burning (precedes by elevated lipolysis) starts the exercise quickly starts to become detrimental. Not just to the metabolic rate but to the entire organism due to switching over to fat-burning, with the added “bonus” that for most people the fat being released from stores and oxidized will be PUFA as that type of fat is preferentially stored into adipose tissue. And last but not least, the popular press article is one again exposing the cunning nature of scientific “journalism”. Instead of reporting the actual findings of the study, which directly state that metabolic uncoupling and increased metabolic rate/thermogenesis extends lifespan, the article states that “making the cells less efficient at producing energy” is what extends lifespan. While technically correct, the message most people would internalize from the article is that the ROL is correct since for most people reduced energy production implies reduced metabolism.
https://doi.org/10.1111/acel.14107
“…A new study has shown that BAM15, a compound that makes mitochondria less efficient at producing energy, extended life span in fruit flies and was associated with less body fat and increased muscle function. The paper is titled “Restricting bioenergetic efficiency enhances longevity and mitochondrial redox capacity in Drosophila melanogaster” and is published in the journal Aging Cell.”
“…This current study is the first to show that adding BAM15 to the diet can uncouple mitochondria, extend life span, improve body composition, and protect against age-related decline in motor activity in a fruit fly model of aging. The authors state, “In summary, our findings indicate that mitochondrial uncoupling by BAM15 confers life span extension, improves body composition, and protects against age-related decline in locomotor activity in Drosophila (fruit flies). Collectively, these data support an emerging role for restricting bioenergetic efficiency to maintain mitochondrial redox fitness across the life span.”
