In studying ways to extend the life span and improving the health at late age of lab animals, my colleagues and I saw a consistent pattern: All the anti-aging interventions we tested led to reduced glycerol levels.
We hypothesized that elevated ADH-1 activity promotes health in old age by decreasing harmful levels of glycerol.
Supporting this hypothesis were two critical observations. First, we found that adding glycerol to the diet of worms shortened their life span by 30 percent. By contrast, animals genetically modified to boost levels of the glycerol-busting enzyme ADH-1 had low glycerol levels and remained lean and healthy with longer lives, even on unrestricted diets.
The simple molecular structure and wealth of research on ADH-1 make it an attractive target for developing drugs that boost its activity. My lab’s long-term goal is to explore how compounds that activate ADH-1 affect the health and longevity of both mice and people.
Rapamycin is everywhere (in longevity research) these days, it seems…
We saw similar high ADH-1 activity levels in people undergoing dietary restriction or treated with an anti-aging drug called rapamycin. This finding suggests there may be a common mechanism underlying healthy aging across species, with ADH-1 at its core.
See this paper (referenced in link in the quote above):
Increased alcohol dehydrogenase 1 activity promotes longevity
https://www.cell.com/current-biology/fulltext/S0960-9822(23)00128-8
The sole overexpression of ADH-1 is sufficient to activate AMAR, which extends healthspan and lifespan by reducing the levels of glycerol—an age-associated and aging-promoting alcohol. Adh1 overexpression is also sufficient to promote longevity in yeast, and adh-1 orthologs are induced in calorically restricted mice and humans, hinting at ADH-1 acting as an anti-aging effector across phyla.
AMAR is required for longevity across anti-aging interventions
AMAR is sufficient to promote longevity in C. elegans and yeast
AMAR extends lifespan, at least in part, by metabolizing glycerol
AMAR is activated in response to geroprotective interventions in mice and humans
This related research is also of interest, and given the first quote in this post of mine, suggests that exercise performance might be enhanced with rapamycin because of the effect rapamycin has in increasing ADH-1 levels…
Paracardial fat and vitamin A: a mechanism for regulating exercise performance
Petrosino et al. show that paracardial fat samples from older mice or mice fed a Western diet had decreased levels of alcohol dehydrogenase 1 (ADH1). Paracardial fat samples from humans with obesity also had decreased levels of ADH1 mRNA, supporting the translational relevance. Additional experiments with Adh1-KO mice and surgical fat transplantation experiments provide additional mechanistic insight. Paracardial fat may regulate exercise performance by altering circulating metabolites and/or endocrine effects. ADH1 appears to regulate the mitochondrial content of paracardial fat, a mechanism mediated by retinaldehyde. When ADH1 is active, the paracardial fat has characteristics of brown fat, which is beneficial for exercise performance. Further research is warranted to determine the translational potential of these findings, such as whether removing paracardial fat at the time of open-heart surgery might improve recovery time by increasing exercise capacity.
Does anyone know what these blood tests are?
Fatty acids are routinely checked during medical examinations, such as blood tests measuring your lipid profile. But clinicians and researchers often overlook the other key component of fat despite its potentially harmful effects: glycerol, a compound that links fatty acids to make a fat molecule.
The new post my be good to take a look at in tandem: