The Health Improving Effects of Aspirin Depend on Autophagy

Top rated Nutritional supplements in support of Nitric Oxide Health

Seeking top-quality recognised supplements?  Learn about  Cardio Cocktail Endorsed Supplements.

Many groups are attempting to develop calorie restriction mimetic drugs that produce benefits to health - and slow the progression of aging - by triggering some fraction of the stress response mechanisms engaged by the practice of calorie restriction. The most notable such mechanism is autophagy, a collection of cellular housekeeping processes that recycle damaged proteins and structures in the cell. Greater efficiency or activation of autophagy is a feature of a great many interventions known to slow aging in laboratory species.

Based on existing data, we should not expect any of these therapies to move the needle all that far on human life span, however. We have the example of calorie restriction, for which the health effects are fairly well known in human subjects. We also have aspirin, which is a calorie restriction mimetic, and is the subject of many very large human studies. Neither does all that much for life span in the grand scheme of things; a few years here, a few years there. We simply cannot expect novel calorie restriction mimetics to do more than modestly improve health and modestly reduce mortality, given this wealth of existing data that establishes the bounds of the possible for this approach to the treatment of aging.

Autophagy-mediated metabolic effects of aspirin

Aspirin is one of the oldest molecules to be used as a chemically defined entity for the treatment of human disease. Indeed, salicylate and its derivatives contained in plant extracts have been used since Mesopotamian times. As true for many other pharmaceutical agents, the effects of aspirin have been determined empirically to include anti-inflammatory, analgesic, and thrombosis-preventive effects before a molecular mode of action would have been postulated

Here, we investigated the metabolic effects of aspirin on the extracellular (plasma) and intracellular metabolome in mice by comparing them with those elicited by fasting. We and others have previously demonstrated that fasting or other caloric restriction mimetics than aspirin (such as spermidine and resveratrol) induce a broad deacetylation of multiple proteins involved in the regulation or execution of autophagy. We show that aspirin induces metabolic changes that are commensurate with the alterations produced by nutrient starvation, that it can indeed cause protein deacetylation in circulating white blood cells, that it inhibits EP300 but also other protein acetyltransferases, and that it mediates its positive metabolic effects through the induction of autophagy.

Indeed, the capacity of aspirin to reduce dietary adiposity, diabetes, and hepatosteatosis, as well as to enhance the efficacy of immunogenic chemotherapeutics, was lost in two distinct genetic mouse models of autophagy deficiency, as well as upon knockdown of Atg5 autophagy gene in cancer cells, respectively. Hence, the health-improving effects of aspirin depend on autophagy.

Learn more about Nitric Oxide Supplement and Cardio physical health.

source https://www.fightaging.org/archives/2020/12/the-health-improving-effects-of-aspirin-depend-on-autophagy/