Oxidative ageing: from proximate to ultimate causes

Oxidative stress seems really important in age-related decline and disease—but what causes it? Here I’ve tried to express a broadening perspective, by exploring its core, context and ultimate causes; and largely anchored in human studies where possible.

We all die—what matters is how. While human life expectancy has increased, non-communicable diseases are now the major cause of disability and death globally (WHO and OWID). These are mostly age-related diseases (e.g. CVD, cancer, COPD, dementia, etc.), which develop slowly over time, and coexist as multimorbidity (e.g. most people >65 in US/UK ^1,2); resulting in functional decline/frailty and socioeconomic burden (i.e. ↓ productivity, ↑ sick care). This situation is growing globally, as populations are ageing, and diseases occur earlier—so we may live longer but sicker ¹. Moreover, this invisible epidemic underlies susceptibility to (communicable) infectious diseases, such as COVID-19 ³, elevating chronic disease to acute threat.

Chocolate vs. CFS: flavanols and beyond

There have now been several preliminary studies testing the effects of phytochemical-rich plants in ME/CFS, some of which show benefit (discussed later). Of these, I find the 2010 trial with chocolate particularly intriguing ¹.

This was a very small pilot trial (UK, n=10 CFS, Fukuda criteria + severe fatigue; no mood disorders, no drugs) to test the effect of polyphenol-rich chocolate for 8 weeks on symptoms. It had a double-blind, placebo-controlled, crossover design (8–2–8), with several subjective outcomes; and high methodological quality in a recent systematic review ². The active treatment arm had an improvement in fatigue, anxiety, depression and disability (pre–post effect: –35%, –37%, –45% and +31%, respectively); anecdotally, 2 people with short illness duration even returned to work ¹. For reference, this is a greater reduction in fatigue, depression and anxiety than over a year of CBT or GET in the large PACE trial (UK, n=641 CFS, multiple criteria), which used some of the same outcome measures ³.

Salicylic acid: are we already taking aspirin?

Salicylic acid has a long history of use in medicine. Nowadays it’s a common ingredient in many skincare products and central component of the anti-inflammatory drugs aspirin (acetylsalicylic acid, ASA) and mesalazine (5-aminosalicylic acid, 5-ASA). Major pharmacological targets of salicylic acid include inhibition of COX (inflammation) and activation of AMPK (energy homeostasis).

Perhaps less well known, is that salicylic acid is a natural phenolic molecule widely distributed throughout nature. Salicylic acid is present in many plants; the name derives from the willow tree (Latin Salix) where it was originally obtained. Low levels of salicylic acid are also already present in the blood of animals, both carnivores and herbivores, some of which may come from internal biosynthesis and the rest from diet ¹.

Contrabiotics block intestinal pathogens

Foods can beneficially shape the gut microbiota through their prebiotic or antibiotic/antimicrobial effects. On the other hand some food components are able to block the adhesion and invasion of undesirable bacteria, thereby promoting their passage out the gut, and these have recently been termed contrabiotics ¹. Contrabiotics have their most obvious application with infectious diarrhea and inflammatory bowel disease, but might also have some relevance in general dysbiosis and small intestinal bacterial overgrowth (SIBO).

Carotenoids and skin colour: a redox-dependent display of health?

There has been some interesting research recently on carotenoids and skin colour ^1–3, which has also made it into the mainstream media. The potential links between carotenoids, skin colour and health intrigue me, as explained below.