What does autophagy do against ageing and disease?
Autophagy is a genuine part of the ageing process and plays a role in many age-related diseases, but the translation into proven human interventions has not yet been made. What you can do now: exercising regularly, sleeping enough and fasting occasionally are the best-supported ways to keep this cellular system active.
Autophagy is your cells' waste-management system: damaged proteins and worn-out components are packaged up and broken down via lysosomes (a kind of cellular stomach). As you grow older, this system loses its power. Multiple review studies describe this decline as one of the central drivers of ageing, because the accumulation of cellular damage then accelerates.
Impaired autophagy has been linked to a broad range of age-related diseases: brain diseases such as Alzheimer's and Parkinson's, heart disease, diabetes and joint conditions. The association has been described consistently, but cause and effect are not always clear. In cancer the role is even ambiguous: autophagy can both suppress tumour growth and help cancer cells survive, depending on the stage of the disease. That makes it difficult to use autophagy as a straightforward therapeutic target.
In animal and laboratory research, well-functioning autophagy consistently extends lifespan. Whether that applies directly to humans has not yet been demonstrated, but the associations are comparable across yeast, worms, flies and mice.
The most concrete pointer to a practical handle comes from research into fasting and spermidine. Spermidine is a substance that occurs naturally in wheat germ, soya and cheese. Fasting raises spermidine levels, including in humans. Spermidine then promotes autophagy. In animal models, the protective effect of fasting on the heart and on joint inflammation disappeared as soon as spermidine synthesis was blocked. That points to a clear chain of events, but the translation into concrete health effects in humans has not yet been made.
Exercise, better sleep and lower calorie intake are described in review studies as ways to slow the age-related decline of autophagy. Large randomised trials in humans using hard endpoints are largely absent. Direct drugs that steer autophagy are under active investigation, but their safety and efficacy in humans have not yet been proven. One important note: several authors of these studies have commercial interests in companies developing this type of drug.
Based on multiple review studies and a mechanistic study in model organisms (yeast, worms, flies, mice) with additional small human data for spermidine/fasting. No large RCTs in humans using hard endpoints are available. Potential conflicts of interest have been reported for the pharmacological modulators.