FAQs: Autophagy

  1. What role does autophagy play in improving the health of cells outside the nervous system and what do we know about its role with regard to the brain?

    Studies show that stimulation of autophagy is plays a vital role in the life prolongation achieved by calorie restriction in lower organisms such as yeast and worms. Many scientists suspect that a key mediator of the health benefits of prolonged calorie restriction in mammals is a preservation of the capacity for autophagy, at least outside the brain. Although fasting induces an acute increase in autophagy in most tissues, the more intriguing effect of long-term calorie restriction is to prevent an age-dependent reduction in basal or stimulated autophagy. No one seems to have a clue as to why this happens. It is clear that properly regulated autophagy (i.e. balanced by new synthesis of proteins and organelles such as mitochondria) helps to keep the interior of our cells “clean” and optimally functional by getting rid of proteins, aggregates of proteins, and organelles that have been damaged by oxidative stress or other mechanisms. By keeping our mitochondria in optimal working order, autophagy may help to control oxidative stress that contributes to mutagenesis and cancer. Theoretically, this could be valuable for preserving the functional status of our vital organs, particularly those with long-lived cells like our heart or skeletal muscles. Could shorter-term calorie restriction or fasting regimens have a “rejuvenative” effect on our organs via increased autophagy? This is an intriguing prospect, but so far little research in rodents or humans has addressed this possibility. Water fasting regimens of ten days or so appear to have some intriguing health benefits, but the extent to which these are mediated by autophagy is not clear.

    It is however very clear that an adequate basal level of autophagy in brain neurons is required to prevent neurodegenerative disorders — many of which are associated with and mediated by undue accumulation of toxic protein aggregates in neurons. Indeed, drugs which accelerate autophagy in the brain have been shown to be useful in rodent models of Alzheimer’s and Parkinson’s disease. Unfortunately, however, there is no consensus that calorie restriction or fasting is capable of activating brain autophagy; many scientists doubt this. One report indicates that a 48 hour fast activates brain autophagy in mice, but a similar study fails to support this; and no studies have examined the impact of calorie restriction protocols on brain autophagy. The good news is that, regardless of the impact of calorie restriction on brain autophagy, restriction exerts hermetic effects on the brain that boost the activity of neuronal growth factors and other proteins that can protect the brain from a wide range of stressors, and very likely provide some protection from our most common neurodegenerative disorders.

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