Autophagy again - promoted by exercise

I've referenced autophagy before in relation to fasting.  Scientific American today pointed to a new study in Nature which identifies exercise induced autophagy.

“Our findings demonstrate that exercise is a potent inducer of autophagy,” the researchers wrote. “Autophagy induction may contribute to the beneficial metabolic effects of exercise,” they concluded.

 Here is the abstract - Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis

Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes1. However, the cellular mechanisms underlying these effects are incompletely understood. The lysosomal degradation pathway, autophagy, is an intracellular recycling system that functions during basal conditions in organelle and protein quality control2. During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism3. Moreover, in animal models, autophagy protects against diseases such as cancer, neurodegenerative disorders, infections, inflammatory diseases, ageing and insulin resistance4, 5, 6. Here we show that acute exercise induces autophagy in skeletal and cardiac muscle of fed mice. To investigate the role of exercise-mediated autophagy in vivo, we generated mutant mice that show normal levels of basal autophagy but are deficient in stimulus (exercise- or starvation)-induced autophagy. These mice (termed BCL2 AAA mice) contain knock-in mutations in BCL2 phosphorylation sites (Thr69Ala, Ser70Ala and Ser84Ala) that prevent stimulus-induced disruption of the BCL2–beclin-1 complex and autophagy activation. BCL2 AAA mice show decreased endurance and altered glucose metabolism during acute exercise, as well as impaired chronic exercise-mediated protection against high-fat-diet-induced glucose intolerance. Thus, exercise induces autophagy, BCL2 is a crucial regulator of exercise- (and starvation)-induced autophagy in vivo, and autophagy induction may contribute to the beneficial metabolic effects of exercise.

Chronic Cardio is healthy?

In our little paleosphere endurance exercise is usually characterised as a "bad" thing.  Mark Sission's Chronic Cardio post is the usual basis for all this, but there are other references too.  In general I agree with this view.  However sometimes other bits and pieces pop up that indicate a different viewpoint.  I saw this one the other day:

Autophagy-related and autophagy-regulatory genes are induced in human muscle after ultraendurance exercise

The purpose of this study was to evaluate whether ultra endurance exercise changes the mRNA levels of the autophagy-related and autophagy-regulatory genes. Eight men (44 ± 1 years, range: 38–50 years) took part in a 200-km running race. The average running time was 28 h 03 min ± 2 h 01 min (range: 22 h 15 min–35 h 04 min). A muscle sample was taken from the vastus lateralis 2 weeks prior to the race and 3 h after arrival. Gene expression was assessed by RT-qPCR. Transcript levels of autophagy-related genes were increased by 49% for ATG4b (P = 0.025), 57% for ATG12 (P = 0.013), 286% for Gabarapl1 (P = 0.008) and 103% for LC3b (P = 0.011). The lysosomal enzyme cathepsin L mRNA was upregulated by 123% (P = 0.003). Similarly, transcript levels of the autophagy-regulatory genes BNIP3 and BNIP3l were both increased by 113% (P = 0.031 and P = 0.007, respectively). Since upregulation of these genes has been related with an increased autophagic flux in various models, our results strongly suggest that autophagy is activated in response to ultra endurance exercise.

Autophagy is usually presented as a "good thing" - the self eating process by which cells clean themselves up, getting rid of waste products and some pathogens.  Often it is promoted by fasting and again in the paleo world it is one of the benefits that are claimed for intermittent fasting.  I've probably written about that in the past somewhere.

Anyway, this study seems to link it to ultraendurance exercise.....actually it is talking epigenetics as far as I can see, particular autophagy related genes being switched on.  I suppose this might make sense if the exercise has actually cause massive damage and the body is frantically trying to clear up and repair the mess.  Maybe not so positive.

Self Eating.....not a bizarre form of masturbation

Autophagy (surely pronounced Auto[space]Phagy) is usually characterised as cells eating themselves.  I think I've posted stuff before about  autophagy being turned on by fasting.   This guy (Ron Mignery) also explains how fasting from protein alone can also turn on autophagy.   Matt Lalonde also mentioned this idea in Robb Wolf's podcast last week - he occasionally has a low protein dinner to promote autophagy.

Anyway, here is something else interesting - another reason to fast occasionally or at least have low protein days - autophagy represents an important natural safeguard against cancer development:


Scientists discover that self-eating cells safeguard against cancer

Normally, the process of autophagy is switched on when cells experience periods of starvation and in this context is beneficial by helping to keep the 'wolf from the door' until food reappears on the menu. However, the Martin laboratory has discovered that mutations in a gene called Ras, which is involved in approximately 30% of human cancers, triggers excessive autophagy leading to auto-destruction of the fledgling tumour cell. Mutant Ras was found to switch cells into the self-eating mode by ramping up the production of Noxa. The study suggests that autophagy represents an important natural safeguard against cancer development.