Autophagy - keeping us fit through our senior years.

Exercise intensity

Exercise intensity is a measure of how hard you are working during a workout. There are different ways of measuring exercise intensity including the "talk test" for aerobic activities, using a "rate of perceived exertion" (RPE scales) and heart rate. With the integration of heart rate monitors into even the cheapest fitness tracker, heart rate monitoring is the most convenient measure of exercise intensity. 

Exercise with an elevated heart rate of at least 30 minutes per day in the MVPA zone (>64% of your maximum heart rate) is recommended as being good for your cardiorespiratory fitness. 

A minimum of 30 minutes per day in the MVPA zone may also help you stay young!

Autophagy means self-eating. 

The body eats itself. Sounds frightening?

In fact autophagy is an essential cellular activity.  A decline in our ability to maintain autophagy is a sign of aging. 

 There are different types of autophagy. (I will only mention macroautophagy, mitophagy and lipophagy). Each type of autophagy plays an important role in ensuring that our organs and tissues continue to function well. 

Macroautophagy

Macroautophagy (or commonly referred to as "autophagy") plays an essential role in clearing out "senescent" cells from our body. 

Senescent cells are cells which have lost their function but still remain within our tissues and organs. They have been referred to as "vampire cells" - sucking out our body's resources. As we age, senescent cells (including senescent stem cells) accumulate causing us to lose our ability to function and repair our tissues.

When macroautophagy fails to effectively remove senescent cells, the symptoms of age-related diseases such as frailty and its associated syndromes - sarcopenia (muscle loss), loss of immune response (and increased susceptibility to disease), loss of physiological functioning and dementia will develop. 

With the correct signals, we can enable macroautophagy to continue into old age, enabling our our body to remove and replace senescent cells, with healthy cells, allowing us to repair and function into old age. (More later)

Mitophagy

Mitophagy is a type of autophagy in which non-functioning "mitochondria" are replaced inside our cells. Our mitochondria serve many important functions, including aerobic energy generation, amino acid synthesis and iron metabolism.

Our muscle fibres are giant cells with many mitochondria. One mechanism for muscle growth requires  muscle stem cells to donate their mitochondria and nuclei to the muscle fibres. Mitophagy aids in to the growth and repair of these tissues.

Likewise the cells in many parts of our brain are energy hungry and also contain high levels of mitochondria. 

A failing mitophagic system will lead to weakness in our heart and skeletal muscles and in cognitive systems  

Lipophagy

A 3rd type of autophagy is lipophagy.

Lipophagy means eat lipids (or fats). We use lipophagy to break down lipid droplets inside our fat cells to release fatty acids for the body's energy metabolism. Lipophagy is also important in clearing fat deposits from within our skeletal muscle cells.

A faulty lipophagy system is associated with fat accumulation in the liver (leading to non-alcoholic fatty liver disease), atherosclerosis as well as a number of other physiological diseases.

Maintaining autophagy in our senior years

As we age, our cells' ability to facilitate autophagy declines. This decline is linked to the development of chronic inflammation which develops as we age. 

As a result, senescent cells accumulate in our tissues, sarcopenia, dementia and frailty set in, our immunity to diseases reduces and we begin to suffer a range of physiological abnormalities. 

However, the good news is that declines in macroautophagy, mitophagy and lipophagy can be arrested and even reversed through exercise, a calorie restricted diet and perhaps pharmaceutical or nutriceutical supplementation.

The key appears to be ensuring that our body undergoes acute bouts of stress; for example, through anaerobic metabolism and lactic acid accumulation and/or calorie restriction. 

So, in essence - "acute" (short term) inflammation induced by exercise helps to overcome the  effects of chronic (long term) inflammation.

Which type of exercise is good for autophagy?

There is no clear evidence as to which type of exercise is best for autophagy. Research suggests that resistance training, endurance training and HIIT are effective in activating autophagy. 

The intensity and type of resistance training will have a significant bearing on how well autophagy is activated in seniors. Overloading your muscles will help provide the necessary stress and also help to build your muscles, which also triggers a reduction in chronic stress.

Acute bouts of exercise (including HIIT!)  causes acute inflammation/stress due to the development of anaerobiosis in the muscles and accumulation of lactate in the tissues. This stress, in turn, initiates events which activate different forms of autophagy throughout our body. 

Endurance training if performed with a reasonable level of intensity will cause stress and deplete the body's glycogen stores (which appears to be an important trigger for autophagy). Gentle walking would however, not provide the same autophagic triggers as a 5km run. 

Likewise lifting a 2kg dumbbell, would not be as effective as a set of 10 or 15 x 20kg dumbbells lifts with isometric holds.

Summary

Macroautophagy, mitophagy and lipophagy are important types of autophagy.

HIIT, resistance training and endurance training as well as calorie restricted diets appear to be effective in ensuring that our autophagic systems stay active in old age. The level of intensity appears to be a key factor in determining the effectiveness of the exercise.

Want to know more?

This article from Nature Aging provides an in-depth review of autophagy