Graeme Jones

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Protein and Calorie Restriction – The Key To Healthy Aging?

Research into the biology of aging has grown immensely in the last decade in our search for answers about longevity. The use of model organisms such as mice gives us tremendous insight into how we age, and the factors that accelerate or slow down the pace of the process.

Early research pinpointed calorie restriction as a potent therapy for extending the lifespan of many model organisms and delaying the age-related decline of function. However, let’s face it, for most of us restricting calories is difficult and not so enjoyable. We all know someone who gets ‘hangry’. We can often feel cold when hungry and eating out or with friends becomes difficult. However, diets like the 5:2 approach have made it at least a little more achievable and realistic. Whether they are sufficient enough is another question.

In the last blog ( https://foodpharmacy.se/2020/07/the-nine-cellular-hallmarks-of-aging/ ) I covered the 9 hallmarks of aging at the cellular level and how they speed up our demise and can give us grey hair
earlier in life, along with other more serious conditions. This is an essential piece of the puzzle in unraveling how calorie restriction, or any other therapy, works to promote healthy aging. This has led to the discovery of several important pathways for healthy aging that we can aim to target to slow our biological aging rate and reduce our risk of chronic disease developing early.

Of the different aging pathways, none is more heavily studied than a pathway called mammalian target of rapamycin (yes, a bit of a mouthful), or mTOR for short. It is named after the drug called rapamycin
which targets it. mTOR acts as a nutrient sensing pathway, meaning it is activated or inhibited by the level of nutrients entering your body from the food you eat. It functions as a switch between anabolic, or processes that build up the body, and catabolic, processes that break down the body. By inhibiting mTOR it universally extends lifespan in all model organisms, and thus has attracted lots of attention – if you can slow mTOR, you can live longer!

mTOR and lifespan

Within the cell mTOR primarily senses amino acid availability (1). In other words, mTOR senses how much protein is around to be used. When amino acids and/or ATP (the basic energy molecule we need to fuel our cells) levels are adequate, activation of mTOR promotes growth-related processes. This
means it is time for the body to build, grow and develop. But when amino acids (protein) and/or ATP levels are low, mTOR is inhibited. This promotes catabolic processes such as autophagy, which means asort of recycling of the parts of the cell that are broken.

With mTOR, it’s all about balance. Availability of amino acids promotes growth by activating mTOR, which helps us maintain muscle mass as we age. Body builders for example, are excellent at activating
mTOR through high protein diets and weight training. However, it can also promote cancer if activated too much over a long period of time. On the one hand, inhibiting mTOR promotes autophagy, which is very much needed in periods to remove and repair broken parts in our cells. But on the other hand if activated too often, it can also lead to frailty, which can cause major injury and be life-threatening.

Just to be clear, both rapamycin, a medical drug, and calorie restriction/fasting work by inhibiting mTOR
and therefore extending lifespan. And in general, most chronic disease is driven by chronic activation of mTOR. So science has shown us that manipulation of mTOR via calorie restriction, protein restriction,
and rapamycin, promotes lifespan and has a positive impact on all 9 hallmarks of cellular aging (3). It is however important to point out that this is often in comparison to animals made obese with a diet and lifestyle much like our own. Thus, it’s likely that a westernised lifestyle promotes an imbalance favoring mTOR activation.

Inhibiting mTOR seems to extend lifespan, but a balance is important for healthy aging

The mTOR pathway is a pathway that promotes healthy aging. Inhibition of mTOR in model organism living a western lifestyle leads to improvements in both healthspan (the quality of life) and lifespan (the length of life). But again, it’s about balance!

While calorie restriction inhibits mTOR, exercise activates it. With respect to promoting a long and healthy life, both calorie restriction and exercise are potent promoters of healthy aging. But too much calorie restriction to the point of nutritional deficiency, or too little exercise resulting in a loss of muscle mass, speeds up aging and chronic disease despite having inhibitory effects on mTOR.

The fact that inhibiting mTOR extends lifespan in model organisms subjected to a western lifestyle implies that our lifestyle does not promote such a balance. In our life, we can achieve this balance by
exercising regularly, eating a nutritious diet, and maintaining a healthy weight. Our exercise routine should contain both strength training and cardiovascular workouts to maintain muscle mass and fitness,
both essential to longevity. Our diets should also contain enough protein (to also retain muscle mass) and nutrients such as vitamins and minerals, but also have periods of calorie and protein restriction.
Look out for future blogs explaining how to apply this practically.


  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611156/
  2. https://www.nature.com/articles/nrm3522
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600378/

This is a guest post. The opinions expressed are the writer’s own.




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