By His Grace and Blessings, I write
Calorie Restrictions and Longevity
This blog is a continuation of my earlier discussion on role of calorie restrictions in enhancing longevity and promoting health-spans. I intend to take the reader through specific molecular and cellular mechanisms which are impacted by Calorie restrictions. Certain concepts like autophagy, sirtuins, mTOR, AMPK, ketones etc.will be introduced in this blog and further elaborated in my future discussions around issues of longevity and health-spans.
Hippocrates claimed that diseases are natural and not supernatural and many ailments are associated with gluttony. In a way overeating is the root cause of many bodily ailments as per the father of modern medicine.
According to David Sinclair, a Harvard Professor, “not eating stimulates proteins which are directly responsible for DNA repair. DNA damage is what causes ageing.”
Mark Mattson, a professor of neuroscience, claims that fasting promotes growth of new neurons in the brain and prevents neuro degenerative diseases.
The evidence from Blue zones also highlights importance of Calorie Restrictions as an important constituent in longevity of people. For instance, the Confucian adage of “Hara, Hatchie, Bu- diet is recited before eating by Okinawa people, reminding them to stop eating when they are 80% full. Similar kind of practices are followed in various other zones where people regularly fast.
A Buchinger Wilhelmi study published in PLOS ONE in 2019, revealed that 1422 patients who had undergone fasting and calorie restrictions for 4 to 22 days, showed significant impact on various health parameters like metabolism, BP, Glycemia, ketone bodies etc. Various studies proved that fasting takes body into regenerative and rejuvenative modes.
Cellular and Molecular mechanisms; Autophagy
As we age, protein and DNA get damaged due to various kinds of stresses-oxidative, glycated, reactive nitrogen etc. This dysfunctional DNA and cell damage needs to be removed quickly from the body. However, over a period of time the body loses the ability to remove the damaged cells.
In 2016, the Japanese scientist Yoshinori Ohsumi received Noble Prize for his discovery of the process of Autophagy. According to him, Autophagy is a natural, regulated mechanism of the cell that removes unnecessary or dysfunctional components. It allows the orderly degradation and recycling of cellular components. In simple words, autophagy is a process whereby the healthy cells use components of dead cells like amino acids etc. to feed themselves during the times of crisis. In this manner this process clears the body of the garbage of dead and dysfunctional cells which interfere with cell regeneration and thus cause ageing.
However, in our modern-day lifestyles with abundantly available food, the process of autophagy comes to a grinding halt. The simple reason is that our cells never get stressed due to prolonged hunger, and therefore don’t feel the need to munch upon our damaged and dead bodily cells. We are constantly eating under 3 meal paradigms of American diets. Fasting and calorie restriction is what actually activates autophagy.
When we don’t eat for a longer time or restrict the calorie intake, we enhance production of ketones in the body. These ketones then use our stored fats instead of glucose and proteins which are in short supply due to fasting. Keto diets are the diets which are low on glucose, carbohydrates and protein but high on fats.
Sujata: The Buddha’s Last Teacher, Buddha fasted for a very long time and was then offered food. It is believed that Buddha got enlightend that very night ….
Evolutionary our bodies are made to sustain more on fats then on proteins or carbohydrates. This can be gauged from the fact that our bodies have evolved to store fat and not proteins and sugar. By fasting we tap into fat stores of our bodies for energy, while our protein requirement is met through the autophagy process. A relevant question that is raked up by some experts is that fasting or calorie restriction is not good because it lowers metabolism and eats into our lean mass/ muscle mass. The same doesn’t stand to reason after discovery of the process of autophagy which clearly establishes that during fasting, there is little change in our metabolism and our newer and healthier cells utilize waste from dead cells and take very little from our muscle mass.
mTOR: mammalian Target of Rapamycin
A very important process in autophagy activation is mTOR. It’s a pathway, a master controller of protein synthesis. When its high it promotes growth in the body. When it is low, it helps in repair and maintenance of cells through autophagy. As we age, we need mTOR more for repair and maintenance functions and less for growth. Chronic overexpression of mTOR is linked with premature ageing and disease. Hence lower intake of calories decreases glucose and protein levels, thus reducing mTOR and stimulating autophagy. Exercise enhances autophagy in humans.
AMPK; Activated protein kinase
AMPK is a signaling pathway, a master regulator of energy metabolism in the cell. It inactivates mTOR and through ULK-1 protein activates autophagy pathways. Exercise promotes AMPK in the body.
Research has established that AMPK and mTOR are the key switches that ultimately guide autophagy and govern whether or not we are going to tear down/break down abrupt and dysfunctional cells. It has been further shown that our metabolism and cell mechanisms inside the cells are influenced by our circadian rhythms. Eating at the same time everyday changes mTOR expression and eating earlier is generally better.
Disclaimer: the above shall not be construed as a medical advice . one should consult a doctor before implementing any of the suggestions as made above.
To be continued……
By His Grace and Blessings, I write….
Dr. Seema Chaudhary