Fasting and calorie restriction have a lot of positive data. Not only in peer-reviewed "western" research, in recent decades, but going back centuries in religious traditions. It is free, effective, and safe. Humans can easily "physically" fast for 1 to 3 days with hardly any negative side effects in the known literature. We are adapted to do this. We evolved to do this.
That being said, it is the mental part of fasting that prevents people from using this powerful method of true short-term rejuvenation. That is why obese people in western nations prefer taking supplements. It is easier. People think they can eat garbage and then take a few supplements to make it all better. I am not going to list references, but it is my observation that supplements have only small effects in reducing the rate of aging. Most are probably not worth it. I say this, even though I take quite a few. I am probably wasting money for the most part.
There is this natural and evolutionary mechanism of caloric restriction. I think it activates SIRT1, SIRT3, and SIRT6 sirtuins. This increases autophagy, cellular repair, and also has some senolytic effect. Obviously, all this intensified repair activity consumes more NAD+.
- In the old world, people benefited from caloric restriction, but suffered more nutritional deficiencies. Sometimes lethal.
- In the modern world, people experience few severe nutritional deficiencies, but poison themselves with junk food abuse (without even realizing it).
But... according to studies, giving resveratrol (direct or indirect SIRT1 activator) to mice on a high-fat diet made their health better, similar to that of mice on caloric restriction. Although caloric restriction seems to be more potent.
I don't need to give references, this was clearly shown years ago, when this supplement gained fame. Then its fame waned, I suppose because there are companies that want to advertise and sell other new things.
Sometimes, I think we are going around in circles around the existing sirtuin mechanism, optimizing this mechanism.
Example: quercetin (senolytic) is a SIRT1 activator.