Arguably, the most important driver of aging is the decline in autophagy, the cellular self-cleansing process that rids cells of junk.
Aging just is damage, yet at younger ages, both humans and animals are capable of clearing up the damage and renewing their tissues. They do this through autophagy, which regularly turns over — that is, breaks down — proteins, organelles, and other damaged cellular constituents. 1
The process of ageing denotes a post-maturational deterioration of cells and organisms with the passage of time, an increased vulnerability to challenges and prevalence of age-associated diseases, and a decreased ability to survive. Causes may be found in an enhanced production of reactive oxygen species (ROS) and oxidative damage and not completed housekeeping, with an accumulation of altered ROS-hypergenerating organelles in older cells. It has been shown that autophagy is the only tier of defence against the accumulation of effete mitochondria and peroxisomes; that functioning of autophagy declines with increasing age and determines cell and individual lifespan; that autophagy can be intensified by drugs; and that the pharmacological intensification of autophagy may be a big step towards retardation of ageing and prevention and therapy of age-associated diseases including neurodegeneration.
Calorie restriction, the most robust life-extension intervention known, requires autophagy to work. 2
So at least one thing that calorie restriction does to extend lifespan is increase autophagy. When animals lack food, autophagy ramps up to increase the supply of nutrients, especially amino acids, which it gets from breaking down cellular waste.
Other interventions that increase lifespan also appear to depend on increased autophagy. For example, FIRKO — fat insulin receptor knockout — mice have extended lifespan. These mice lack an insulin receptor in adipose tissue. 3
Among the consequences of lacking an insulin receptor in fat tissue is a 60% reduction in that tissue, leading to 20% lower body weight, while calories ingested were more than 50% greater than controls. 4
Wait a minute. These animals ate a lot more than controls but also lived longer. What about calorie restriction?
These animals have lower insulin levels, and that leads to higher levels of autophagy. 5
Increased autophagy allows these animals to clear damage more effectively and thus to live longer.
One of the main themes of my book Stop the Clock is that living longer and in good health requires that you counteract the decline in autophagy that happens to everyone as they age.
How do you increase autophagy?
Another interesting way to stimulate autophagy and extend lifespan uses the drug Acipimox, a derivative of niacin. 6
Acipimox does the same thing as niacin, only with less of a flushing effect, which puts many niacin users off. Unfortunately, it appears that Acipimox is not available in the U.S., so niacin must be used if you live here.
In rats, fasting once weekly and receiving Acipimox on the day of the fast was as effective in increasing autophagy to youthful levels as fasting every other day without the drug. 7
Huge, if you ask me. Every other day fasting is a strenuous burden unlikely to be embraced by most people (like me). But fasting once a week and taking Acipimox is just as effective and much more doable.
Furthermore, niacin ought to be equally effective.
I tried this yesterday. About 16 hours into what proved to be an 18-hour fast, I took a 500 mg tab of extended-release niacin. I has quite a bit of flushing and itching, and while not disastrous or painful, it’s kind of unpleasant.
Supposedly, the flushing goes away with continued use.
Intermittent fasting may be the strongest, most effective anti-aging intervention we currently have. The logic behind this reasoning is that it does the same thing that calorie restriction does in terms of physiology, and calorie restriction is the most effective anti-aging intervention in lab animals.
Boosting the physiological effects of intermittent fasting with the substances noted above should make it even more effective.
Intermittent fasting directly counteracts the mechanism of aging.
PS: Check out my book, Stop the Clock, for much more on how to fight aging.
PPS: Check out my Supplements Buying Guide for Men, where you’ll find some of these autophagy boosters.