Most of us who are into health and fitness also want to know how we can inhibit the aging process, so as to have a healthy old age free of illness, and hopefully live a long time. We’re aware of the usual healthy practices such as clean diet, exercise, a good night’s sleep, limiting the use of alcohol, ensuring we’re well nourished with vitamins, and so on. But we still age. What further measures can we take to slow aging? What’s the optimal anti-aging strategy?
The process I’m going to write about here is not merely an addendum to a healthy diet, exercise, and so on. It is likely as important or more so than those.
This strategy is based on the critical knowledge that exceptionally long-lived lab animals, those that have lifespans that are double and more than those of the shorter-lived varieties, have mutations that increase the process of autophagy. Autophagy is the process of cellular “self-eating” that occurs in all animals regularly, and is increased by fasting. In aging, cellular “junk”, such as malfunctioning mitochondria, misfolded proteins, and damaged organelles accumulate, causing the maladies of aging. But this junk accumulates precisely because the organism is unable to initiate and maintain autophagy.
These mutant animals that live twice as long or more than normal animals do eventually die. But the fact that increased autophagy extends their lives shows that it is the most important, the limiting factor in lifespan.
In virtually all organisms tested so far, and there’s no reason to believe that humans are an exception, calorie restriction (CR) extends lifespan, often dramatically. But why does CR do this? In the worm C. elegans, autophagy is required for lifespan extension from CR.
Dietary restriction extends life span in diverse species including Canorhabditis elegans. However, the downstream cellular targets regulated by dietary restriction are largely unknown. Autophagy, an evolutionary conserved lysosomal degradation pathway, is induced under starvation conditions and regulates life span in insulin signaling C. elegans mutants. We now report that two essential autophagy genes (bec-1 and Ce-atg7) are required for the longevity phenotype of the C. elegans dietary restriction mutant (eat-2ad1113) animals. Thus, we propose that autophagy mediates the effect, not only of insulin signaling, but also of dietary restriction on the regulation of C. elegans life span. Since autophagy and longevity control are highly conserved from C. elegans to mammals, a similar role for autophagy in dietary restriction-mediated life span extension may also exist in mammals.
In a review, Autophagy and Aging, the authors state:
Genetic inhibition of autophagy induces degenerative changes in mammalian tissues that resemble those associated with aging, and normal and pathological aging are often associated with a reduced autophagic potential. Pharmacological or genetic manipulations that increase life span in model organisms often stimulate autophagy, and its inhibition compromises the longevity-promoting effects of caloric restriction… Here, we discuss the probable cause and effect relationship between perturbed autophagy and aging, as well as possible molecular mechanisms that may mediate the anti-aging effects of autophagy.
I included excerpts from both of these articles to emphasize how central autophagy is to aging. Many other treatments besides CR that slow aging and extend life, such as lithium and resveratrol, appear to work by enhancing autophagy.
The mitochondrial theory of aging attempts to account for aging by the increased number of damaged, malfunctioning, and free-radical-producing mitochondria. However, under normal, healthy conditions, autophagy removes and recycles these mitochondria, so a more fundamental reason for aging is deranged, that is repressed, autophagy.
Normally, autophagy in humans rises and declines with a strong daily rhythm. Since autophagy is upregulated by fasting (or starvation), it strongly increases at night and in the early morning, since no food is taken during the night. During the day, during the fed state, autophagy proceeds at a low, basal level.
Humans and other organisms exhibit a strong diurnal rhythm of anabolism and catabolism. Both are equally necessary to life and health. With aging, however, that rhythm declines in amplitude. At night, when autophagy should be strongly activated, it is only weakly so or not at all. In the day, when anabolism should be at full speed, aging weakens the process. This is known as anabolic resistance.
Also due to the diurnal or circadian rhythm in autophagy, levels of glutathione, a tripeptide that is the body’s most important antioxidant, rises and falls. The liver, for example, may contain as much as 100% more glutathione during the day as in the early morning.
As a consequence of the age-related decline in autophagy, the amino acids that are necessary for the synthesis of glutathione fall, and not enough glutathione is produced. Since glutathione is an important antioxidant, if cells don’t make enough, free radicals become abundant and a state of oxidative stress ensues, which is a hallmark of aging. Not good. Oxidative stress in turn causes autophagy to decline, so we have a vicious cycle of less autophagy, more oxidative stress, even less autophagy, and so on.
Now, sarcopenia, or muscle wasting, is also characteristic of aging, and anabolic resistance causes it. Maintaining a healthy amount of muscle mass is crucial to healthy aging and longevity. This healthy amount of muscle mass also decreases oxidative stress, since muscle is the main source through which autophagy releases amino acids, and thus synthesizes glutathione.
The key: to avoid aging, one must go through periods of time of a strong breakdown in tissue (autophagy), followed by a rigorous building up again of the same tissue (anabolism). In this way, the body is rejuvenated, since the tissues that are broken down are old, damaged mitochondria, misfolded proteins, and other cellular debris.
By now you’re probably wondering how to do this, and the answer is very simple. Here’s the equation for living a long time: fasting for a time followed by weightlifting + protein = longer life.
I’m dead serious about this. If you fast, you increase autophagy, which rids your cells of junk. But you must follow this by anabolism, and the best way to accomplish this, even if you’re old, is by lifting weights and eating enough protein.
Ideally, one wants to take protein around workouts, and whey protein has been shown to give the best anabolism bang for the buck. It causes amino acid levels to rise rapidly in the blood, which ensures maximum anabolism. Whey also has the additional benefit of being rich in cysteine, which is the rate-limiting factor in glutathione synthesis. Thus whey can increase levels of glutathione, and this is especially beneficial in older people. And you thought it was only good for bodybuilders.
Whey can also be taken with benefit by older people in the morning. The cysteine and other amino acids in whey will help replenish glutathione, and so lower oxidative stress. Alternatively, n-acetylcysteine, a source of cysteine, may be beneficial for this, and should be taken with the first meal of the day to ensure that other amino acids are present.
As for fasting, well, we’ve discussed intermittent fasting a lot around here. Fasting is crucial to maintaining a high level of autophagy as we grow older. A 12-hour fast, between dinner and breakfast, will likely suffice for those not too old. An even healthier practice might be a daily feeding window of 8 to 10 hours, and during the rest of the time not eating at all. (Exercise should of course be done during the feeding phase.) Eating late at night – or in the middle of the night – is to be strongly discouraged, as this is when you want autophagy going full blast.