Last week, an article about the cell biology of fasting made headlines in the science news press. Valter Longo cites evidence that a 3-day fast can rejuvenate our immune systems, with broad anti-aging benefits. 4 or 5 days may be better yet.
Socially, I was a late bloomer socially, clinging too tightly to love, driving away partners until I was in my 20's. I took a full year to allow Marsha into my heart. Four years later, she broke up with me, and it launched a full-scale spiritual crisis, beginning with three days in which I had no interest in eating.
Those of you who have probed my Aging Advice page know that I fast a day a week, water only from Wednesday evening to Friday morning. I have grown quite comfortable with this routine. I ease off other disciplines on Thursdays, take a day off from aerobic exercise, allow myself to sleep more and be less productive. I still do yoga, and like to take long walks on Thursdays.
But not since I was 28 have I fasted three days. Monday morning, I awoke with the thought that this is as good a time as any to begin a three-day fast. If I wait longer, I will have time for fear and worry. My mind will play tricks on me, making it harder than it has to be.
I first became acquainted with Valter Longo's work when, in 2004, he published a remarkable paper in Journal of Cell Biology based on work he did on yeast cells for his dissertation almost a decade earlier. The results were considered so unlikely that it had taken him that long to convince a journal editor to take a chance and publish them. What Longo had discovered was that when he starved a colony of yeast cells, about 95% of the cells would commit suicide, using the controlled death mechanism of apoptosis. They would disassemble their proteins, dissolve the cell membranes, and turn themselves into food for the remaining 5%.
Impossible! replied the reviewers, schooled in traditional evolutionary theory. How could such an adaptation evolve? The colony must be closely related genetically, and how could the 5% be genetically different from the other 95%? And whatever that difference was, the 5% would pass on their genes, the genes of the 95% would perish, and the next generation would no longer have the suicide adaptation. We know this from basic theory, said the reviewers. Longo must have made a mistake in his biochemistry. These cells are not committing suicide -- they are starving to death.
"Extraordinary claims require extraordinary evidence. *" The paper was returned to him over and over, demanding more and more validation that what he saw was really apoptosis. It took ten years before the paper was finally accepted for publication.
Today the fact that Longo discovered is widely accepted, though the message for evolutionary theory has yet to filter through. But Valter saw the full implication of his work: If yeast cells had failed to read the basic textbooks in population genetics, what other animals and plants might have been similarly negligent? Yeast cells are just one example of programmed death in the biosphere. I was honored and excited the following year when Valter invited me to join him and Vladimir Skulachev in a paper for Nature Genetics on Programmed and Altruistic Aging.
In the intervening decade, Valter has been a ubiquitous presence in the biology of aging and of caloric restriction. Of many creative innovations he has introduced, the one he is best know for is fasting as a cancer treatment. He has documented that a three-day fast before chemotherapy has a powerful and extraordinary effect on the metabolism: The body's normal cells are in a heightened state of protection, and are much more resistant to chemical toxins. Hence the discomfort, headaches and nausea that generally accompany chemotherapy are attenuated -- not to mention the long-term damage. At the same time, the cancer cells are sensitized by the fast, so that more of them are knocked out by the chemo treatment. This is a win-win for the patient, but Valter has undertaken a long and arduous campaign to convince oncologists that such a simple protocol could be so effective. Worst of all, no one can make a dollar from fasting.
And what of the rest of us, who don't have cancer? This is the subject of Valter's most recent work, that made science news headlines last week. He puts together evidence from mice and humans that the three-day fast is a boon for us as well. (Here is the full text, and here is an editorial in the same issue of Cell Stem Cell putting the article in context.)
Evidence in this week's Longo Article
The experiment around which the paper is written involves depriving mice of food, then looking at the stem cell environment in their bone marrow. Fasting actually increases the number of active stem cells in the bone marrow, even as the circulating white blood count is down sharply. Two chemical signals are identified that mediate the process: Both IGF-1 and PKA are down-regulated with fasting.
IGF-1 (insulin-like growth factor) is an old friend, first discovered in worms in the 1990s, and later identified as a pro-aging hormone generally. PKA (protein kinase A) is less well known, and has many independent functions, de-activating several different signals by tacking on a phosphate group. The cell's energy cycle uses ATP, which yields energy and is recycled in its low-energy form, AMP. Accumulation of AMP occurs when energy stores are low, and this signals a reduction in PKA.
The article makes a point that, though the benefits of long-term caloric restriction have been studied extensively, this kind of rejuvenation of the immune system has never been observed with CR alone.
Much of the article is theoretical, connecting decline of the immune system to many of the medical issues associated with aging. Arthritis and even Alzheimer's disease are rooted in auto-immune reactions. The steep rise in cancer with age is believed to be related to the immune system's failure to detect cancer in its early stages and to eliminate pre-cancerous cells. It is to be hoped that rejuvenating the immune system might have broad anti-aging effects.
Why does it work?
Evidence for programmed aging