Short Takes from the 2013 AGE meeting, Baltimore June 1-3
Several talks involved growth hormone one way or another. Growth hormone is hyped as an anti-aging remedy by many supplement sources, but its benefits are likely to be short-term, and there is substantial risk that it actually increases mortality risk in the long run. Holly Brown-Borg made this point quite explicitly. Her research is centered on two strains of mice, a dwarf strain which has a genetic defect for growth hormone, and lives 50% longer, the other is genetically engineered to have extra growth hormone, and it lives 50% shorter than ordinary lab mice. The dwarf mice are super-healthy and don’t get cancer, but you can make them sick by giving them growth hormone.
Valter Longo reported on his research with the little people of Ecuador. Their distinctive genetic endowment is called GHRD for “growth hormone receptor deficiency”. They never get cancer, and have lower rates of cognitive decline with age. Many of them love to eat and drink, and despite their habitual Bachanalia, maintain their insulin sensitivity with age and don’t get diabetes. Many people enjoy the effects of HGH in the short run, and like what it does to their body image, but it’s likely to be pro-aging in the long run.
Greg Fahy is knowledgeable, innovative, courageous, and looks 15 years younger than his chronological age, and is my friend as well as colleague in this field. He suggested that a short course (<1 year) of HGH might be used to regrow the thymus, and is seeking funds for a pilot experiment with ten subjects, age 50-65. The thymus is a small organ behind the breastbone that trains our white blood cells to distinguish “self” from “invader”, and which shrinks steadily over our lifetimes. “Thymic involution” is closely associated with aging of the immune system. If Greg is able to follow through, I’ll let you know how this works out.
Blueberry Man comes to these meetings, and cites dozens of studies for diverse health benefits from eating blueberries. He talks about being on crutches with degeneration of his joints a few years ago, from which he recovered completely after starting to eat two cups of blueberries a day.
The research of Eric Smith is centered on glutathione, and its precursor, a gene called nrf2. Glutathione is an anti-oxidant working throughout every cell, detoxifying especially the liver. We need glutathione more as we get older, but our bodies make less of it. Centenarians and people on calorie restriction both have more glutathione than the rest of us. In genetically modified animals, glutathione is associated with longevity. I have been down on dietary anti-oxidants in the past, but I believe that up-regulating our own glutathione is a good thing for longevity. Unfortunately, we can’t take a glutathione pill. It doesn’t make it through the digestive system, and it doesn’t last in the body, as it is continually being used and recycled. There is a supplement called NAC (n-acetyl cysteine) which is a biochemical precursor, and some people take it to try to induce the body to make more glutathione. SAMe has also been demonstrated to increase glutathione levels. Nrf2 is a gene important to the synthesis of glutathione, and there is a commercial mixture of herbs calledProtandim that purports to stimulate the body’s production of nrf2. Interesting to me is that the first ingredient in Protandim is also the first ingredient in Product B, which I take as a telomere activator. That is silymarin, or milk thistle.
This is a prescription drug that slows the body’s uptake of sugar, so blood sugar doesn’t spike after a high-carb meal and then plummet back down afterward. I believe these cycles are related to the loss of insulin sensitivity that is a common characteristic of human aging, leading to diabetes and higher risk of all the diseases of old age. I have heard of many treatments to promote insulin sensitivity, and promise to do some reading and write a post about these herbs and drugs soon. In the meantime, there’s background in my article on metformin.
In 2009 came a sensational report from David Harrison’s group at Jackson National Labs. Mice received a short course of rapamycin late in life, and still showed a 15% life extension (measured from birth). Researchers have been excited about its anti-aging potential, and in three short years, there have been 10 more studies documenting life extension up to about 25% in various strains of mice. There were several major presentations at the conference focused on rapamycin. Rapamycin binds to two sites, called TORC1 and TORC2 (TOR stands for “target of rapamycin”). Joe Bauer reported his theory that TORC2 holds most of the benefits, and TORC1 most of the dangers of rapamycin, and he is working to separate the two effects. Arlan Richardson offered an hour-long advertisement for rapamycin as a cancer treatment, for cardiac health and prevention of cognitive decline. He reluctantly admitted that it also causes cataracts, slows healing, and contributes to Type 2 diabetes. Conference consensus (including this author) is that rapamycin is an exciting new vehicle for studying aging, but as a general tonic, it’s not ready for prime time.
There have been two ongoing studies of caloric restriction in rhesus monkeys, at University of Wisconsin (UW) and at National Institute of Aging (NIA). Last year and the year before, these two groups came out with their preliminary conclusions from the 25-year project. Newspapers picked up the UW results, and reported: CR Study in Primates Shows Positive Results! The next year, the NIA report was summarized: CR Study in Primates Shows Negative Results! At this meeting, Julie Mattison of NIA and Roz Anderson of UW charmed us with a well-coordinated presentation seeking to clarify the differences between the two studies. Both studies found that the CR animals were healthier, suffered less disease, were more active and looked better than the control animals. (Interesting that Sai Krupa Das summarized the CALERIE study <of CR in humans with almost the identical words.) Both studies found no difference in overall schedule of deaths in the two groups. But when they separated aging-related deaths from accidental deaths, the UW group reported that there was a big difference, with CR animals living far longer on average. Meanwhile, the NIA group reported that there was little difference between the life spans of the two groups. Some of the difference is due to the fact that the UW diet was heavier in sugar, and monkeys assigned to the control group got to eat as much as they wanted. Meanwhile, the NIA group fed both groups of monkeys more protein, less fat, and complex carbs instead of sugar. They also limited the food intake of the control monkeys (though, of course, they ate more than the CR monkeys). It’s still not clear that these are the crucial differences between the two results, and since the total number of monkeys was so small, it is conceivable that the difference was only a statistical fluke.
Fasting before Surgery or Chemotherapy
Calorie restriction not only increases life span but dramatically improves resistance to many kinds of stress. Valter Longo had the idea that it might help the body to withstand the shock of chemotherapy. What he found was promising beyond his expectations, but resistance among doctors and patients has been frustrating to say the least.
I’ve known Valter Longo for 10 years, since he had to work like heck to convince the biology community that yeast cells commit suicide, for altruistic reasons. In the 1990s, he proved that yeast colonies, when starved, partake of a remarkable adaptation in which 95% of them commit suicide, digesting their cytoplasm into food for the other 5%. Most curious is the fact that these animals are genetically homogeneous. How do 5% of them choose themselves as survivors? How could such an adaptation evolve, when there’s so much motivation to “cheat” and bias the odds to be among the 5% beneficiaries rather than the 95% martyrs?
Longo has worked the last several years to establish that fasting before chemotherapy (and radiotherapy) doubly pre-conditions the body. Cancer cells become more sensitive to the chemo, and are killed with more certainty. Meanwhile, the rest of the patient’s cells become less sensitive to chemo, and they survive the insult much better. Patients who fast before chemo report that their nausea and fatigue are greatly reduced. At first, Longo found it was a tough sell to get patientswho are willing to try fasting for two to three days before chemo. Even tougher was the opposition from oncologists, who not only advised against the procedure, but (in the worst cases) found that their patients’ blood sugar was “too low”, and put them on intravenous sugar before chemo! But in the last three years, his idea has taken off, and there are now many, many chemotherapy patients in which the technique has been successful.
James Mitchell of Harvard reported on parallel work with mice, demonstrating that pre-conditioning with fasting protects mice against surgical trauma, dramatically reducing risk of death and improving recovery time. He also experimented with reducing protein only, making up the difference with carbohydrates, and was able to get much of the same protection. Combining calorie restriction and protein restriction worked better than either separately. Mitchell recommends fasting, or perhaps juice fasts before surgery of any kind, except if the patient is frail or emaciated to begin with.
The title of his paper was “Calorie restriction and essenial amino acid restriction contribute additively to the benefits of short-term dietary restriction in mice.” Previously, there had been a lot of speculation whether the mechanism by which calorie restriction worked was really just that the animal was starved of protein, and the mechanism by which protein restriction worked was that the animal was just starved of one essential amino acid (usually methionine). This was the first demonstration I have seen that the effects can be separated, and the benefits ofboth calorie restriction plus methionine restriction are greater than the benefit of either restriction separately
I’ve been attending these meetings for several years, and I continue to find that the meetings are small, there are almost no MDs, and the research seems to occupy a backwater between bench science and medical research. Compared to cancer research or heart or lung disease, the field is way underfunded. Still, research in anti-aging medicine is growing, as policy-makers realize it is a way to address many diseases of old age with a powerful new paradigm.
This post orginally appeared on Josh’s blog here: http://joshmitteldorf.scienceblog.com/2013/06/03/short-takes-from-the-2013-age-meeting-baltimore-june-1-3/
For basic information about healthy living for a long life,
see the author’s permanent page at AgingAdvice.org.