Aubrey de Grey has rallied the world\u2019s scientific community and its funders to attack the biological basis of aging, which underlies the majority of disease and suffering in the developed world. Since 2003, he has organized bi-annual conferences, bringing together innovative biologists, medical researchers and a few policy wonks to share knowledge and perspectives, to coordinate and support each others\u2019 efforts. Below I report highlights from this year\u2019s meeting, SENS 6, which I attended last week at Queens College, Cambridge.<\/i><\/p>\n
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Caloric Restriction in Monkeys \u2013 Reconciling Two Studies<\/strong><\/p>\n This year and last year, two parallel studies of caloric restriction in rhesus monkeys reported their results. Science reporters framed their conclusions as contradictory. In Madison, the CR monkeys lived longer, while in Baltimore, they did not. Both studies reported robust benefits for many aspects of health in the CR monkeys. What I learned last week was that the Baltimore monkeys had a much leaner diet than the Madison monkeys. In fact, the control monkeys in Baltimore \u2013 those that were supposed to be \u201cfully-fed\u201d \u2013 got about as many calories per day as the CR monkeys in Madison. A natural interpretation of the two results is that modest CR extends life span but that severe CR doesn\u2019t extend life span further (though it may improve health and lower rates of cancer and heart disease). \u00a0Read more<\/a><\/p>\n Another interesting subplot: the Madison diet formula was both high-fat and high-glycemic index, while lower in protein than the Baltimore formula. The Madison diet was completely synthetic (so it could be precisely controlled) including 28% sucrose. The Baltimore diet was based on whole grains and fish meal, with the rationale that there are micronutrients in whole foods that may be important though we have not yet catalogued them. When two groups of mice were fed on these two formulas, adjusted to the same number of calories, the ones on the Madison diet gained weight while those on the Baltimore diet did not. This echoes a theme that is reported in Scientific American this month<\/a>: the body\u2019s caloric budget is not the primary determinant of obesity. The same number of calories from different sources can have dramatically different effects on metabolism. I\u2019ll write more on this next week.<\/p>\n <\/p>\n Exercise vs Caloric Restriction<\/strong><\/p>\n For the last ten yeas, Luigi Fontana of Washington University St Louis has been conducting an ongoing study of two groups of people who exercise fanatically (by middle-class US standards) and who seriously restrict their food intake (same standard). Both groups have dramatically improved biomarkers compared to the average American couch potato. There are some differences between the two. Exercise seems to be better for lowering markers of insulin resistance \u2013 the \u201cmetabolic syndrome\u201d or \u201cType 2 Diabetes\u201d that underlies the diseases of old age. Diet works better to lower cardiovascular risk factors. Both work to lower indicators of cancer risk. \u00a0(It will be many years before there is data to evaluate the effect of CR on human mortality.) \u00a0\u00a0Read more<\/a><\/p>\n <\/p>\n An aging clock in the brain<\/strong><\/p>\n Dongsheng Cai of Einstein Medical Center in New York reported that age-related inflammation is especially prominent in a region of the brain called the hypothalamus, which is known to regulate body rhythms. The hypothalamus is especially sensitive to a signal hormone called NFk<\/span>B<\/a> that has damaging effects over the whole body. In experiments with flies and mice, life span can be extended by blocking the action of NFk<\/span>B. Read more<\/a><\/p>\n <\/p>\n Spermidine<\/strong><\/p>\n Frank Madeo of University of Graz in Austria reported on experiments with a small molecule called spermidine. Fed to yeast cells, it increases life span dramatically, with smaller but still significant effects in flies and worms. Life span of mice can be increased by about 10% with spermidine in the diet. The mechanism seems to be stimulation of the process called autophagy<\/i>, by which each cell cleans up its waste products, digesting them in organelles called lysosomes<\/i>. Spermidine is part of the body\u2019s metabolism, but its concentration declines with age. It is not available as a supplement, to my knowledge. The best dietary source is a Japanese fermented soy product called natto<\/i>, which is famous for its vile flavor. Other dietary sources include soy products and wheat germ. And yes, it is found at high concentrations in semen. \u00a0\u00a0Read more<\/a><\/p>\n <\/p>\n Alternative to Chemotherapy and Radiation<\/strong><\/p>\n Dr M Rigdon Lentz (an American) runs a German clinic with a unique cancer treatment. Cancer cells protect themselves from attack by the body\u2019s immune system by spitting out many \u201cfalse target\u201d molecules that attract killer T cells in the blood and distract them from the real culprit, the cancer cells themselves. Lentz\u2019s procedure involves filtering these decoy molecules from the blood. Often this is sufficient to initiate a fierce immune assault on the tumors, which flare up hot and red. Lentz described some dramatic cures. He reports major regression of tumors in 70% of his patients, despite the fact that most of them have been treated previously with chemo and\/or radiation and traditional oncology has given up on them. \u00a0 \u00a0Read more<\/a><\/p>\n <\/p>\n DRACO \u2013 kills all virus-infected cells<\/strong><\/p>\n Todd Rider of MIT is quietly witty on-stage and charmingly self-effacing, but his program is radically ambitious. He wants to cure all infectious disease.<\/p>\n DRACO is an acronym for D<\/strong>ouble-stranded R<\/strong>NA-A<\/strong>ctivated C<\/strong>aspase O<\/strong>ligomizer. Start with the observation that single strands of RNA are used in all cells, but double-stranded RNA is found only in cells infected by viruses. The DrACO molecule has three parts: One part speaks to the body\u2019s \u201cmail system\u201d that looks at address tags on a molecule, and uses those to send them to a particular cell. DRACO molecules are targeted to a particular kind of cell that is infected. Part two is a detector of double-stranded RNA. And if dsRNA is found, then part three is activated: molecular signals that trigger cell death. The bottom line is that DRACO molecules can find cells that are infected with any virus, distinguish them from uninfected cells, and selectively signal the cell to destroy itself. It\u2019s been tested in test tubes and in mice it cures, for example, the flu. Rider\u2019s lab is producing only tiny quantities of DRACO at present, but by year\u2019s end he hopes to ramp up production for much wider testing. \u00a0\u00a0Read more<\/a><\/p>\n <\/p>\n RTEs = Retro Transposable Elements<\/strong><\/p>\n Half of our DNA consists of repetitious stretches of DNA that never get translated into proteins. This was once referred to as \u201cjunk DNA\u201d or even \u201cparasitic DNA\u201d, but it probably plays an important role in evolution. One piece of evidence for this is that RTEs of recent origin (those unique to primates) are a lot more active and mobile. They\u2019re the part of us that is presently evolving. John Sedivy of Brown University reported that senescent cells \u2013 cells that have depleted their telomeres \u2013 are far more likely to have active RTE\u2019s. These DNA segments make RNA copies of themselves which can then be \u201cretro-transcribed\u201d back into the chromosome, with disruptive consequences. (Transcription = DNA\u2192RNA, part of the path by which chromosomes control the cell; Retro-transcription = RNA\u2192DNA, an unusual and often pathological process) \u00a0 \u00a0Read more<\/a><\/p>\n <\/p>\n Retinoic Acid promotes regeneration of damaged tissue<\/strong><\/p>\n Retinoic Acid is an ingredient in prescription cremes which treat acne and also aging skin. Malcolm Maden from University of Florida reported that retinoic acid promotes regeneration generally. Read more<\/a><\/p>\n <\/p>\n Genetic therapy is much advanced<\/strong><\/p>\n Frank Church of Harvard reported on the state of the art in gene therapy. Fourteen years ago, the first gene transplant experiments resulted in death of a (very sick) teen patient, and set the field back several years. But advances in the interim make it possible now to insert a gene safely into a large number of cells of a lilving body, and target them to a precisely specified position on a chosen chromosome. This is done using\u00a0CRISPR<\/a>s, which are short stretches of RNA with a distinctive palindromic pattern, used by viruses to find the right place to insert themselves into a host genome. <\/p>\n Plasticity of the brain<\/strong><\/p>\n Jean H\u00e9<\/span><\/span><\/span>bert of Einstein Medical Center in New York is working to inject neural stem cells into the brain, to grow new nerves. This might seem like an impossible challenge. Nerve cells regenerate at a rate lower than any other cell type in the body, and even if we got them to regrow, how would they come to carry the knowledge and skills that we have acquired during a lifetime? H\u00e9bert\u00a0reports a hopeful and amazing fact: In patients with brain tumors that destroy function in one part of the brain, another part picks up the function smoothly and without noticeable disruption. This has been noted with fMRI studies based on Boca\u2019s area, which houses language. \u00a0\u00a0Read more<\/a><\/p>\n <\/p>\n Growing a liver on a lymph node<\/strong><\/p>\n There is a long waiting list for liver transplants. In the US, 90% of patients with liver failure will die before they get a transplant. Some have proposed transplanting livers from pigs. Eric Lagasse of Wake Forest Inst for regenerative medicine has another idea. He has had success growing new livers from stem cells in the patient\u2019s body. Liver progenitor cells are implanted in a lymph node, which seems to provide a favorable environment for growth. In mouse models, 70% are able to grow a functional liver “ectopically”, meaning in a part of the body where it does not belong.
\nRead about CRISPR
\nRead about Gene Therapy<\/a><\/a><\/p>\n
\nRead more<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"