{"id":153,"date":"2013-10-08T01:14:27","date_gmt":"2013-10-08T01:14:27","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=153"},"modified":"2013-10-10T00:35:34","modified_gmt":"2013-10-10T00:35:34","slug":"combining-biochemical-pathways-to-longevity-toward-a-recipe-for-the-youth-pill","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/10\/08\/combining-biochemical-pathways-to-longevity-toward-a-recipe-for-the-youth-pill\/","title":{"rendered":"Combining Biochemical Pathways to Longevity: Toward a Recipe for the Youth Pill"},"content":{"rendered":"

From studies in rodents, we now know dozens of treatments that extend life span modestly. \u00a0If we could combine their effects all together, we would have a basis for dramatic life extension! \u00a0But some of these have biochemical actions that overlap, while others are likely to be independent, and \u2013 if we are lucky \u2013 some will be synergistic, so that the combined benefit might be greater than the sum of the treatments individually. \u00a0Experiments with combinations of longevity drugs are the next big thing in anti-aging research.<\/em><\/p>\n

\u00a0\"Deprenyl-mouse-study-summary\"<\/a><\/p>\n

Deprenyl<\/a> is an antidepressant and Parkinson\u2019s treatment (sold as Selegeline, Emsam and Eldepryl). \u00a0Dinh lang is the Vietnamese name for an Asian plant (Policias fruticosum, not available<\/a> to my knowledge in the US), \u00a0root of which is a traditional medicine. \u00a0In 1990, T T Yen and Joseph Knoll worked together on a study of life extension in mice. \u00a0Mice treated with deprenyl lived 22% longer; with the dinh lang, there was 28% life extension; and with the two together, an impressive 35% life extension.<\/p>\n

Interpretation<\/strong>: \u00a0Life extension from the two together is greater than each of the two treatments separately, but not as large as the sum of the two effects. \u00a0Whatever dinh lang and deprenyl do for the mouse\u2019s physiology, there is some overlap in their effects, and some independendent action as well.<\/p>\n

This twenty-year-old longevity study is the only one I\u2019ve seen in which two treatments are combined to determine how the treatments work in tandem. \u00a0A lot more of this kind of work could be done. \u00a0Granted, mouse studies are expensive (in the neighborhood of a million dollars for a mouse lifetime, including controls). \u00a0But these studies of combined treatments will provide a vital bridge between theory and practical life extension in humans.<\/p>\n

We now have evidence for life extension in mammals from many different treatments. \u00a0If we could add these effects together, we would have some stunning results! \u00a0But it is likely that some of them do essentially the same thing, acting through the same biochemical pathways with different agents. \u00a0Only some of the treatments are independent.<\/p>\n

What we know about aging suggests that several independent processes are involved; so Practical life extension for humans will involve a combination of different measures.\u00a0Experiments with combined treatments have the potential to tell us how these pathways may be interrelated, as well as providing practical guidelines for formulating the coming Youth Pill<\/a>.<\/p>\n

The best-known path to life extension works via calorie deprivation or hunger, or simulated hunger. \u00a0Calorie Restriction<\/a> is a probable confounder in many lab studies of life span. \u00a0Last year, Stephen Spindler reviewed<\/a> the literature on life extension studies in rodents, and found that many researchers had not made a clean separation between CR and the particular intervention they were studying. \u00a0The problem is that eating less has a strong and reliable benefit for life span, so any drug or herb that tends to suppress appetite may show a positive benefit for life span \u2013 a real but secondary effect. \u00a0Spindler complains that of the researchers doing life extension studies on mice and rats, very few of them report weight or food consumption, so it is impossible to know if the treatment they are studying has an independent benefit, or if it just induces the animals to eat less.<\/p>\n

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Spindler and Anisimov<\/strong><\/p>\n

The (UC Riverside) laboratory of Stephen Spindler<\/a> has conducted mouse studies of longevity, reporting largely negative results. \u00a0But when Spindler assembled the review (cited above<\/a>), his criterion was to include every substance that has been reported in a peer-reviewed publication to induce life extension in rodents. \u00a0These studies come from differently labs, and the quality is uneven. \u00a0Some are corroborated by more than one study from more than one lab, some have never been replicated, and some have been the subject of negative findings in Spindler\u2019s own lab, but he lists them anyway. \u00a0Across the ocean, the Russian researcher who is Spindler\u2019s opposite number is Vladimir Anisimov<\/a> of the Petrov Institute<\/a> in St Petersburg. \u00a0For decades, Anisimov has operated the largest laboratory in Russia devoted to aging medicine, and has reported many positive results, some of which have been replicated elsewhere. \u00a0Least known of Anisimov\u2019s findings are the very promising results he has reported with short peptide chains<\/a>.<\/p>\n

I think of Spindler and Anisimov as bookends of the anti-aging literature. \u00a0Spindler\u2019s criteria for inclusion are the strictest, and Anisimov\u2019s the most liberal.<\/p>\n

 <\/p>\n

Categorizing the anti-aging molecules<\/strong><\/p>\n

Dozens of treatments that are reported to extend life span in rodents individually have never been tried in combination, and there are hundreds of potential combinations. \u00a0In order to make an educated guess as to which combinations are likely to work better together, it is helpful to categorize their modes of action, as far as they are known. \u00a0To this end, I have listed Spindler\u2019s catalog, plus a few more, in nine groups according to their biochemical pathways. \u00a0There is considerable overlap in the mechanisms of action, so my criteria are somewhat subjective. \u00a0And I don\u2019t claim that this list is exhaustive \u2013 it is Spindler\u2019s list, supplemented by other interventions that I happen to know about. \u00a0Here are the nine groups, with treatments in each category listed in parentheses underneath:<\/p>\n