{"id":687,"date":"2018-02-06T21:45:53","date_gmt":"2018-02-06T21:45:53","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=687"},"modified":"2018-02-07T13:55:24","modified_gmt":"2018-02-07T13:55:24","slug":"how-to-test-interactions-among-life-extension-treatments","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2018\/02\/06\/how-to-test-interactions-among-life-extension-treatments\/","title":{"rendered":"How to Test Interactions among Life Extension Treatments"},"content":{"rendered":"<p><b>The Most Promising Way Forward for Anti-Aging Science Toda<\/b><span style=\"font-weight: 400\">y<\/span><\/p>\n<p><i><span style=\"font-weight: 400\">We now have many effective interventions <\/span><\/i><span style=\"font-weight: 400\">(<\/span><i><span style=\"font-weight: 400\">mostly of small effect<\/span><\/i><span style=\"font-weight: 400\">)<\/span><i><span style=\"font-weight: 400\"> for longevity and preventive care. \u00a0Most readers of this blog take more than one supplement each day; some of us (I confess) take very many. \u00a0We make an unthinking assumption that \u201cmore is better\u201d, or rather that if A is beneficial and B is beneficial then if we take A and B we can get the benefits of both. \u00a0We don\u2019t think to question or deconstruct this reasoning. \u00a0It is rooted in a reductionism that works pretty well in the physical sciences, much less well in biology. \u00a0<\/span><\/i><\/p>\n<p><i><span style=\"font-weight: 400\">We know that the benefits of all these interventions don\u2019t just add up like numbers in a spreadsheet, but we continue to act as though this were our reality.<\/span><\/i><\/p>\n<p><i><span style=\"font-weight: 400\">The truth is that we know almost nothing about the cross-talk among different health interventions. \u00a0\u00a0The reasons so few experiments have been done are plain enough, but the situation has become untenable. \u00a0There is an urgent need to understand the interactions among treatments. We might begin with those that are individually most promising, but expect surprises. \u00a0The combinations that offer the greatest longevity benefits may turn out to be pieced together from components that individually have little or no effect.<\/span><\/i><\/p>\n<hr \/>\n<p><span style=\"font-weight: 400\">I might have said \u2018the most promising way forward for medical research today, because I believe that anti-aging science is the most productive area of medical research.\u00a0 If you are reading this page, you probably know this already, but we all take comfort in confirmation of what we already know. So: <\/span><\/p>\n<p><span style=\"font-weight: 400\">Prevention is more cost-effective than treatment.\u00a0 The root cause of most disease in the developed world is aging.\u00a0 This point has been made decisively [<a href=\"https:\/\/www.healthaffairs.org\/doi\/abs\/10.1377\/hlthaff.2013.0052\">for example<\/a>], most eloquently <a href=\"https:\/\/books.google.com\/books?id=vlBAKAESSg4C\">by Aubrey de Grey<\/a>.\u00a0 (The root cause of most disease in the third world is poverty, and ending poverty is also an essential imperative, but it is not a subject for medical research.)\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">The problem of interactions has been neglected for a number of reasons: \u00a0<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Unconscious linear thinking<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">The dizzying number of combinations that need to be studied<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">The want of a guiding paradigm that would provide context for individual studies<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Scientific inertia: \u00a0researchers are more likely to study (and funders are more likely to support) research programs that are established and proven<\/span><\/li>\n<\/ul>\n<p><span style=\"font-weight: 400\">But the problem is potentially of great import. \u00a0We expect a great deal of redundancy among the mechanisms of action of various interventions we know about. \u00a0Taking two or three or four drugs that address the same biological pathway is likely to be a costly waste. \u00a0More rarely, longevity drugs may interact in ways that actually interfere and reduce overall effectiveness. \u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">But we have good reason to hope that in rare cases there are combinations that are more than the sum of their parts. \u00a0These fortuitous combinations synergize to offer greater benefits than they provide separately. \u00a0Finding a few such combinations would be a jackpot that justifies many, many expected null results.<\/span><\/p>\n<p><b>The huge number of possibilities to be covered<\/b><\/p>\n<p><span style=\"font-weight: 400\">If we begin with 30 individual interventions, there are 435 pairs of interactions and 4060 combinations of three and 27,405 combinations of four.\u00a0 If we think traditionally, each one of these combinations is a research program in itself, requiring at least several person-years of professional effort plus overhead.\u00a0 This is the daunting reality that confronts anyone who is intent on beginning to address the problem of interactions. \u00a027,405 experiments of any kind is a labor of Hercules, even for a well-funded, fully roboticized biomedical lab.<\/span><\/p>\n<p><span style=\"font-weight: 400\">There is a hierarchy of experimental models for studying anti-aging interventions:<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Human cell cultures are the cheapest and fastest, but we learn the least<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Complementing human cells are yeast cells, which actually have a life expectancy and some biology that overlaps our own<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Studies of thousands of <\/span><i><span style=\"font-weight: 400\">C. elegans <\/span><\/i><span style=\"font-weight: 400\">worms can be done efficiently with robotic controls and\u00a0<a href=\"http:\/\/www.quantworm.org\">worm counters<\/a>.<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Fruitflies are a great deal \u201cmore like us\u201d than worms and they can be raised in large numbers, live just a few weeks.<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Lab rats and mice are expensive, but they are mammals with biology that is much like our own. \u00a0Experiments in rodent longevity last 2 to 3 years.<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Human trials require extensive safety measures and typically take decades to see subtle changes in health and mortality statistics; but this is the most direct indication of what we want to know.<\/span><\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-large\" src=\"https:\/\/www.ebi.ac.uk\/sites\/ebi.ac.uk\/files\/groups\/external_relations\/images\/wide-imagery\/Mouse_Shadow_EMBL-EBI_780x400.jpg\" width=\"4334\" height=\"2222\" \/><\/p>\n<p><b>So, how might we begin?<\/b><\/p>\n<p><span style=\"font-weight: 400\">We have no idea what we will find. \u00a0Maybe there will be a few spectacular combinations. \u00a0Maybe the interactions will turn out to be small, mostly negative, and boringly expected.\u00a0 (My guess is that both of these will turn out to be true.)\u00a0 We should not try to define the second stage of the program until we have results from the first.\u00a0\u00a0<\/span><\/p>\n<p>The first step is to choose the most promising interventions to combine.\u00a0\u00a0<span style=\"font-weight: 400\">A great number of drugs and supplements are known that extend lifespan in rodents and\/or lower mortality in human epidemiology. \u00a0Magalhaes and Kaeberlein have put together a <\/span><a href=\"http:\/\/lifespandb.sageweb.org\/search\/index\/t\/observations\/q\/species%3A%22Mus+musculus%22\"><span style=\"font-weight: 400\">large database of animal studies<\/span><\/a><span style=\"font-weight: 400\"> that seems to be off-line at present.\u00a0 Another version is live at <a href=\"http:\/\/genomics.senescence.info\/drugs\/\" target=\"_blank\" rel=\"noopener\">this address<\/a>.\u00a0 Here is a list I proposed in this column two years ago:<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Rapamycin<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Aspirin<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Metformin<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Melatonin<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Deprenyl<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">ALK5 inhibitors<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Epitalon\/Epithalamin<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">MitoQ\/SkQ<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Beta Lapachone (Pao d\u2019Arco)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Spermidine<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Berberine<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Dinh lang (Policias fruticosum)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Pterostilbene\/Resveratrol<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Gynostemma pentaphyllum (jiao-gu-lan)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">N-Acetyl Cysteine (NAC) \/ Glutathione and precursors<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Ashwagandha<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Turmeric\/curcumin<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">C60<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Oxytocin (not oral)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">J147 (a promising new Alzheimer\u2019s drug)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">NR, NMN and NAD precursors<\/span><\/li>\n<\/ul>\n<p><span style=\"font-weight: 400\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-large\" src=\"http:\/\/www.orbisbio.com\/BlogPics\/47_formulations_pediatric_geriatric.png\" width=\"1000\" height=\"667\" \/>We might add <\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Polyphenols from tea<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Flavinoids from blueberries<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Angiotensin inhibitors<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">NLRP3 antibodies<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Acetyl L-Carnitine<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Piracetam<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">DHEA<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Statin drugs<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Cardarine \/ GW501516 \/ PPAR agonists<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Dasatinib \/ Quercetin<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">FOXO4-DRI<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Astaxanthin<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Momordica charantia (bitter melon)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Gotu kola \/ Bacopa<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Reishi mushroom<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Astragalus extracts<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Pine bark extract<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Ginseng<\/span><\/li>\n<li>Acarbose<\/li>\n<li>BHT<\/li>\n<\/ul>\n<p><span style=\"font-weight: 400\">Interventions not in pill form include <\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Exercise<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Caloric restriction<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Intermittent fasting (various schedules)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Plasma transfusions from younger individuals<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Platelet-rich plasma<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Transplanted young thymus<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Transplanted young suprachiasmatic nucleus<\/span><\/li>\n<\/ul>\n<p><span style=\"font-weight: 400\">How to prioritize and explore the huge number of combinations?\u00a0 Here are four ways we might begin to sort through the possibilities:<\/span><\/p>\n<ol>\n<li><b><i>Use theory: Look for biochemical mechanisms that seem complementary<\/i><\/b><\/li>\n<li><b><i>Traditional Chinese Medicine, Ayurvedic medicine and other ancient traditions suggest combinations of herbs that long experience says function together.<\/i><\/b><\/li>\n<li><b><i>Broad screens for especially potent combinations<\/i><\/b><\/li>\n<li><b><i>Statistical mining of an on-line registry of what people are taking presently<\/i><\/b><\/li>\n<\/ol>\n<p><span style=\"font-weight: 400\">Let\u2019s look at these one at a time.<\/span><\/p>\n<p><strong>1<\/strong>.\u00a0<b>Biochemical Theory<\/b><\/p>\n<p><span style=\"font-weight: 400\">We know a few biochemical pathways that are linked to longevity. \u00a0They all overlap and talk to each other. \u00a0Nevertheless, we expect that treatments that address the same pathway are likely to be redundant, whereas treatments that address distinctive pathways have a better chance of synergizing. \u00a0For example, insulin resistance is a robust hallmark of aging. \u00a0The insulin pathway is most plastic and most accessible to intervention. \u00a0Fasting and caloric restriction address the insulin pathway, as do metformin berberine, jiaogulan and bitter melon. \u00a0Exercise has many benefits, some of which work through the insulin pathway.<\/span><\/p>\n<p><span style=\"font-weight: 400\">We might continue classifying interventions that address other pathways. \u00a0Here are some longevity pathways of which I am aware:<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Insulin<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">mTOR<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Inflammation<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Immune senescence \/ thymic involution<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Epigenetic reprogramming \/ transcription factors<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Mitochondrial senescence<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Autophagy<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Anabolism \/ Catabolism imbalance<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Telomere attrition<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">P53 \/ Apoptosis<\/span><\/li>\n<\/ul>\n<p><span style=\"font-weight: 400\">Someone who knows more biochemistry than I do might be willing to classify the interventions I list (and others) according to these 10 pathways (and others). \u00a0Here is a template in Google Sheets, which I establish as an open Wiki. <\/span><a href=\"http:\/\/tinyurl.com\/longevity-pathways\"><span style=\"font-weight: 400\">http:\/\/tinyurl.com\/longevity-pathways<\/span><\/a><\/p>\n<p><b>2. Eastern and Indigenous Medical Traditions<\/b><\/p>\n<p><span style=\"font-weight: 400\">Many useful modern medicines are derived from ancient folk wisdom. \u00a0But this work has proceeded with a deductive logic, isolating active chemicals from whole plants (as aspirin from willow bark, cycloastragenol from astragalus, and curcumin from turmeric). \u00a0Many folk traditions, especially Traditional Chinese Medicine, are based on not just whole herbs but combinations of herbs that have been found over the ages to work together. \u00a0Ideas may be taken from these traditions to prioritize combinations for testing. \u00a0For example, the best known Chinese <\/span><span style=\"font-weight: 400\">longevity formula is Shou-wu-chi (<\/span><a href=\"https:\/\/en.wiktionary.org\/wiki\/%E9%A6%96\"><span style=\"font-weight: 400\">\u9996<\/span><\/a><a href=\"https:\/\/en.wiktionary.org\/wiki\/%E4%B9%8C\"><span style=\"font-weight: 400\">\u4e4c<\/span><\/a><a href=\"https:\/\/en.wiktionary.org\/wiki\/%E6%B1%81\"><span style=\"font-weight: 400\">\u6c41<\/span><\/a><span style=\"font-weight: 400\">;), which is compounded of (list from <\/span><a href=\"https:\/\/en.wikipedia.org\/wiki\/Shou_Wu_Chih\"><span style=\"font-weight: 400\">Wikipedia<\/span><\/a><span style=\"font-weight: 400\">):<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><a href=\"https:\/\/en.wikipedia.org\/wiki\/Root\"><span style=\"font-weight: 400\">Root<\/span><\/a><span style=\"font-weight: 400\"> of <\/span><a href=\"https:\/\/en.wikipedia.org\/wiki\/Polygonum_multiflorum\"><i><span style=\"font-weight: 400\">Polygonum multiflorum<\/span><\/i><\/a><span style=\"font-weight: 400\"> (Radix Polygoni multiflori, also called <\/span><i><span style=\"font-weight: 400\">fo-ti<\/span><\/i><span style=\"font-weight: 400\"> or <\/span><i><span style=\"font-weight: 400\">ho shou wu<\/span><\/i><span style=\"font-weight: 400\">) &#8211; 25%<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Root of <\/span><a href=\"https:\/\/en.wikipedia.org\/wiki\/Angelica_sinensis\"><i><span style=\"font-weight: 400\">Angelica sinensis<\/span><\/i><\/a><span style=\"font-weight: 400\"> (Chinese angelica, also called <\/span><i><span style=\"font-weight: 400\">dong quai<\/span><\/i><span style=\"font-weight: 400\"> or <\/span><i><span style=\"font-weight: 400\">danggui<\/span><\/i><span style=\"font-weight: 400\">) &#8211; 25%<\/span><\/li>\n<li style=\"font-weight: 400\"><a href=\"https:\/\/en.wikipedia.org\/wiki\/Rhizome\"><span style=\"font-weight: 400\">Rhizome<\/span><\/a><span style=\"font-weight: 400\"> of <\/span><a href=\"https:\/\/en.wikipedia.org\/wiki\/Polygonatum\"><i><span style=\"font-weight: 400\">Polygonatum<\/span><\/i><\/a><i><span style=\"font-weight: 400\"> sibiricum<\/span><\/i><span style=\"font-weight: 400\"> (Solomon&#8217;s Seal) &#8211; 20%<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Rhizome of <\/span><a href=\"https:\/\/en.wikipedia.org\/wiki\/Rehmannia\"><i><span style=\"font-weight: 400\">Rehmannia<\/span><\/i><\/a><i><span style=\"font-weight: 400\"> glutinosa<\/span><\/i><span style=\"font-weight: 400\"> &#8211; 10%<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Rhizome of <\/span><a href=\"https:\/\/en.wikipedia.org\/wiki\/Ligusticum\"><i><span style=\"font-weight: 400\">Ligusticum<\/span><\/i><\/a><i><span style=\"font-weight: 400\"> wallichii<\/span><\/i><span style=\"font-weight: 400\"> (Chinese lovage, also called <\/span><i><span style=\"font-weight: 400\">Ligusticum chuanxiong<\/span><\/i><span style=\"font-weight: 400\">) &#8211; 10%<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Root of <\/span><a href=\"https:\/\/en.wikipedia.org\/wiki\/Angelica_dahurica\"><i><span style=\"font-weight: 400\">Angelica dahurica<\/span><\/i><\/a><span style=\"font-weight: 400\"> (Dahurian Angelica, also called <\/span><i><span style=\"font-weight: 400\">Angelica glabra<\/span><\/i><span style=\"font-weight: 400\"> Makino) &#8211; 7%<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Fruit of <\/span><a href=\"https:\/\/en.wikipedia.org\/wiki\/Amomum\"><i><span style=\"font-weight: 400\">Amomum<\/span><\/i><\/a><i><span style=\"font-weight: 400\"> villosum<\/span><\/i><span style=\"font-weight: 400\"> (Villous Amomum, a type of <\/span><a href=\"https:\/\/en.wikipedia.org\/wiki\/Cardamom\"><span style=\"font-weight: 400\">cardamom<\/span><\/a><span style=\"font-weight: 400\">) &#8211; 2%<\/span><\/li>\n<li style=\"font-weight: 400\"><a href=\"https:\/\/en.wikipedia.org\/wiki\/Clove\"><span style=\"font-weight: 400\">Clove<\/span><\/a><span style=\"font-weight: 400\"> &#8211; 1%<\/span><\/li>\n<\/ul>\n<p>Other ingredients<span style=\"font-weight: 400\"> may also include:\u00a0<\/span><a href=\"https:\/\/en.wikipedia.org\/wiki\/Hedychium_coronarium\"><i>Hedychium coronarium<\/i><\/a> (white ginger),\u00a0<i>Jambosa caryophy<\/i> Llus Ndz,\u00a0<a href=\"https:\/\/en.wikipedia.org\/wiki\/Citron\">Citron<\/a> (<i>Citrus medica<\/i>), and\u00a0<a href=\"https:\/\/en.wikipedia.org\/w\/index.php?title=Conioselinum_univittatum&amp;action=edit&amp;redlink=1\"><i>Conioselinum univittatum<\/i><\/a> Turcz<\/p>\n<p><span style=\"font-weight: 400\">The Ayurvedic tradition is less contains fewer formulas, but combinations that are said to contribute to longevity include these (which I found, just for illustration, at\u00a0<\/span><a href=\"https:\/\/www.banyanbotanicals.com\/info\/blog-the-banyan-insight\/details\/top-7-ayurvedic-herbs-for-rejuvenation\"><span style=\"font-weight: 400\">Banyan Botanicals<\/span><\/a><span style=\"font-weight: 400\">)<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Haritaki (Terminalia chebula)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Guduchi (Tinospora cordifolia)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Amalaki (Embelica officinalis)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Kumari (Aloe barbadensis, or aloe vera)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Guggulu (Commiphora mukul)<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Brahmi or gotu Kola (Centella asiatia) or closely-related Bacopa<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Ashwagandha (Withania somnifera)<\/span><\/li>\n<\/ul>\n<p><b>3. Broad screens for particularly effective combinations<\/b><\/p>\n<p><span style=\"font-weight: 400\"><a href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2015\/12\/22\/we-know-nothing-about-longevity-drug-interactions\/\">Two years ago in this space<\/a>, I proposed a screening protocol in which all combinations of 3 interventions from a universe of 15 would be tried on just 3 mice each. \u00a0I showed with a <\/span><a href=\"https:\/\/www.researchgate.net\/publication\/321798751_Combining_life_extension_treatments_A_proposal_for_high-throughput_testing_in_rodents?_iepl%5BviewId%5D=bI9FTYpnvSTQ8W06URbuWn2C&amp;_iepl%5BprofilePublicationItemVariant%5D=default&amp;_iepl%5Bcontexts%5D%5B0%5D=prfpi&amp;_iepl%5BtargetEntityId%5D=PB%3A321798751&amp;_iepl%5BinteractionType%5D=publicationTitle\"><span style=\"font-weight: 400\">computational model<\/span><\/a><span style=\"font-weight: 400\"> that if these included at least one lucky combination that increased longevity by more than 50%, then, despite the small number of mice, it would be identified with at least 80% confidence. \u00a0Combinations of three from a universe of fifteen is a kind of sweet spot for this particular experimental design, and much less is learned if the numbers are scaled back.\u00a0 This means it is not feasible to test the concept on a small scale.\u00a0 The full proposal requires 1365 mice in cages of three, followed for at least two years. \u00a0Cost estimate is about $2 million in the US or Europe, perhaps as low as $500,000 to do the same experiment in China. \u00a0I would be eager to work with any lab that has the expertise and the facilities to implement this protocol. \u00a0The experimental design and simulated analysis was recently published in English in a <\/span><a href=\"https:\/\/link.springer.com\/article\/10.1134\/S0006297917120057\"><span style=\"font-weight: 400\">Russian journal<\/span><\/a><span style=\"font-weight: 400\">.<\/span><\/p>\n<p><b><strong>4<\/strong>. Data-mining of an online registry where people record what supplements they are taking and commit to reporting their health history<\/b><\/p>\n<p><span style=\"font-weight: 400\">It would be a great public service if someone were to establish a web-based registry where individuals could share information about what supplements they are taking and what results they are getting. \u00a0Over years, this could turn into a data miner\u2019s heaven for information about individual drugs and lifestyles and their interactions. \u00a0The subject is too big for a controlled experiment, but enlisting the public would be a great and greatly-rewarding project.<\/span><\/p>\n<p><span style=\"font-weight: 400\">I know there are web sites such as <\/span><a href=\"http:\/\/www.longecity.org\/forum\/\"><span style=\"font-weight: 400\">Longecity<\/span><\/a><span style=\"font-weight: 400\"> that are excellent resources for anecdotal accounts of others\u2019 experiences. \u00a0But the data is not in a format that lends to statistical summaries. \u00a0If you know of an existing online database of this sort, please reach out and share the web address with me. \u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">I have preliminary plans to create such a web site in conjunction with a forthcoming book project.<\/span><\/p>\n<p><b>The Challenge<\/b><\/p>\n<p>There may already be a viable plan for major life extension hiding in plain sight.\u00a0 <span style=\"font-weight: 400\">There is no extant research program to explore the relationships and interactions among life extension measures. \u00a0<\/span>Eventually, some large, well-funded agency (perhaps NEA or the Buck Institute) will take on this project in a systematic way.\u00a0 But the large organizations are conservative, and are unlikely to begin until the ice is broken.\u00a0 Thus,\u00a0<span style=\"font-weight: 400\">even the first shards of information in this area are likely to be valuable indications of a new research direction.<\/span><\/p>\n<p><span style=\"font-weight: 400\">If you have a research lab, or if you know are connected to someone who might be interested in this project, or if you have a funding source, please let us work together.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The Most Promising Way Forward for Anti-Aging Science Today We now have many effective interventions (mostly of small effect) for longevity and preventive care. \u00a0Most readers of this blog take more than one supplement each day; some of us (I confess) take very many. \u00a0We make an unthinking assumption that \u201cmore is better\u201d, or rather &#8230; <a title=\"How to Test Interactions among Life Extension Treatments\" class=\"read-more\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2018\/02\/06\/how-to-test-interactions-among-life-extension-treatments\/\" aria-label=\"Read more about How to Test Interactions among Life Extension Treatments\">Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":688,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-687","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.4 (Yoast SEO v27.4) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>How to Test Interactions among Life Extension Treatments - Josh Mitteldorf<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2018\/02\/06\/how-to-test-interactions-among-life-extension-treatments\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How to Test Interactions among Life Extension Treatments\" \/>\n<meta property=\"og:description\" content=\"The Most Promising Way Forward for Anti-Aging Science Today We now have many effective interventions (mostly of small effect) for longevity and preventive care. \u00a0Most readers of this blog take more than one supplement each day; some of us (I confess) take very many. \u00a0We make an unthinking assumption that \u201cmore is better\u201d, or rather ... 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. This makes the mechanism challenging to understand and to model. more at http:\\\/\\\/mathforum.org\\\/~josh\",\"sameAs\":[\"http:\\\/\\\/AgingAdvice.org\"],\"url\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/author\\\/joshmitteldorf\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO Premium plugin. -->","yoast_head_json":{"title":"How to Test Interactions among Life Extension Treatments - Josh Mitteldorf","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/scienceblog.com\/joshmitteldorf\/2018\/02\/06\/how-to-test-interactions-among-life-extension-treatments\/","og_locale":"en_US","og_type":"article","og_title":"How to Test Interactions among Life Extension Treatments","og_description":"The Most Promising Way Forward for Anti-Aging Science Today We now have many effective interventions (mostly of small effect) for longevity and preventive care. \u00a0Most readers of this blog take more than one supplement each day; some of us (I confess) take very many. \u00a0We make an unthinking assumption that \u201cmore is better\u201d, or rather ... 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. 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