{"id":379,"date":"2015-05-24T21:45:26","date_gmt":"2015-05-24T21:45:26","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=379"},"modified":"2015-05-24T21:45:26","modified_gmt":"2015-05-24T21:45:26","slug":"gdf11-not-so-fast","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2015\/05\/24\/gdf11-not-so-fast\/","title":{"rendered":"GDF11\u2014Not So Fast"},"content":{"rendered":"<p>A research report from Novartis may temper our excitement about GDF11, which was a runner-up for Science Magazine&#8217;s 2014\u00a0<a href=\"http:\/\/www.sciencemag.org\/content\/346\/6216\/1444.full\">Breakthrough Of the Year<\/a>.<\/p>\n<p><b>Bakground<\/b><\/p>\n<p>\u201cHeterochronic parabiosis\u201d is the sanitized word for sewing together as Siamese twins two animals of the same species but different ages. \u00a0Modern implementation as a research technique was pioneered by Clive McCay in the 1950s, the same McCay who brought us caloric restriction in the 1930s.<\/p>\n<p>The two animals share a common pool fo blood. \u00a0What is clear is that the older animal in the pair benefits from young blood. \u00a0Healing is improved, and some tissues are rejuvenated. \u00a0What is less clear: \u00a0what are the elements in the blood that are responsible for the rejuvenation? \u00a0Is there a \u201cyouth serum\u201d, transferred from the young animal to the old; or in fact is there a blood factor responsible for deterioration, and the old animal is benefiting from dilution of his elder toxins? \u00a0Are there a few such blood factors, or too many to form the basis of a practical therapy?<\/p>\n<p>In the last ten years, there has been a diaspora of researchers from the Stanford lab of Tom Rando, young researchers now at Berkeley and Harvard who are pursuing advanced techniques of blood transfer, seeking to isolate the active ingredients. \u00a0A consensus is emerging that<\/p>\n<ul>\n<li>It is not the red or white blood cells, but dissolved proteins in the blood that make the difference.<\/li>\n<li>There are both pro-aging and anti-aging factors in the blood.<\/li>\n<\/ul>\n<p>The big questions remaining:<\/p>\n<ul>\n<li>There are at least several factors of each kind, pro- and anti-aging. \u00a0Is the number of essential blood factors small and manageable, so we might hope to make a \u201cbloody Mary\u201d cocktail? \u00a0Or is the number so large this is impractical?<\/li>\n<li>Will these blood factors reboot the body\u2019s epigenetics so the old body starts producing the young mix itself? \u00a0How long must the body be exposed to the young mix before it starts to produce the young mix itself?<\/li>\n<\/ul>\n<p>Last year in particular saw eye-popping results from the Berkeley lab of Irina and Mike Conboy, and from the Harvard lab of Amy Wagers. \u00a0The Conboys claimed that oxytocin is a blood factor promoting longevity. \u00a0[<a href=\"http:\/\/www.nature.com\/ncomms\/2014\/140610\/ncomms5082\/full\/ncomms5082.html\">ref<\/a>, <a href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/08\/09\/love-death-and-oxytocin\/\">my blog<\/a>] \u00a0Wagers identified GDF11 as a blood factor that declines with age, and enhances strength and endurance when administered to muscle tissue in mice. \u00a0[<a href=\"http:\/\/www.researchgate.net\/profile\/Young_Jang5\/publication\/262074997_Restoring_Systemic_GDF11_Levels_Reverses_Age-Related_Dysfunction_in_Mouse_Skeletal_Muscle\/links\/5424769e0cf238c6ea6ecb75.pdf\">ref<\/a>, <a href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/05\/05\/gdf11-a-hormonal-candidate-for-rejuvenation\/\">my blog<\/a>] \u00a0In humans, GDF11 has been shown to <a href=\"http:\/\/www.trasci.com\/article\/S1473-0502(15)00073-7\/abstract?cc=y=\">increase nerve growth<\/a>.<\/p>\n<p>&nbsp;<\/p>\n<p><b>Cousins of GDF11<\/b><\/p>\n<p>A rejuvenating role for GDF11 was a surprise because it is in the TGF\u03b2 class of hormones, which generally have negative effects on muscles. \u00a0In a <a href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/11\/12\/molecules-in-the-blood-that-signal-self-destruction\/\">2013 blog<\/a>, I identified TGF\u03b2 as one of the blood factors that we have too much of as we age. \u00a0Myostatin is the best-known member of this group, and it inhibits muscle growth. \u00a0Mice lacking the myostatin gene grow double-size muscles and have better insulin sensitivity. \u00a0<a href=\"http:\/\/www.sciencedirect.com\/science\/article\/pii\/S0303720709006388\">Creatine<\/a> is a myostatin inhibitor that is popular among muscle-builders.<\/p>\n<p>Genes for GDF11 and for myostatin are <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3011861\/\">90% identical<\/a>. \u00a0But mice lacking GDF11 don\u2019t have bigger muscles, and in fact they die soon after birth. \u00a0So it\u2019s possible that GDF11 is good and myostatin is bad.<\/p>\n<p>&nbsp;<\/p>\n<p><b>The latest news<\/b><\/p>\n<p>Last week, David Glass and a team at Novartis report that they have failed to reproduce Wagers\u2019s results about GDF11. \u00a0From a <a href=\"http:\/\/www.nature.com\/news\/young-blood-anti-ageing-mechanism-called-into-question-1.17583#\/b4\">Nature News report by Sara Reardon<\/a>:<\/p>\n<blockquote><p>Glass and his colleagues set out to determine why GDF11 had this apparent effect. \u00a0First, they tested the <a href=\"http:\/\/www.nature.com\/news\/reproducibility-crisis-blame-it-on-the-antibodies-1.17586\">antibodies<\/a> and other reagents that Wagers\u2019 group had used to measure GDF11 levels, and found that these chemicals could not distinguish between myostatin and GDF11. When the Novartis team used a more specific reagent to measure GDF11 levels in the blood of both rats and humans, they found that GDF11 levels actually increased with age \u2014 just as levels of myostatin do. That contradicts what Wagers\u2019 group had found.<\/p>\n<p>Glass&#8217;s team next used a combination of chemicals to injure a mouse\u2019s skeletal muscles, and then regularly injected the animal with three times as much GDF11 as Wagers and her team had used. Rather than regenerating the muscle, Glass found, GDF11 seemed to make the damage worse by inhibiting the muscles\u2019 ability to repair themselves. He and his colleagues report their results on <a href=\"http:\/\/www.sciencedirect.com\/science\/article\/pii\/S1550413115002223\">19 May in Cell Metabolism<\/a>.<\/p><\/blockquote>\n<p>Woops. \u00a0The Wagers results may prove to be an error, or it may be that the story is more nuanced. \u00a0It would not be surprising if there is such a thing as too little GDF11 and too much GDF11.<\/p>\n<blockquote><p>Wagers, however, stands by her findings. She says that although at first glance the Novartis group&#8217;s data seem to conflict with her team\u2019s results, there could be multiple forms of GDF11 and that perhaps only one decreases with age. Both papers suggest that having either too much or too little GDF11 could be harmful, she says. She adds that the Novartis group injured the muscle more extensively and then treated it with more GDF11 than her group had done, so the results may not be directly comparable.<\/p>\n<p>&nbsp;\u201cWe look forward to addressing the differences in the studies with additional data very soon,\u201d Wagers says.<\/p>\n<p>Rando expects that researchers will now investigate the finding2 that GDF11 affects the growth of neurons and blood vessels in the brain. \u201cI&#8217;m not sure which result is going to stand the test of time,\u201d he says.<\/p><\/blockquote>\n<p><b>Two Unrelated Items of Interest<\/b><\/p>\n<p>Life Extension magazine for June claims that fear of Testosterone has been unwarranted, that the benefits of T for strength and heart health do not come at a cost in increased cancer risk or decreased longevity. \u00a0(June edition is not yet on-line at LEF, but has been uploaded to Dropbox by a colleague <a href=\"https:\/\/www.dropbox.com\/s\/mtti52k8krvl0ep\/LEF%202015-06.pdf?dl=0\">here<\/a>.)<\/p>\n<blockquote><p>Low endogenous bioavailable testosterone levels have been shown to be associated with higher rates of all cause and cardiovascular-related mortality\u2026<\/p>\n<p>Testosterone replacement therapy has also been shown to improve the homeostatic model of insulin resistance and hemoglobin A1c in diabetics and to lower the BMI in obese patients. These findings suggest that men with lower levels of endogenous testosterone may be at a higher risk of developing atherosclerosis.<\/p>\n<\/blockquote>\n<hr \/>\n<p><a href=\"http:\/\/news.yale.edu\/2015\/05\/21\/research-news-yale-researchers-find-human-specific-gene-turns-back-cellular-clock\">Here<\/a> is an intriguing news release from Yale about a protein found only in primates that is useful for making ordinary cells into stem cells.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A research report from Novartis may temper our excitement about GDF11, which was a runner-up for Science Magazine&#8217;s 2014\u00a0Breakthrough Of the Year. Bakground \u201cHeterochronic parabiosis\u201d is the sanitized word for sewing together as Siamese twins two animals of the same species but different ages. \u00a0Modern implementation as a research technique was pioneered by Clive McCay &#8230; <a title=\"GDF11\u2014Not So Fast\" class=\"read-more\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2015\/05\/24\/gdf11-not-so-fast\/\" aria-label=\"Read more about GDF11\u2014Not So Fast\">Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":0,"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-379","post","type-post","status-publish","format-standard","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>GDF11\u2014Not So Fast - 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\/2015\/05\/24\/gdf11-not-so-fast\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"GDF11\u2014Not So Fast\" \/>\n<meta property=\"og:description\" content=\"A research report from Novartis may temper our excitement about GDF11, which was a runner-up for Science Magazine&#8217;s 2014\u00a0Breakthrough Of the Year. Bakground \u201cHeterochronic parabiosis\u201d is the sanitized word for sewing together as Siamese twins two animals of the same species but different ages. \u00a0Modern implementation as a research technique was pioneered by Clive McCay ... Read more\" \/>\n<meta property=\"og:url\" content=\"https:\/\/scienceblog.com\/joshmitteldorf\/2015\/05\/24\/gdf11-not-so-fast\/\" \/>\n<meta property=\"og:site_name\" content=\"Josh Mitteldorf\" \/>\n<meta property=\"article:published_time\" content=\"2015-05-24T21:45:26+00:00\" \/>\n<meta name=\"author\" content=\"Josh Mitteldorf\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Josh Mitteldorf\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2015\\\/05\\\/24\\\/gdf11-not-so-fast\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2015\\\/05\\\/24\\\/gdf11-not-so-fast\\\/\"},\"author\":{\"name\":\"Josh Mitteldorf\",\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/#\\\/schema\\\/person\\\/214c5d1dad9f15c48f03128d5cfccdb1\"},\"headline\":\"GDF11\u2014Not So Fast\",\"datePublished\":\"2015-05-24T21:45:26+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2015\\\/05\\\/24\\\/gdf11-not-so-fast\\\/\"},\"wordCount\":1057,\"commentCount\":19,\"publisher\":{\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/#organization\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2015\\\/05\\\/24\\\/gdf11-not-so-fast\\\/#respond\"]}],\"copyrightYear\":\"2015\",\"copyrightHolder\":{\"@id\":\"https:\\\/\\\/scienceblog.com\\\/#organization\"}},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2015\\\/05\\\/24\\\/gdf11-not-so-fast\\\/\",\"url\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2015\\\/05\\\/24\\\/gdf11-not-so-fast\\\/\",\"name\":\"GDF11\u2014Not So Fast - 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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":"GDF11\u2014Not So Fast - 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\/2015\/05\/24\/gdf11-not-so-fast\/","og_locale":"en_US","og_type":"article","og_title":"GDF11\u2014Not So Fast","og_description":"A research report from Novartis may temper our excitement about GDF11, which was a runner-up for Science Magazine&#8217;s 2014\u00a0Breakthrough Of the Year. Bakground \u201cHeterochronic parabiosis\u201d is the sanitized word for sewing together as Siamese twins two animals of the same species but different ages. \u00a0Modern implementation as a research technique was pioneered by Clive McCay ... 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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\/"}]}},"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/pgtN8h-67","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/379","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/comments?post=379"}],"version-history":[{"count":0,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/379\/revisions"}],"wp:attachment":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/media?parent=379"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/categories?post=379"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/tags?post=379"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}