{"id":101,"date":"2013-05-05T23:21:03","date_gmt":"2013-05-05T23:21:03","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=101"},"modified":"2013-05-05T23:21:03","modified_gmt":"2013-05-05T23:21:03","slug":"role-of-the-nervous-system-in-deciding-how-long-we-live","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/05\/05\/role-of-the-nervous-system-in-deciding-how-long-we-live\/","title":{"rendered":"Role of the Nervous System in deciding How Long we Live"},"content":{"rendered":"<p dir=\"ltr\"><em>A new report this week about signals from hypothalamus reminds us that some of the biggest influences on longevity are mediated through the nervous system. \u00a0To this extent, the decision about how long to live comes from a calculation made in the brain. \u00a0The new research suggests a hormone known as GnRH as a relatively simple signal by which aging might be slowed, and another signal called NF-kappa-B promotes aging and might be blocked to slow aging. \u00a0 \u00a0<\/em><\/p>\n<p>In genetic experiments with worms in the 1990s, <a href=\"http:\/\/en.wikipedia.org\/wiki\/Daf-2\" target=\"_blank\">DAF-2<\/a> was one of the first genes discovered that curtails life span. \u00a0Delete the DAF-2 gene, and the worm lives longer. \u00a0But by what mechanism? \u00a0No one had the least idea. \u00a0Gary Ruvkun\u2019s lab at Harvard found a way to ask a fundamental question , using genetic manipulations that were just becoming available at the time.<\/p>\n<p dir=\"ltr\">Normally, of course, every cell in the body has exactly the same DNA. \u00a0But Ruvkun was able to prepare \u201cmosaic\u201d worms with different genes in different areas of the body. \u00a0Lab worms are simple creatures with just three kinds of tissue comprising most of their 959 cells. \u00a0So he had three kinds of worms, with<\/p>\n<ul>\n<li>DAF-2 genes only in the intestinal and digestive cells<\/li>\n<li>DAF-2 genes only in the muscle cells<\/li>\n<li>DAF-2 genes only in the nerve cells<\/li>\n<\/ul>\n<p dir=\"ltr\">What he learned (<a href=\"http:\/\/stke.sciencemag.org\/cgi\/content\/abstract\/sci;290\/5489\/147\">2000<\/a>) was that it was only through the nerve cells that DAF-2 shortens life span.<\/p>\n<p>This was the first indication that maybe there are nerve networks that calculate life span, based on many sensory inputs, internal and external. \u00a0Maybe the length of our lives is decided in our neurons. \u00a0That\u2019s an over-statement to be sure, but what has become clear is that the nervous system has a substantial role in dictating life span, and this is true in mammals as well as worms.<\/p>\n<p>The biggest factor affecting life span from the outside is availability of food. Of course, it\u2019s a conundrum for the traditional view of aging (based on accumulated damage): why is the body able to protect itself from damage better when it is starving? \u00a0Biologists have looked and looked for metabolic effects, and traced the biochemistry through the metabolism of the blood-sugar regulating hormone insulin, and the fat cells that signal to ignite self-destructive inflammation. So we are able to understand how, but not why the metabolism is not able to protect itself from these effects when food is plentiful..<\/p>\n<p>But it\u2019s not about \u201cable\u201d so much as \u201cwilling\u201d. \u00a0The body is programmed to die on schedule when the population has what it needs to be fruitful and multiply, but to hold off the genetic source of death at the individual level when famine is more of a threat than overpopulation. \u00a0As if to underscore that this is a choice, rather than a direct consequence of biochemistry, life extension through caloric restriction is found to be mediated through the nervous system. \u00a0The UCSF laboratory of Cynthia Kenyon has reported (<a href=\"http:\/\/www.nature.com\/nature\/journal\/v402\/n6763\/abs\/402804a0.html\" target=\"_blank\">1999<\/a>) that destroying the worm\u2019s tiny chemical sensor, the smeller\/taster that detects the presence of food, can extend the worm\u2019s life span even as though it were starving even though it has plenty to eat.<b><b>\u00a0<\/b><\/b><\/p>\n<p dir=\"ltr\">Soon it was discovered that, in mammals, too, the signals that mediate the effect of food in shortening life span are also coordinated through the central nervous system. \u00a0In response to eating, the body secretes insulin to make sure that blood sugar doesn\u2019t get dangerously high. \u00a0But in addition to this short-term effect, the insulin signaling has a long-term effect that hastens the aging process. \u00a0Holzenberger (<a href=\"http:\/\/www.sciencedirect.com\/science\/article\/pii\/S053155650400292X\">2004<\/a>)\u00a0first suggested that the hypothalamus is the switchboard in the brain from which endocrine signals are sent that shorten life span in response to food. \u00a0In a <a href=\"http:\/\/www.biochemj.org.libproxy.mit.edu\/bj\/418\/0001\/4180001.pdf\">2009 review<\/a>,\u00a0Susan Broughton and Linda Partridge summarized the case against the CNS as culprit in translating the body\u2019s insulin signals into a pro-aging message. \u00a0It\u2019s complicated, they add, because the nerves themselves seem to benefit from insulin signaling, so that insulin might protect the aging CNS, even as the CNS does the dirty work of generating the signals that age the rest of the body. \u00a0They express hope that the protective benefit of insulin can be separated from the pro-aging signal. \u00a0The <a href=\"http:\/\/stke.sciencemag.org\/cgi\/content\/abstract\/sci;317\/5836\/369\" target=\"_blank\">knockout experiment<\/a> (excuse the pun) was performed in 2007 in the Harvard lab of Morris White. \u00a0\u00a0A gene that receives insulin signals was knocked out not in the whole mouse but just in the brain (by now mosaic experiments are routine). \u00a0The result was mice that are obese and diabetic and insulin-resistant but still their life spans were extended, compared to controls. \u00a0Despite being published in Science, this experiment has not received attention commensurate with its promise, perhaps because its methods were so technical.<\/p>\n<p dir=\"ltr\">Outside of diet, some of the primary factors that predict life span in humans are <a href=\"http:\/\/europepmc.org\/abstract\/MED\/12785422\/reload=0;jsessionid=lcp5xqJewHMw9aAcLjK8.6\">social<\/a>. \u00a0People live longer when they are needed, when they have in close family ties, when they have <a href=\"http:\/\/www.sciencedirect.com\/science\/article\/pii\/0277953694903751\" target=\"_blank\">status and importance in their communities<\/a>. \u00a0This seems to be true even after the access to good food, healthy environments, and better medical care are factored out. \u00a0And it may be true in other <a href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajp.1350150308\/abstract\">non-human primates<\/a>. \u00a0This doesn&#8217;t tell us anything about mechanism, but again it is suggestive of a central role for the brain in regulation of aging.<\/p>\n<p>This brings us to the results published this week\u00a0<a href=\"http:\/\/www.nature.com\/nature\/journal\/vaop\/ncurrent\/full\/nature12143.html\">in Nature<\/a>\u00a0from the lab of Dongsheng Cai at Einstein College of Medicine in New York. \u00a0Excess inflammation has been recognized for a long time as a direct mechanism of aging. \u00a0Inflammation increases cancer risk, destroys arteries, and plays a role in Alzheimer\u2019s disease (<a href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/01\/14\/how-can-we-stop-killing-ourselves\/\">here is my blog post on the subject<\/a>).<\/p>\n<p dir=\"ltr\">The new study shows that there is also an indirect effect of inflammation that magnifies its pro-aging effect. \u00a0Inflammation is detected in the hypothalamus<a href=\"#fn\">*<\/a>, and pro-aging signals are sent out as a result. \u00a0Since these signals further increase inflammation, this could be one of those self-reinforcing loops that accelerate our demise, and are relatively easy to disrupt via medical intervention. \u00a0(Cai spoke of \u2018cascading benefits\u2019.) \u00a0The mechanism described in Cai\u2019s paper involve two more ingredients from the genetical alphabet soup: \u00a0<a href=\"http:\/\/en.wikipedia.org\/wiki\/NF_kappa_B\">NF-kappa-B<\/a> is emitted in response to danger, and switches on the gene transcription in a cell in a manner appropriate to emergency response. NF-kappa-B increases with age and promotes higher levels of inflammation \u2014 Boooo! \u00a0<a href=\"http:\/\/en.wikipedia.org\/wiki\/Gnrh\">GnRH<\/a>\u00a0is a signal that commands the reproductive cycle (M as well as F) and incidentally works to protect the body from aging \u2014 Yeaaa! \u00a0Inflammation increases NF-kappa-B in the hypothalamus, and this, in turn, reduces the flow of GnRH.<\/p>\n<p dir=\"ltr\" style=\"padding-left: 30px\">When the researchers added GnRH to the hypothalamuses of old mice, they saw that it promoted adult neurogenesis. When they injected mice with GnRH, the mice showed reduced signs of aging. \u00a0(from <a href=\"http:\/\/www.the-scientist.com\/?articles.view\/articleNo\/35411\/title\/Brain-Is-Command-Center-for-Aging\/\">The Scientist<\/a>)<\/p>\n<p dir=\"ltr\">The one-line take-home is that blocking NF-kappa-B in the hypothalamus increased the life span of mice by 20% (<a href=\"http:\/\/www.einstein.yu.edu\/news\/releases\/894\/brain-region-may-hold-key-to-aging\/\">press release<\/a>).\u00a0 And that\u2019s as close as I can come to a simple story with a single magic bullet.<\/p>\n<p>\u00a0&#8212;&#8212;&#8212;&#8212;-<\/p>\n<p dir=\"ltr\"><a name=\"fn\"><\/a>*The\u00a0<a href=\"http:\/\/en.wikipedia.org\/wiki\/Hypothalamus\">hypothalamus<\/a>\u00a0is a tiny organ in the lower midbrain that takes nerve signals (electrical) and transduces them into hormonal signals (chemical) for transmission throughout the body.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A new report this week about signals from hypothalamus reminds us that some of the biggest influences on longevity are mediated through the nervous system. \u00a0To this extent, the decision about how long to live comes from a calculation made in the brain. \u00a0The new research suggests a hormone known as GnRH as a relatively &#8230; <a title=\"Role of the Nervous System in deciding How Long we Live\" class=\"read-more\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/05\/05\/role-of-the-nervous-system-in-deciding-how-long-we-live\/\" aria-label=\"Read more about Role of the Nervous System in deciding How Long we Live\">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_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":"","jetpack_post_was_ever_published":false},"categories":[1],"tags":[],"class_list":["post-101","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.6 (Yoast SEO v27.6) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Role of the Nervous System in deciding How Long we Live - 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\/2013\/05\/05\/role-of-the-nervous-system-in-deciding-how-long-we-live\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Role of the Nervous System in deciding How Long we Live\" \/>\n<meta property=\"og:description\" content=\"A new report this week about signals from hypothalamus reminds us that some of the biggest influences on longevity are mediated through the nervous system. \u00a0To this extent, the decision about how long to live comes from a calculation made in the brain. \u00a0The new research suggests a hormone known as GnRH as a relatively ... Read more\" \/>\n<meta property=\"og:url\" content=\"https:\/\/scienceblog.com\/joshmitteldorf\/2013\/05\/05\/role-of-the-nervous-system-in-deciding-how-long-we-live\/\" \/>\n<meta property=\"og:site_name\" content=\"Josh Mitteldorf\" \/>\n<meta property=\"article:published_time\" content=\"2013-05-05T23:21:03+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=\"6 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2013\\\/05\\\/05\\\/role-of-the-nervous-system-in-deciding-how-long-we-live\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2013\\\/05\\\/05\\\/role-of-the-nervous-system-in-deciding-how-long-we-live\\\/\"},\"author\":{\"name\":\"Josh Mitteldorf\",\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/#\\\/schema\\\/person\\\/214c5d1dad9f15c48f03128d5cfccdb1\"},\"headline\":\"Role of the Nervous System in deciding How Long we Live\",\"datePublished\":\"2013-05-05T23:21:03+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2013\\\/05\\\/05\\\/role-of-the-nervous-system-in-deciding-how-long-we-live\\\/\"},\"wordCount\":1211,\"commentCount\":8,\"publisher\":{\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/#organization\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2013\\\/05\\\/05\\\/role-of-the-nervous-system-in-deciding-how-long-we-live\\\/#respond\"]}],\"copyrightYear\":\"2013\",\"copyrightHolder\":{\"@id\":\"https:\\\/\\\/scienceblog.com\\\/#organization\"}},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2013\\\/05\\\/05\\\/role-of-the-nervous-system-in-deciding-how-long-we-live\\\/\",\"url\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/2013\\\/05\\\/05\\\/role-of-the-nervous-system-in-deciding-how-long-we-live\\\/\",\"name\":\"Role of the Nervous System in deciding How Long we Live - 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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":"Role of the Nervous System in deciding How Long we Live - 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\/2013\/05\/05\/role-of-the-nervous-system-in-deciding-how-long-we-live\/","og_locale":"en_US","og_type":"article","og_title":"Role of the Nervous System in deciding How Long we Live","og_description":"A new report this week about signals from hypothalamus reminds us that some of the biggest influences on longevity are mediated through the nervous system. \u00a0To this extent, the decision about how long to live comes from a calculation made in the brain. \u00a0The new research suggests a hormone known as GnRH as a relatively ... 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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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