{"id":537,"date":"2016-10-13T03:41:52","date_gmt":"2016-10-13T03:41:52","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=537"},"modified":"2016-10-13T04:52:31","modified_gmt":"2016-10-13T04:52:31","slug":"energizer-lab-worms-keep-on-keeping-on-long-after-they-have-stopped-laying-eggs","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2016\/10\/13\/energizer-lab-worms-keep-on-keeping-on-long-after-they-have-stopped-laying-eggs\/","title":{"rendered":"Energizer lab worms keep on keeping on long after they have stopped laying eggs"},"content":{"rendered":"<p>C. elegans<em> worms live up to 3 weeks, and for the last 2\u00bd weeks, they are post-reproductive, unable to lay fertile eggs because they have run out of sperm to fertilize them. \u00a0Why do they stop fertilizing their eggs, when sperm is metabolically \u2018cheap\u2019? Why has evolution endowed these nematodes with such an extended period of non-productive life? \u00a0In mammals, it is common to speak of the \u201cgrandmother hypothesis\u201d\u2014that human females live on past menopause in order to have time to take care of their grandchildren. \u00a0But worms haven\u2019t been observed to care for their grandchildren. \u00a0<\/em><\/p>\n<hr \/>\n<p>My hypothesis is that, nevertheless, maybe they do. \u00a0The service they provide to their grandchildren is in the form of pheromones.<\/p>\n<p>Pheromones are powerful chemical signals. \u00a0Incredibly small amounts can affect behavior. \u00a0Hormones are chemical signals within the body, and pheromones are like external hormones, directed toward the behavior of other individuals. \u00a0(When the individuals are of a different species, they are called <a href=\"https:\/\/en.wikipedia.org\/wiki\/Kairomone\">kairomones<\/a>.)<\/p>\n<p><i>C. elegans<\/i> is the lab worm that has been so useful in lifespan experiments. \u00a0In the wild, it is thought that these millimeter-long worms live in the ground on rotting fruit or mushroom. \u00a0What is clear is that their life history is exquisitely adapted to boom-and-bust cycles of food availability. \u00a0Like many animals, they live a long time when they are waiting for food to appear, and a short time when they are eating and reproducing. \u00a0And unique to <i>C. elegans<\/i>, the worm\u2019s best trick is to go into a state of semi-dormancy, something like a spore, that can live for months at a time without food or water, and which resists heat, cold, chemical toxins and other insults. \u00a0The spore-like state is called a <a href=\"https:\/\/en.wikipedia.org\/wiki\/Dauer_larva\">dauer<\/a>.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-large aligncenter\" src=\"http:\/\/sage.buckinstitute.org\/wp-content\/uploads\/2015\/03\/oldyoungworm.jpg\" alt=\"Young worm \u2014 Old worm\" width=\"511\" height=\"358\" \/><\/p>\n<p style=\"text-align: center\">Young worm \u2014 Old worm<\/p>\n<p>About 18-24 hours after a worm egg hatches, the stage-3 larva makes a decision whether to go for it, grow and eat and lay lots of eggs, or to become a dauer, to wait and bet on a better opportunity later on. \u00a0My hypothesis starts with the idea that the dauer state represents the only way that a worm can hope to spread its progeny from one food site to another, which is essential if the lineage is to have a long-term future. \u00a0\u201cA chicken is an egg\u2019s idea for making more eggs.\u201d A colony of worms on one food source is a dauer\u2019s way of making more dauers.<\/p>\n<p>Come with me, and explore the dauer\u2019s-eye perspective for a moment. \u00a0You are a fraction of a millimeter long, and you weigh a few billionths of a gram. \u00a0Imagine that you are carried by a bird or animal or by the wind, and you land on a piece of fruit. \u00a0Your lucky day! \u00a0Sensing food and moisture, you morph from the dauer state, turn yourself back into a larva, and you eat and eat, you grow and grow, and you lay several hundred eggs, all endowed for life with a copious food supply.<\/p>\n<p>But if you\u2019re thinking for the long term (all right, worms don\u2019t have brains; but your genes can still be thinking) \u2014 if you\u2019re thinking for the long term, your strategy will be to produce as many dauers as possible from this one piece of fruit. \u00a0Each dauer is a lottery ticket for your future legacy. \u00a0Remember that this piece of fruit is finite, and that when it\u2019s gone, life beyond this one oasis is a very chancy proposition.<\/p>\n<p>In the end, a good measure of your success in the evolutionary game\u2014your fitness\u2014is the number of dauers that come out of this piece of fruit.<\/p>\n<p>With dauer number in mind as a goal, what\u2019s your best strategy? \u00a0Well, for the first generation, it\u2019s to produce several hundred eggs. \u00a0For the second generation, it\u2019s to produce tens of thousands of eggs. \u00a0For the third generation, several million eggs. \u00a0But at that point (or possibly the fourth generation, depending on survival of your grandchildren) it will be important not to keep going with egg-laying, but to start generating dauers. \u00a0The decision that every larva must make should, for optimal fitness, be NOW for the first generation, NOW for the second, NOW, for the third, and LATER for the fourth generation.<\/p>\n<p>But how are you to know that it\u2019s the fourth generation? \u00a0Remember that you haven\u2019t got eyes or ears or a brain. \u00a0You might just keep choosing NOW while there\u2019s food, and wait until there\u2019s no more food to say LATER. \u00a0This would be something you can sense for yourself, but (crucially) this is a flawed strategy. \u00a0The problem is that your population is growing exponentially. \u00a0Exponential population shoots up so quickly that there is no warning at the end. \u00a0<b><i>There might be a billion larvae all competing for the food that was perfectly adequate for the last generation, when the population was a hundred times smaller, but now there are so many mouths to feed that NONE of them will make it to Stage 3 Larvahood, when the worm is mature enough to become a dauer. \u00a0<\/i><\/b><\/p>\n<p>The population that can sense crowding and decide LATER <b><i>before <\/i><\/b>there is a food shortage has a big advantage in the number of dauers that will eventually be produced. \u00a0This is where your grandmother can be of great assistance. \u00a0She has stuck around, though she\u2019s all done laying eggs, and has no prospects for herself, but she and her children can send pheromone signals to their grandchildren, warning them, \u201cDon&#8217;t do it! \u00a0Don\u2019t grow up! \u00a0Take refuge in dauerhood while there\u2019s still time. \u00a0If you wait until we run out of food, it will certainly be too late!\u201d<\/p>\n<p>My theory is that the reason that <i>C. elegans<\/i> goes on living so many days beyond its fertility is that she is sticking around to send pheromone signals to her great grandchildren. \u00a0The 2-3 week lifespan is just sufficient to last through 4 generations. \u00a0The theory makes predictions that are being tested in the Beijing lab of Meng-qiu Dong, where I am a visiting scholar this fall. \u00a0Predictions are<\/p>\n<ol>\n<li>Life span should be extended in the presence of many old worms.<\/li>\n<li>The presence of just a few very old worms should be sufficient to bias a young larva\u2019s decision toward becoming a dauer.<\/li>\n<li>Dauers should be hardy enough to survive the digestive tract of a mouse or bird, so that they can hitch a ride out into the wide world, looking for a new food source.<\/li>\n<\/ol>\n<p><span class=\"embed-youtube\" style=\"text-align:center; display: block;\"><iframe loading=\"lazy\" class=\"youtube-player\" width=\"1200\" height=\"675\" src=\"https:\/\/www.youtube.com\/embed\/VIU249LGOV4?version=3&#038;rel=1&#038;showsearch=0&#038;showinfo=1&#038;iv_load_policy=1&#038;fs=1&#038;hl=en-US&#038;autohide=2&#038;wmode=transparent\" allowfullscreen=\"true\" style=\"border:0;\" sandbox=\"allow-scripts allow-same-origin allow-popups allow-presentation allow-popups-to-escape-sandbox\"><\/iframe><\/span><br \/>\nNictation movie<\/p>\n<p>Here\u2019s a 6-second movie of <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22081161\">nictating<\/a> behavior in a dauer of <i>C japonica<\/i>, a cousin of <i>C. elegans.<\/i> \u00a0Does the dauer look like she\u2019s hiding from predators, or does it look like she\u2019s begging to be eaten? \u00a0My guess is that worms depend on larger animals to reach new food sources that they could never find in a lifetime at their usual squirming pace in the ground.<\/p>\n<p>Prediction (1) has already been tested in the Dong lab, with encouraging results. \u00a0But the other two are stronger consequences of the theory, and I\u2019ll be eager to see how the experiments fare.<\/p>\n<p><b>Note on evolutionary theory and the state of the science<\/b><\/p>\n<p>George Williams laid the foundation for the evolutionary theory of aging that is widely accepted and applied today. \u00a0In his <a href=\"https:\/\/www.jstor.org\/stable\/2406060\">seminal paper of 1957<\/a>, he was bold and astute enough to make 8 predictions that could be used to validate (or falsify) his theory. \u00a0In the intervening years, only 2 of the 8 have been borne out, and 4\u00a0have been flat-out falsified. \u00a0One of the predictions that turned out to be false was that death ought to ensue promptly when the capacity for reproduction is lost. \u00a0Reproductive lifespan and actuarial lifespan should coincide closely, but they don\u2019t.<\/p>\n<p>Williams was, of course, aware that human females are an exception, handily explained by the \u201cgrandmother hypothesis\u201d \u2014 older women are motivated to stick around because rearing young humans takes such a long time that a woman really needs to outlive her fertility. \u00a0But he would be surprised to learn that chickens and whales, partridge and elephants, guppies and yeast cells all have substantial post-reproductive lifespans.<\/p>\n<p>It is to Williams\u2019s credit that he put out a well-reasoned theory and volunteered ways it could be put to the test. \u00a0On the other hand, it reflects badly on the evolutionary scientists who came after him that as the theory was falsified time and again, they clung to the theory, patched it, made excuses for it, but never put it aside to look for a theory that aligns better with experimental reality.<\/p>\n<p>With a lifespan eight times as long as their fertile life, <i>C. elegans <\/i>worms are in a class by themselves. \u00a0Their post-reproductive life has been recognized as a scientific puzzle, and I look forward to finding out if my own theory will stand up to experimental tests.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>C. elegans worms live up to 3 weeks, and for the last 2\u00bd weeks, they are post-reproductive, unable to lay fertile eggs because they have run out of sperm to fertilize them. \u00a0Why do they stop fertilizing their eggs, when sperm is metabolically \u2018cheap\u2019? Why has evolution endowed these nematodes with such an extended period &#8230; <a title=\"Energizer lab worms keep on keeping on long after they have stopped laying eggs\" class=\"read-more\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2016\/10\/13\/energizer-lab-worms-keep-on-keeping-on-long-after-they-have-stopped-laying-eggs\/\" aria-label=\"Read more about Energizer lab worms keep on keeping on long after they have stopped laying eggs\">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":true,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-537","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>Energizer lab worms keep on keeping on long after they have stopped laying eggs - 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\/2016\/10\/13\/energizer-lab-worms-keep-on-keeping-on-long-after-they-have-stopped-laying-eggs\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Energizer lab worms keep on keeping on long after they have stopped laying eggs\" \/>\n<meta property=\"og:description\" content=\"C. elegans worms live up to 3 weeks, and for the last 2\u00bd weeks, they are post-reproductive, unable to lay fertile eggs because they have run out of sperm to fertilize them. \u00a0Why do they stop fertilizing their eggs, when sperm is metabolically \u2018cheap\u2019? 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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":"Energizer lab worms keep on keeping on long after they have stopped laying eggs - 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\/2016\/10\/13\/energizer-lab-worms-keep-on-keeping-on-long-after-they-have-stopped-laying-eggs\/","og_locale":"en_US","og_type":"article","og_title":"Energizer lab worms keep on keeping on long after they have stopped laying eggs","og_description":"C. elegans worms live up to 3 weeks, and for the last 2\u00bd weeks, they are post-reproductive, unable to lay fertile eggs because they have run out of sperm to fertilize them. \u00a0Why do they stop fertilizing their eggs, when sperm is metabolically \u2018cheap\u2019? Why has evolution endowed these nematodes with such an extended period ... 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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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