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Matters Josh Mitteldorf Aging Matters SearchHome Index to This Blog Telomerase Therapies? Post navigation ← Older posts Worms excel in life beyond menopause Posted on May 14, 2024 by Josh Mitteldorf Reply Of the many species that outlive their fertility, lab worms (C elegans) take the cake. They stop laying eggs after two days, but they can go on to live for two more weeks. Did they miss school the day that the teacher was lecturing on Darwinian fitness? Or perhaps do the elders of their community have a message for their grandchildren? In the paper that launched the modern evolutionary theory of aging, George Williams [ 1957 ] predicted: (6) There should be little or no post-reproductive period in the normal life cycle of any species.” Not so long ago, evolutionary scientists thought that human menopause was unique in the biosphere. A whole industry arose explaining thegrandmother effect ”: Playing the game they like best, population geneticists would try to concoct circumstances under which a woman’s selfish genes” could leave more copies of themselves by not reproducing, but instead freeing their bearer to raise her grandchildren, while their mother went out hunting and gathering. Then a literature began to appear in which other animals were discovered to outlive their fertility. But this didn’t stop them. Seldom do facts on the ground discourage an enterprising evolutionary theorist. In several whale species, the female undergoes menopause and continues to live for several decades thereafter [ McAuliffe ]. Elephants, lions, and baboons experience menopause [ Packer ], and all these animals might plausibly be argued to relate to their grandchildren. But some other animals, not so much. As early as 2004 , menopause was recognized as a generalized mammalian trait”. Beyond mammals, hens and guppies both stop laying eggs. Yeast cells stop budding. James Vaupel’s research group published a comprehensive survey of animal life histories” [ 2013 ], in which they charted fertility and mortality over a lifetime for dozens of species of plants and animals. The blue lines map fertility, and the grey background curves show survival. In these 48 plots, C elegans worms, the common lab roundworm, stands out as living most of its life with no fertility at all. Why would that be? My principal contribution to the evolutionary theory of aging has been to cite demographic stability . Population homeostasis doesn’t come for free; in fact all ecosystems would blow up if their constituent species were evolved to live and reproduce as copiously as possible. In general, aging has evolved as nature’s way to prevent population overshoot, to avoid extinctions that come when populations crash, and thus to keep ecosystems stable and productive in the long term. This is my theory paper , with Charles Goodnight, on post-reproductive lifespan as a demographic adaptation. The life cycle of C elegans in nature C elegans worms are hermaphrodites. For the first day of their lives, they are male, and generate a few hundred sperm cells. Then they become female, and start laying eggs, one by one, fertilized by their own stored sperm. But after two days, they run out of sperm and can’t fertilize their own eggs. They become infertile, unless… One worm in a thousand is not a hermaphrodite but a male. It lays no eggs, but produces oodles of sperm, which can fertilize the eggs of a hermaphrodite worm. But she has to be very lucky to find a male, because males are so rare. So this is an interesting footnote, but probably irrelevant to the reason worms are programmed to run out of sperm and discontinue fertility. The vast majority of hermaphrodite worms just live out their lackluster lives. Without sex, is life worth living? When they are not growing in a Petri dish, C elegans worms live on rotting fruit in the wild. One piece of fruit on the ground can feed millions of worms over a period of several weeks. But how are they to get to the next piece of fruit? If the worm is fat and happy, it lives 2 to 3 weeks. But if the worm is starved, it has a special adaptation. When food is scarce, it can go into a diapause stage called dauer , in which it doesn’t eat and its metabolic rate is very low. As a dauer, the worm can live for many months. The dauer can be ingested by a bird and survive digestion. Carried by the wind or hitching a ride in a bird’s intestine, dauers are the worm’s plan for getting from one piece of fruit to the next. The fitness” of a worm is probably better measured by its probability of finding a new piece of fruit than by the number of offspring it produces. Fitness is a property of a worm colony, not of a single worm. The fitness of a colony is related to the number of dauers that are sent out to explore the environment for the next piece of fruit. Do the math — at several hundred worms per generation, the first three generations will do fine. They will be able to gorge themselves on fruit. But the fourth generation would be hundreds of times larger. The worms would start to grow, only to find that there are so many of them competing for the fruit that none have a chance to grow to maturity. This is why the ability to dauer is not just useful but essential to the worms’ collective survival. Larval worms detect food scarcity, and they flip a switch into dauer mode. They cast their future to the wind, or commit themselves to the gut of a hungry bird. There is a danger, though, that they might miss their timing. If they are starved right out of the egg, the worm is not yet large enough to form a dauer. But one day out of the egg, the worm is already committed to maturity, and it is too late to dauer. The dauering window is just a few hours long. It is easy to miss. Here is where grandma can help. In a worm colony that is in its fourth generation, there are already hundreds of thousands of elder worms, post-reproductive but still squirming. These worms saturate the nest with dauer pheromone . The pheromone signals the hatchlings of the fourth generation that, even though it may seem that there’s plenty of food for now, the generation size is so high that the food supply is in danger of being exhausted before they can grow to maturity. The pheromone encourages the young larvae to go into dauer rather than take their chances on maturity and reproduction in present conditions. Dauer pheromone from the oldest worms is a signal both of crowding and of colony age. Exponential mathematics is what is threatening the worm population, and exponential mathematics is what potentiates the enormous increase in dauer pheromone that inform the larvae that their best prospects are to leave home and seek their fortune in the countryside. This last paragraph is my personal theory, not yet fully confirmed. For a decade, I have been looking for someone to actually measure dauer pheromone from elder worm populations, and no one has taken up the challenge in this form. But from two labs where I have worked, there is partial confirmation. These are in the Beijing National Institute of Biological Sciences (Meng-qiu Dong and Wu Gang) and at Washington University of St Louis (Kerry Kornfeld and Andrea Scharf). Evidence for the grandmother worm theory NIBS Beijing In 2017, while I was a visiting scholar at the National Institute for Biological Sciences in Beijing, my host, Meng-qiu Dong , was kind enough to design two experiments with grad students Wu Gang and Peng Lei. First they raised infertile worms synchronized by age, so they could extract liquid from their growth medium when all the worms were a fixed age. They confirmed that dauer pheromone could be extracted from the medium, and that the quantity peaked for 5-day-old worms. Larvae grown in the medium where 5-day-old worms had lived were more likely to dauer than larvae in a control medium. 5-day-old worms are grandparents, but not yet great grandparents. Second, they grew worms to old age on half a Petri dish, and then grew a fresh generation...