“If you can slow down the decline in function, then you\u2019ve slowed down aging.”<\/p>\nStephen Treaster<\/cite><\/blockquote>\n\n\n\n Even without an enchanted elixir, humans are already really good at living a long time. We\u2019re the longest-lived terrestrial mammal, outpacing our nearest relatives, chimpanzees and bonobos, by a decent margin. We stay healthy for a long time, too. That\u2019s one reason why extending the amount of time we can experience a high quality of life is so hard. When you already perform exceptionally, every further bit of performance needs to be fought for, found on the margins. \u201cIt\u2019s like we\u2019re already a world-class sprinter,\u201d Austad said. Expecting a high school track coach to help us get better isn\u2019t going to work. We need to learn from the best \u2014 and some of our friends in the animal kingdom are like Usain Bolt and Flo-Jo combined.<\/p>\n\n\n\n The hydra is the most extreme example, but all six biological kingdoms include organisms that have evolved strategies for longevity. Pando, a quaking aspen clone<\/a> in Utah, has lived for thousands of years. It\u2019s part of an eternal Eden of trees, seaweeds, and fungi whose lives can last well into the six figures. Greenland sharks, those massive denizens of the frozen depths, are estimated to live between 200 and 400 years. The bowhead whale can clock a couple hundred itself, making it the longest-lived mammal. All of these may be mere babes compared to some under-the-seafloor dwelling microorganisms estimated to be millions of years old.<\/p>\n\n\n\n So, while we\u2019re no closer to a magic wellspring than the conquistadors were, Austad believes we are <\/em>close to understanding enough about aging to tinker with it \u2014 thanks to our friends in the animal kingdom.<\/p>\n\n\n\n Aging, for many researchers like Austad, isn\u2019t really about the passage of time. How long an organism is alive \u2014 its chronological age \u2014 is a useful and easy-to-understand metric. But few would argue that tacking on 10 years would be desirable if that decade were spent with a diminished quality of life.<\/p>\n\n\n\n A major goal of aging research is to increase healthspan, the amount of time we live with what could generally be considered a high quality of life. Rather than the years, days, hours, minutes, and seconds that mark chronological aging, researchers are focused on how long things work well: their biological age. It\u2019s a measure of an organism\u2019s body or body part based on how well it functions. \u201cIf you can slow down the decline in function, then you\u2019ve slowed down aging,\u201d said Stephen Treaster, a scientist at the Gloucester Marine Genomics Institute, who is founding a lab to extend his pre- and postdoctoral work.<\/p>\n\n\n\n Chronological age can correlate with biological age, but they don\u2019t move in lockstep \u2014 the comparatively compressed lifespan of pets provides a painful example of that. When it comes to studying animals in the wild, however, lifespan can be used as a proxy measurement for healthspan. The reasoning is as graceful as it is brutal: When biological decline hits, wild animals tend to die.<\/p>\n\n\n\n It’s in the outliers where the answers may lie.<\/p><\/blockquote><\/figure>\n\n\n\n The differences between biological and chronological age highlight an uncomfortable truth: Aging doesn\u2019t follow a tidy blueprint. Unlike rocket science or mechanical engineering, biology is messy. The field is, by definition, alive and changing. But there are rough guidelines when you look at life as a whole. <\/p>\n\n\n\n Smaller species of animals generally have shorter lifespans, although, within species, larger individuals don\u2019t last as long. Researchers have found that caloric restriction \u2014 reducing daily calorie intake, but not to the point of causing malnutrition \u2014 slows aging across vast swaths of life, from yeast to primates. For cold-blooded creatures, living in colder conditions \u2014 like the kind you can find underwater \u2014 seems to slow decline. Think the Greenland shark, spending its many days a few degrees from freezing.<\/p>\n\n\n\n Carving out a life in a relatively protected environment can lead to a longer lifespan. Treaster gives two classic examples: bats and naked mole rats. Both live much longer than you would expect from their evolutionary history and body size, and bats make their bones by flying, a metabolically costly process. But they\u2019ve both found themselves in very safe spaces. Bats take to the skies and mostly come out at night; naked mole rats spend their lives underground. Once you\u2019ve found your safe spot, Treaster said, \u201cyou can start evolving [an] extended lifespan.\u201d<\/p>\n\n\n\n These overarching trends can help us understand biological aging writ large, but they\u2019re not perfect. And it’s in the outliers where the answers may lie. \u201cMy approach to this whole problem is tapping into these exceptionally long-lived animals,\u201d Treaster said. \u201cBecause they already know how to do it.\u201d<\/p>\n\n\n\n Ming<\/a> certainly knew how to do it. The ocean quahog, a member of a tasty species of long-lived clam, was dredged up from a depth of around 270 feet off the cold coast of Iceland by the research vessel Bjarni S\u00e6mundsson in 2006. Researchers determined the clam was 507 years old \u2014 making it the longest-lived individual animal that we know of.<\/p>\n\n\n\n Ocean quahogs live in a fairly cold and stable environment, but they are small \u2014 a perfectly imperfect anomaly for Treaster to study. In 2009, while a doctoral student in Austad\u2019s lab, he began his research on the species, trying to tease out just how they survive so long. <\/p>\n\n\n\n Genomic sequencing was still expensive at the time, and even if he mapped out the ocean quahog\u2019s code, there would have been nothing to compare it to, Treaster said. Despite making up a huge percentage of the tree of life, bivalves like clams, oysters, and scallops are incredibly understudied outside the kitchen \u2014 there could be many secrets between those shells.<\/p>\n\n\n\n The key to the ocean quahog\u2019s long life seems to lie in its ability to maintain the integrity of its proteins through the centuries. Proteins are essentially the functional units of organisms, underlying all the processes by which we define life. They\u2019re the most basic point of failure when it comes to biological decline and possibly the most basic level of biological aging. \u201cCells can fail,\u201d Treaster said, \u201cbut they\u2019re failing because their proteins are failing. Because cells are just a bunch of proteins \u2026 and some other stuff,\u201d he added, laughing.<\/p>\n\n\n\n That led Treaster to a new hypothesis: Maybe long-lived species are better at maintaining their functional proteins than short-lived ones. Perhaps there was some kind of specific <\/strong>small molecule that helped clams like Ming maintain their proteins. To find out, he ran protein stability tests in long-lived species of clams and compared them to short-lived species of clams. The result: The long-lived clams had more stable proteins. <\/p>\n\n\n\n If scientists could isolate the method by which the ocean quahog maintains its protein integrity, they could translate into a therapeutic more easily. \u201cEspecially given that so many human pathologies are, at their heart, a protein-structure failure,\u201d Treaster said.\u00a0<\/p>\n\n\n\n Clam therapy is not quite here yet, but Treaster and his team are continuing their research on ocean quahogs outside the confines of the lab. Off the coast of New England, Ming\u2019s relatives can live for 200 years, while other clams manage to last for only a few. Unlike in 2009, sequencing the species\u2019 genomes is now an option, and by comparing those results and the clams\u2019 developmental timing, they hope to figure out the secret to the mollusks\u2019 longevity.<\/p>\n\n\n\n Bats and naked mole rats may owe their unusually long lives to their ecological niches. By reducing the pressure to procreate posthaste, the habitats may have allowed evolution to focus on genes that helped the species stick around for a long time, not just a good time. <\/p>\n\n\n\n But nature has given us examples of creatures that have vastly different lifespans, despite being closely related and living in the same environments. This suggests there\u2019s more to a long life than choosing the right home base. To examine this potential link between environment, genetics, and longevity, Treaster turned again to the sea.<\/p>\n\n\n\n Nature\u2019s longevity secrets are scattered across the evolutionary map.<\/p><\/blockquote><\/figure>\n\n\n\n Rockfish are a family of a hundred or so species of bony fish with a large lifespan discrepancy. Some can live for a couple centuries, others for a couple years. Rockfish on both sides of that spectrum can be found in the same underwater environments, suggesting that where they live is not the most crucial factor in lifespan. Evolution-wise, rockfish are pretty recent additions to the ocean, independently evolving longer or shorter lifespans multiple times in only 8 million years. That means the various species are relatively closely related, making for a cleaner comparison of their genes\u2019 role in how long they live.<\/p>\n\n\n\n The prevailing theory on rockfish was that they began as a short-lived creature, with some members of the family later evolving staying power. Treaster discovered the opposite \u2014 that rockfish actually began as long-lived creatures, with some species evolving to have shorter lives but the ability to reproduce faster. <\/p>\n\n\n\n With that in mind, he began to look at recent genetic changes in short-lived rockfish species compared to long-lived ones. He found that genes controlling for two different metabolic pathways seem to regulate rockfish lifespan. When he compared one of those pathways to its analog in humans, he found that changes in the genes were tied to longer life in us as well \u2014 making them a strong target for healthspan extension therapies. <\/p>\n\n\n\n It\u2019s a surprising result. The two species share genetic pathways that influence their lifespans \u2014 even though they diverged 400 million years ago. It\u2019s also more evidence that nature\u2019s longevity secrets are scattered across the evolutionary map.<\/p>\n\n\n\n Even if rockfish\u2019s lifespans aren\u2019t wholly dependent on their surroundings, the fact that the oceans seem to teem with long-lived species \u2014 from clams to whales \u2014 suggests that environment does matter. As for what makes the ocean so conducive to a long life, it\u2019s generally colder than on land, and it\u2019s also comparatively safe and stable. Shelter, stability, temperature, and mortality risk are all directly tied to lifespan. <\/p>\n\n\n\n \u201cThere are no sudden temperature swings, few predators, and hardly any disturbances,\u201d said Owen R. Jones, <\/strong>associate professor in the Department of Biology at the University of Southern Denmark. \u201c<\/strong>Some good studies support this, for example, showing that maximum recorded longevity increases with depth. And depth is associated with environmental stability.\u201d<\/p>\n\n\n\n “What\u2019s different now is not so much in our biology, but our ability to keep ourselves safe.”<\/p>\nOwen R. Jones<\/cite><\/blockquote>\n\n\n\n We\u2019ve got terrestrial examples of the importance of safety and stability, too. Galapagos tortoises on predator-free islands can crack a century of life. Cave salamanders \u2014 whose cool, stable, subterranean homes echo some ocean conditions \u2014 can do the same. <\/p>\n\n\n\n Humans fall into this category, too, albeit in a unique way. In the time we\u2019ve been able to track age accurately, our current maximum lifespan hasn\u2019t really changed much: 115 to 120 years. Contrary to popular perception, a baby born 20,000 years ago with the same genes as you likely had the same biological shot of reaching 80, Jones said. The difference is that modern babies are much more likely to live long enough to get that shot. For much of human history, high infant mortality rates suppressed the average lifespan. \u201cWhat\u2019s different now is not so much in our biology, but our ability to keep ourselves safe,” Jones said. \u201cClean water, antibiotics, vaccines, sewage systems, modern housing, controlled food supply, social safety nets.\u201d<\/p>\n\n\n\n It\u2019s the same reason zoo animals often live longer than their wild counterparts. <\/p>\n\n\n\n Most creatures, however, still live at the mercy of their surroundings, which makes them valuable subjects for understanding how the environment impacts biology and biology impacts aging. The problem is that it\u2019s really hard to study animals in the wild. And as Austad pointed out, \u201cA laboratory environment is unbelievably artificial.\u201d In many cases, lab researchers are limited to studying only cells, too, and not whole animals, due to cost and logistics. That may be one of the reasons why attempts to translate lab findings to real-world use cases can be so unsuccessful. <\/p>\n\n\n\n Luckily, there is one animal model for aging that not only shares our environment but also can test one of the few compounds that just might combat aging in humans. And you may be petting one right now.<\/p>\n\n\n\n The domestic dog has a lot going for it as a model of human aging<\/a>. It has a comparatively compressed lifespan, which makes longitudinal studies \u2014 ones that observe a subject at different timepoints in life \u2014 more feasible. Dogs share many of the same aging pathologies humans do, such as obesity, arthritis, and diabetes. We have centuries\u2019 worth of veterinary understanding to draw on when assessing how healthy and happy pups are. And dogs have traditionally been good models for safety and toxicity testing of human treatments. Several medical breakthroughs, including the discovery of insulin, stemmed from canine research.<\/p>\n\n\n\n The Dog Aging Project<\/a>, an initiative co-founded in 2014 by biogerontologist Matt Kaeberlein, looks to leverage dogs\u2019 advantages as a model of human aging \u2014 while helping dogs live healthier and longer. So far, the project has enrolled 50,000 dogs and sequenced the genomes of about 10,000 of them, producing a large amount of data. Kaeberlein, who is also the CEO of healthspan technology company Optispan<\/a>, said the group tries to collect new data on study participants every year, too, \u201cto see how the dog\u2019s health is changing over time.\u201d Researchers can then use that data to try to answer questions about which environmental and genetic factors have the strongest associations with functional decline, age-related diseases, and mortality. The combination of the study\u2019s large population size and long horizon helps researchers reach stronger correlations between those variables and what is happening as the dogs age: diseases, declines, and death.<\/p>\n\n\n\n Part of drawing the strongest correlations possible is making sure that you have a wide variety of subjects. So the Dog Aging Project invites every type of dog to join its \u201cpack.\u201d They can be any size, any breed or mix of breeds, healthy and spry, or living with a chronic disease. Owners need to be based in the U.S. and have a solid estimate of their dog\u2019s age, but those are basically the only limiting factors. They can nominate their dogs by visiting the project\u2019s website to complete the extensive Health and Life Experiences Survey<\/a>, which asks about everything from the dog\u2019s diet to how much exercise they get to who they share their home with. This data gets combined with larger environmental factors, like the air and water quality of their home, based on their ZIP code. The end result is a pretty robust picture of each pack member.<\/p>\n\n\n\n The dogs that were fed once a day were at lower risk of developing all 10 diseases. The project enrolls some dogs from within this massive pack in smaller groups set up to study specific things \u2014 two subsets, for example, were open to all types of dogs for genomic and biochemical study. The group says it has already identified a few potential correlating factors for biological aging that look interesting enough to warrant further research. <\/p>\n\n\n\n One is feeding frequency, which the team chose to analyze based on the literature \u2014 and general enthusiasm \u2014 surrounding intermittent fasting, a dietary pattern that switches between eating and fasting on a regular schedule. Kaeberlein realized that dogs could make for a good model for studying this variable because people naturally feed their pets on different schedules. Some dogs eat twice a day, while some eat three times. Other dogs can just graze all day.<\/p>\n\n\n\n \u201cWe just asked a very, very simplistic question,\u201d Kaeberlein said: Are dogs fed only once per day different from dogs fed <\/em>more than once when it comes to the likelihood of developing 10 age-related diseases? \u201cI didn\u2019t think it was going to work because I\u2019m not a big believer in intermittent fasting,\u201d he added, but the dogs that were fed once a day were at lower risk of developing all 10 diseases. In seven or eight of the diseases, the difference was statistically significant.<\/p>\n\n\n\n Again, this shows correlation, not causation. But could a once-daily feeding schedule be slowing biological aging and lowering disease risk? Maybe. Or maybe dogs fed less frequently are less likely to be obese, and in reality, obesity \u2014 not feeding frequency \u2014 drives the risk. Rather than an answer, a study like this gives researchers a signal, a chance to generate hypotheses and then go back to sniffing for possible answers.<\/p>\n\n\n\n “I\u2019ve been in science a long time. You learn to recognize results that look real, and that result looks very strong.”<\/p>Matt Kaeberlein<\/cite><\/blockquote><\/figure>\n\n\n\n While the once-a-day devourers had a lower risk of developing dementia, age was the greatest risk factor, just like it is in humans \u2014 \u201ca good sanity check,\u201d Kaeberlein joked. But activity level also stood out as an important correlate for dementia risk \u2014 more activity equaled lower risk \u2014 as did sterilization status: Intact dogs had a 21% higher risk of developing the condition.<\/p>\n\n\n\n Across the pack, the team found that mixed-breed dogs lived, on average, about one year longer than purebred dogs when they controlled for body size \u2014 generally, the bigger the dog, the shorter the life. One possible reason for the difference? Inbreeding of purebreds, which may put them at higher risk of various genetic conditions.<\/p>\n\n\n\n Whether you have a mutt or a show dog, though, feeding them once a day could be the easiest way to increase their chance of a long healthspan. \u201cI\u2019ve been in science a long time,\u201d Kaeberlein said. \u201cYou learn to recognize results that look real, and that result looks very strong.\u201d<\/p>\n\n\n\nWildlife-span <\/h3>\n\n\n\n
The old clam and the sea<\/h3>\n\n\n\n
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Rockfish of ages<\/h3>\n\n\n\n
Location, location, location<\/h3>\n\n\n\n
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Paws and effect<\/h3>\n\n\n\n
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