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What animals can tell us about human aging

Scientists who want to understand why some of us are living longer and healthier have traditionally focused on studying the centenarians of the "blue zones" of the world, such as Okinawa, Japan, or Ikaria, Greece, where locals regularly beat longevity records.

Emma Teeling, Irish biologist for bats, thinks the answer can be found among bats in the belfries of fairy tales of the Gothic cathedrals of Brittany, France. Each spring, she and her team travel there to trap hundreds of brown bats and brown bats to collect their blood so they can sequence their DNA. Since mothers return to their birthplace several times to give birth, cathedrals are an ideal setting for restoring the same bats and studying their aging.

Teeling is convinced that these tiny Myotis myotis bats, which weigh no more than 1.6 ounces, have aging superpowers that offer clues to improve human health. "Bats can tolerate viruses, rarely catch cancer and show no signs of aging," says Teeling from University College Dublin. "They are also living much longer than expected, given their small size."

Of the 19 species of mammals that survive human life after adjusting for body mass, 18 are bats. She documented a bat trapped in adulthood and captured 41 years later – a remarkable feat of getting old if she measured about a third of the size of a mouse, which only lives a few years.

"I wanted to understand the molecular mechanisms that kept them healthy," says Teeling, who recently launched Bat1K, an initiative to sequence the genomes of all 1,300 species of bats. The telomeres of bats, the protective tips of chromosomes which, in most mammals – including humans – shorten with age, are of particular interest.

However, Telling's team found that the telomeres of Myotis myotis kept the same size year after year. To solve the mystery, they compared the 225 genes associated in the cell path of bats with those of 52 other mammals and discovered two genes that only existed in bats and which they thought could be repair the damage to DNA during aging,

In one According to an article published this month, they reported sequencing 1,700 billion base pairs of RNA from 150 bats in order to detect the small regulatory genes involved in these aging pathways. The future goal: "Manipulate these pathways in humans through drugs or potentially gene therapy to ultimately limit and slow down the diseases associated with aging in humans," says Teeling.

Marmosets, other primates

Animals have long been a fundamental part of medical research – more than 140,000 were used in the United States in 2107, according to the Department of Agriculture – for everything from testing drugs to surgical techniques before they start. to be experienced on the human. Yet, a new wave of researchers is looking at the unique biology of some animals to see how we could live and thrive longer.

"Aging research is no longer about increasing longevity, but about increasing our lifespan, which is the length of time people can live a healthy life." Says Corinna Ross, primatologist at the Texas Biomedical Research Institute in San Antonio. She studies aging in marmosets. "The goal is not to increase the number of 120-year-olds living in retirement homes. We want more than 80 and 90 years living independently. "

Scientists have always relied on worms and rodents for their studies on aging. Yet an article published in 2017 by National Institute on Aging researchers argues for a greater focus on non-human primates that share 92% of the genes with humans and have an aging process that looks more like to human experience. "

Although the National Institutes of Health announced in 2015 that they would stop using chimpanzees in biomedical studies, the researchers say that monkeys and rhesus marmosets are useful models for learning more about them. mechanisms that "lead to the universally observed decline, from one species to the other".

For Ross, marmosets are ideal research subjects because they have a similar metabolism and catch age-related diseases similar to those of humans. Marmosets can live up to 22 years, but they show signs of aging, such as greater stretching and less frequent leaps from one branch to the other, as early as age 10 years old.

"They are aging five times faster than humans. This means that we can study aging interventions in a much shorter time frame than in humans, "says Ross. For example, she is evaluating the effect on marmosets of an immunosuppressive drug called rapamycin that would prolong the life of mice to determine if it could delay the cognitive decline and fragility of monkeys.

These primates also offer a unique window on women's aging as they have a similar reproductive cycle and offer the opportunity to study what happens after menopause. Rhesus monkeys, in particular, have a 28-day menstrual cycle and experience the end of their fertility at about the same time in their lives. (They live up to 40 years in captivity.)

The neuroscientist Yuko Hara was curious to know why some Rhesus female monkeys were mentally sharper than other monkeys when they aged and if estrogen could play a role. As part of her research at Mount Sinai's Icahn School of Medicine, she and her team discovered that monkeys given hormone therapy after menopause had better cognitive performance than those who did not.

The important thing in this research is that monkeys received different doses of hormones during the month to mimic the natural hormonal fluctuations of their previous menstrual cycles. Postmenopausal women, who take hormones, usually take a constant dose of estrogen and progesterone.

"The monkeys did not have the same cognitive benefits when they took the same dose every day," says Hara, who now works at the Alzheimer's Drug Discovery Foundation. "This could have implications on the best way to treat postmenopausal women in the future."

Focus on zebrafish

Given the genetic similarities between primates and humans, it is not surprising that they are in great demand by scientists. In 2017, they represented a record 76,000 animals in US research. At the same time, the modest two-inch striped zebrafish, which share 70% of its genes in humans, is also gaining popularity.

"I'm not sure the world knows that these fish are great genetic models for humans. I tell people we are walking fish, "said environmental biologist Keith Tierney of the University of Alberta in Canada. Although their lifespan is only three years, they become adults in three months and allow scientists to quickly see the effects of various interventions.

Zebrafish also experience the same type of muscle loss in the elderly as humans. Tierney begins a study that feeds various zebrafish diets (a vegetarian blend, a mixture of animal muscle proteins and another food with this new source of fashionable protein: crickets) to determine its impact on their athletic performance and their muscle tone as they age. "We put them in zebrafish special treadmills to see how fast they move and how much oxygen they use," Tierney says. "The goal is to learn how to keep our aging human population healthy with cheaper green proteins that are easier to use. [the] environment."

The limits of this science

Despite the wisdom that animals can offer humans, some experts recommend not to overdo it, especially as many promising clinical drug trials in animals fail in humans.

"If we study the DNA of aging in a mouse, it will not give us a predictive value of what happens in humans," says Ray Greek, anesthesiologist near Santa Barbara, California, and co-author of "Animal Models in Light of Evolution. "" There are too many differences between the species that have been adjusted during the course of evolution. We must stop using animals to directly study humans. "

Other experts, such as John Ioannidis, an epidemiologist at Stanford, argue that animal studies are needed to test the safety and effectiveness of interventions before trying them on humans. "The information we can get from animals before going to humans is invaluable," he says.

Yet there are too many variables, including the complexity of diseases and types of animals, to determine which studies will be useful. A review of the medical journal BMJ documented interventions on animals that had an opposite effect on humans. For example, a stroke drug helps animals, but worsens the disease in humans.

For researcher Julie Mattison of the National Institute on Aging, animals will not give us all the answers about how the human is aging, but they could steer scientists in the right direction.. Mattison, who is studying the impact of intermittent fasting on health and longevity, is designing a trial on rhesus monkeys to determine if eating fewer hours for several days will improve brain function, immunity, and metabolism..

"Human studies are often more expensive and complicated because you do not have the same control and monitoring," she says. In other words, the monkeys do not live in a world of processed foods, invitations to great happiness and truffle fries.

"The animal model gives us an opportunity to understand the mechanisms that explain why we could have these benefits," says Mattison. "It's easy to tell people to reduce their calories for a few days. But they need to understand what is happening in their bodies and why such a nutritional intervention could delay aging-related diseases and help them live longer in good health. "

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