Monday, December 5, 2022

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    A basement full of worms illuminates the enigma of human aging | Science | The USA Print

    An underground room in Barcelona houses 35 office scanners stored in refrigerated chambers, a few meters from the now sunny Barceloneta beach. American biologist Nicholas Stroustrup He has the key to the door of this strange place, invaded by the roar of a very powerful air conditioner. “This is the longevity machine!” shouts Stroustrup, to prevail over the noise. The scientist, born 39 years ago in Meyersville, carefully opens the lid of one of the scanning devices. It is full of hundreds of worms. Under another cover hundreds more appear. In the room, he calculates, there are more than 20,000 worms. The youngest do not stop moving: they restlessly explore their environment, unknown to them. It is easy to feel dizzy when looking through the microscope at the oldest, already motionless and wrinkled, waiting for death. This unusual machine, claims Stroustrup, could reveal the secrets of aging human beings.

    The scientist launches a surprising reflection: “A person can die at 60 years old, while his identical twin brother reaches 90. There is a lot of randomness in aging, which has nothing to do with genetics.” His worms, he explains, are not that different from humans. They are tiny animals, barely a millimeter long, with a ridiculous and exact number of cells: 959, neither one more nor one less, apart from the ovules and the spermatozoa. A person is made up of about 30 million million cells. However, despite their small size, these worms have everything: a mouth, an anus, a nervous system with 302 neuronsskin, genes, muscles.

    The biologist compares aging to “the game of roulette” and tries to reveal its enigmatic rules. His longevity machine scans the worms every hour, from birth to death. They usually live about 18 days, but scientists do all kinds of experiments to see what happens: they change their diet, stress them, give them drugs, modify their genes, expose them to pathogens, raise or lower the temperature. Stroustrup remembers. He has worked with “millions” of worms, but he remembers some that lived 50 days, as if a person reached 225 years. Why did those worms live so long and their identical siblings didn’t? It is not known.

    Biologist Nicholas Stroustrup shows a microscope image of his worms, at the Center for Genomic Regulation, in Barcelona.
    Biologist Nicholas Stroustrup shows a microscope image of his worms, at the Center for Genomic Regulation, in Barcelona.Christopher Castro

    Stroustrup came up with the idea for the longevity machine when he was a 22-year-old doctoral student. at Harvard University. Since he didn’t have money for fancy automated microscopes, he went to a store and bought an ordinary office scanner. When he first scanned a worm, he was stunned at the resolution. With a ridiculous investment, he could study tens of thousands of animals at a time.

    Its first results were published in 2016 in the magazine Nature, showcase of the best world science. They were surprising data. A multitude of groups of identical worms lived more or less in each experiment, but they always maintained a pattern: within the same group, some lived longer than others. There was a constant randomness in the aging process. Stroustrup’s team has now gone further, investigating another factor besides longevity: how long the worms maintain vigorous movement. “You can see it in your grandparents. As people get older, they don’t move as much anymore. In fact, a person usually spends 10% of his life in a wheelchair. And this also happens in mice and worms. It seems that the loss of mobility is a universal result of aging”, says the biologist.

    The intuitive idea is that animals, including humans, have a biological age, different or not from their real age. A person may be 70 years old based on his date of birth, but his cells could be closer to 55. Stroustrup’s experiment suggests something quite different. Worms that maintain vigorous movement longer—a reflection of healthy living—also live longer. However, the statistical differences indicate that they are two independent variables. The study of him, published this Thursday in the specialized magazine PLOS Computational Biology, states that worms have “at least two biological ages”: one that determines the end of vigorous movement and another that marks the moment of death. Stroustrup intuits that, in reality, there is “a constellation of biological ages”, depending on how one part of the body is viewed or another.

    Can the longevity of a worm really reveal the keys to human aging? Stroustrup sarcastically answers another question: “Can aging research in humans themselves reveal the secrets of human aging?” Repeating his experiments on people, he argues, would take decades. Or even centuries. The current focus is to look for other variables that are strongly correlated with aging, such as the so-called epigenetic clock, chemical marks on DNA that are used to measure biological age. If a drug administered to a person causes an effect on this epigenetic clock, it could be assumed that there will also be an effect on aging, but it would take decades to confirm this. Stroustrup’s new study suggests it’s not that simple. If there are many biological ages, one of these indicators may suggest greater youth, while another denotes old age. Many companies already sell these controversial tests to measure biological age.

    Laboratory plates with the worms 'C.  elegans', in the longevity machine of the Center for Genomic Regulation, in Barcelona.
    Laboratory plates with the worms ‘C. elegans’, in the longevity machine of the Center for Genomic Regulation, in Barcelona.Christopher Castro

    The worms used by Stroustrup belong to the species Caenorhabditis elegans, already the protagonist of experiments that have won three Nobel Prizes: two for Medicine (2002 and 2006) and one for Chemistry (2008). The first of these was for Sydney Brenner, the South African biologist who in the 1960s opted to investigate the function of DNA in these worms. “Genetics turns out to be the master science of biology. In fact, it is the only science and all the rest are simply ways of coming to understand what genes do,” Brenner stated in his memoir. In Stroustrup’s lab, the Indian biotechnologist Natasha Osval and the Spanish neuroscientist Andrea del Carmen inactivate genes of worms in the basement of Barcelona. Del Carmen recalls that other laboratories have managed to make their worms live 10 times longer with a single mutation. “Longevity is very malleable,” she stresses.

    the biochemist Carlos Lopez Otin, an aging expert at the University of Oviedo, points out that Stroustrup’s new experiment shows “a negative correlation” between the period of vigorous movement of the worms and the duration of the subsequent period. “That is, animals with a long healthy life would be doubly lucky, living a shorter final functional decline phase,” he notes. “I would like to think that these results would support the debated existence of a maximum biological limit in the life expectancy of the different species and that, in this specific case, not even the healthiest and most vigorous worms would exceed it”, reasons the Spanish researcher.

    López Otín, who has not participated in this study, warns that more research is needed on the molecular mechanisms involved, to confirm that the results in worms can be extrapolated to humans. “It will be then that this article, and freely paraphrasing John Steinbeck [autor de la novela De ratones y hombres]will become a full-fledged true story Of worms and men”, continues López Otín.

    The Italian hematologist Caroline Florian applauds the new work and stresses that aging is a highly complex process. “We don’t all age at the same rate and the cells and tissues in our body may even age at different rates,” explains Florian, of the Bellvitge Biomedical Research Institute, in Hospitalet de Llobregat (Barcelona). “Given the complexity of aging and the difficulties even in precisely defining when a cell, tissue, or organism is old, it’s all too easy to run into confounding factors,” he continues. “Precisely for this reason, this study in worms has really important implications for our current understanding of how biomarkers can predict human aging,” he celebrates.

    Florian encourages the scientific community to persevere and develop innovative experiments that uncover the true mechanisms of aging. “We are already fully aware that aging is a biological process and that it is possible to treat it to extend the duration of life,” he says.

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