Secrets of centenarians against Alzheimer’s disease | Sciences

The doorbell rings and hostess Susan Hoosang van Rimsdijk opens the door. She lives in Hilversum, Central Holland, on a ground floor, independent property. It is a Saturday in July, there is a light breeze and the flowers have been planted decorating the entrance. Nothing seems exceptional except for the 102-year-old hostess. In perfect condition, lives alone, swims, bikes and drives short distances, plays bridge, eats a balanced diet and has a close relationship with her two daughters, six grandchildren and 14 great-grandchildren.

Centenarians are a unique demographic for analyzing the genetic underpinnings of longevity as well as risk factors for degenerative disorders, and Susan is among the 332 Dutch of this generation who participated in a study on the relationship between health and cognitive ability in old age. Led by biochemist Hein Holsteg at the University Hospital in Amsterdam, scientists have observed that the genome of this group of centenarians is enriched with protective genetic elements. Although Alzheimer’s-related proteins build up in your brain as you age, they seem to counteract the effects of these risk factors. The research could contribute to improving treatment for dementia patients.

As Holstig, who has been studying centenarians since 2013, explains that if you reach this age, “the probability of developing dementia is greater than the probability of dying, so after a century of life, no one should be healthy from a .cognitive point of view.” She explains that there are people who maintain cognitive health even after the age of 110 – the so-called age of the twentieth century – and wants to know “how it is scientifically possible to complete a century with good cognitive abilities, what are the molecular mechanisms that maintain the mind in the long-term. And what is the role that You play inheritance,” she says over the phone. To this end, since 2013, her team has annually visited members of the study group, with an average age of 100.5 years, to measure attention, cognition, comprehension, and memory. Scientists also request stool samples for bacterial analysis. About 75% of women, and more than half of them live independently in their own homes. The experts also sequenced his genome and compared it to the DNA of people with dementia, in collaboration with the Alzheimer’s Center in Amsterdam. The goal is to track protective genetic variants enriched in healthy centenarians, which distinguish them from the rest of the population.

The genome is one tool for understanding what does not go well in the brain with dementia, Holstig says, “because between 60% and 80% of the likelihood of developing it or developing Alzheimer’s disease, which is the predominant form, is determined by genetics.” He adds: “We see that the centenarians maintained the effectiveness of the immune response (in the study group, some beat cancer and coronavirus), and we look forward to seeing how they resisted the decline of defenses against disease and, in this way, protecting those at risk of mental decline.” About 30% of the study group would agree to donate their brains to science when the time is right.

It was the long life of the Dutch woman, Hendrikje van Andel Schipper, who passed away in 2015 in full clarity, that prompted biochemistry to pay attention to these elderly people. The Netherlands does not appear in the list of the so-called blue zones of the world, where there are people who exceed the average age for their surroundings (including Japan, Greece, Costa Rica, California and Italy), but it has a significant number of centenarians in good shape. In 2020, there were 2,006 women and 392 men aged 100 and over, out of a population of 17 million, according to the Central Bureau of Statistics. By 2029, the same source predicts that there will be around 3,400 centenarians “because of a small baby boom after World War I.”

Susan Hoosang-van Remsdijk was born in 1919, her two daughters are 74 and 70 years old. In the photos decorating her living room, they both look much younger. Her husband, who was an electronics engineer, died at the age of 67. “Very young, unfortunate. He was a smoker,” she says, then recounts a chapter of her youth summarizing her physical strength and the hardships of the Nazi occupation of the country throughout World War II. With her husband hiding “in a gap between the pantry and the kitchen, lest he be taken to Germany for forced labour,” Susan would bring food using a wood-reinforced bicycle and car tire. “It was a lot of weight, but I would travel 145 kilometers in one direction and another in equal measure, looking for food on a farm in the east of the country. Other people did the same, producers did not ask for money or jewelry. Just clothes. The first time I came back dressed Pajamas, which is the only thing I have left,” she recalls. At the start of their marriage, she wasn’t working (“it used to be that way”), but between her fifties and eighties she was a pedicure and beautician. He also devoted himself to Japanese shiatsu massage, receiving the corresponding diplomas.

Another research participant is Fritz Prochus, also 102, who lives in the western town of Zandvoort, famous for its Formula 1 ring. Fritz has been a police investigator for three decades. Graceful and playful, he talks with the reporter while his garden is filled with sparrows. “I usually have breakfast outside, and they’re on my knees waiting for the crumbs,” he says. Frits take care of his eyes and ears, love meat and herring, and drink some wine. He practically did not smoke, he reads the English writer John le Carré in English and listens to classical music. I did a lot of exercise, too. “I played soccer and badminton, hiked and swam, and used the bike a lot,” he explains. He shows off a modern tricycle he uses to visit his 64-year-old daughter, son-in-law and two granddaughters who were close to him. Family photos decorate the room and cheerfully show it. 14 kilometers from the daughter’s house, count back and forth. Two years ago, he could travel up to 80 kilometers. But he also had his fall: at the age of 80, he broke his femur while playing badminton. At 92, a dog knocked him off his bike, and he took two months off with a broken pelvis.

Susan’s mother turned 95 years old. Frits is the seventh out of 10 siblings. Two of his sisters are 102 years old, the third 103, and 98. The remaining two brothers are 98 and 95 years old. Another died at age 52 “due to smoking,” he says. He describes their marriage as “extremely happy,” and is moved to remember that the couple lost a daughter at age 17, to a brain tumor, as well as two children. His memory is from the twentieth century. World War II surprised him when he was 21 years old, when he was already working for the local Dutch police. “It was a very difficult time because you never knew if the Gestapo would show up or not. There was also bombing, and when a plane was brought down, no one came out alive. He remembers it wonderfully.”

Without knowing each other, both centenarians agree that “physical exercise helps to age in better conditions.” According to Holstig, the better the cognitive state, the longer they will live. “And we see that their children benefit from the genetic factor,” says the scientist who suggested learning from them.

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