Release date: 2017-11-21
>110 years old
Ms. Goldie Michelson of Massachusetts, USA is the longest-lived American. She died at the age of 113 last year. In the last years of her life, she disclosed her secrets to people who had previously consulted longevity: "walking in the morning, eating chocolate."
“I tried to live the truth,†Mr. Shelby Harris of Illinois often said. He lived to 111 years old, and until the first few months of his death, he also opened the first goal of the local baseball league team in 2012.
Ms. Ill. Emma Morano of Italy lived to 117 years old. A few years before her death, she also made pasta and beat eggs.
Ms. Emma Martina is the longest-lived Italian, living 117 years and 137 days (Source: Wikipedia)
As an extremely rare member of humanity, these supercentenarians who live above 110 years old often attribute longevity to good personal habits.
If lifestyle and luck are one of the main factors that affect people's lives to 90 and 100 years old. But this "really rare longevity", as well as being healthy in the last few months or even years of life, is simply not justified by the "lifestyle".
Compared with humans decades ago, the average life expectancy of modern humans has greatly improved. Living longer, we are welcoming new killers that are harder to beat: cancer, heart disease, stroke, Alzheimer's disease, Parkinson's disease and diabetes. For all of these diseases, aging is the biggest risk factor. An 80-year-old man is 40 times more likely to develop cancer than a middle-aged person, and his risk of developing Alzheimer's disease has increased 600 times.
However, further observations of the super centenarians found that they rarely face long-term disease problems when they are alive!
Until the end of their lives, they rarely suffer from major diseases associated with old age, which keeps their organ function balanced. According to statistics, more than 10% of the super centenarians have no serious aging disease in the last 3 months of life, and this proportion is only 3% among the centenarians.
Then, the super centenarians are more likely to be spared from a variety of aging diseases. Where is the secret?
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Longevity password
In laboratories around the world, scientists are working tirelessly on longevity studies. Fortunately, experiments conducted in animals have shown signs of prolonging life.
Last year, Calico, a California-based company that is working on the genome of naked moles, is 10 times more active than its other close relatives of rodents! Another group of scientists funded by the US government is testing monkeys for a drug that doubles the lifespan of nematodes.
The lifespan of nematodes is generally only 2-3 weeks, and the naked mole can live to 30 years old. However, the current life expectancy in developed countries is close to 80 years.
Therefore, whether the effects observed in these short-lived organisms can be directly transformed into humans is still a small question mark. To study the means of longevity that can be used in humans, it may still be necessary to return to humans for experimentation. So the scientists set their sights on the long-lived old people.
Some scientists suggest that these oldest people may have a genetic advantage and inherit fewer common genetic mutations—those that increase the risk of heart disease, Alzheimer's disease, and other senile diseases.
However, some scholars believe that the super centenarians do not win the probability of random mutations in the genes that cause disease, but they carry the long-lived genetic code in their genomes.
The road to finding a longevity password is full of challenges. One of the challenges is to get the genetic information of the old birthday star.
Search the world
According to statistics, the proportion of super centenarians in humans is one in 5 million, and the proportion in centenarians is one in 1,000. According to this ratio, there are about 1,000 people in the world.
Due to the extremely low proportion, these super centenarians are scattered in every corner of the world. And in many places, it is almost impossible to completely determine the information of a super centenarian because of a vague or missing birth record.
Ms. Jeanne Calment is the longest-lived human being ever, living 122 years and 164 days (Source: Wikipedia)
Even the world's few longevity research groups specializing in "super centenarians", The New England Centenarian Study, also plagued by sample collection, had to lower the age threshold for DNA donors. By the age of 103, although Dr. Thomas Perls, the director of the study, said, "This age (for research) is too young."
The protagonist of this article, Mr. James Clement, has done this "impossible task" by himself. He is a 61-year-old self-proclaimed citizen scientist. In the past six years, he has visited 14 states in the United States and 7 countries around the world to collect blood, skin or saliva samples from super centenarians.
In the past few years, he has been familiar with the list of super-hundred-year-olds who can get them, and created their "109th birthday", "110th birthday" and "111th birthday" as their Google calendar reminder.
Mr. Clement is already very experienced in this, for example, the best time to get a DNA sample is morning. Because it is close to noon, the old people are more willing to eat. After lunch, they may be groggy or snoring. Many old people are still clear-headed. For example, 108-year-old Londoner Dorothy Peel will read the informed consent form with her reading glasses and ask a lot about Mr. Clement's purpose.
Mr. Clement explained that he volunteered to do this, in large part because he had long-lasting and strong interest in longevity, and he also practiced himself. As a superhumanist, he ate low-sugar vegetables and nuts and walked seven miles a day. He understood longevity as "a love for life and health" rather than aversion to death. He has a real belief that a longer life will make humanity more human.
Even with a strong belief and persistent enthusiasm, it is not easy to collect these samples. Mr. Clement said that the sudden cancellation of DNA donations has occurred. Once the 100-year-old milestone is reached, the probability of death in the second year rises to 50%. After the age of 110, this probability is close to 66%. “Even if the car is ready to go, the old man may get sick and can't go.†Mr. Clement also thought of a theoretically feasible way to get to the funeral parlour and extract DNA samples from the remains. But for understandable reasons, he said that family members often refuse to communicate with him at the moment of the death of the old man.
In addition, because the Super Centenarians are almost all women, in order to improve the gender balance of the sample, Mr. Clement had to reduce the target age from 110 to 106.
In 2011, Mr. Clement encountered a setback in collecting samples in Europe. He ordered a cheap kit that can be collected by a finger and stored on a card, a method commonly used by geneticists. After spending a few months, he collected 15 samples through the tool, including Mr. Ralph Tarrant, the oldest person in London. At the age of 108, he still completed the London Times crossword every afternoon.
Later, Mr. Clement's financial conditions improved, and he was able to find a doctor to complete the blood sampling before discovering that the original 15 samples were defective. The gene sequencing laboratory gave him an email feedback saying, "We can't detect any DNA." It’s really a crash to hear this.
Mr. Clement acknowledged the news to him in Professor Church's office. The Harvard professor, a well-known geneticist and co-author of Mr. Celemnt, asked him: "You didn't test these cards?"
Fortunately, that trip to Europe left 23 good samples for Mr. Clement.
Gene Sequencing
Recently, Mr. Clement collected a set of genetic samples from 36 super-hundred-year-olds from North America, the Caribbean and Europe to a non-profit organization called Betterhumans. Harvard University geneticist George Church is the scientific advisor to the organization. He is responsible for arranging the genome sequencing of these samples, and the results will be published by the organization, and the data will be used by any scientist in the world.
With the help of Professor Church, Mr. Clement quickly discovered that there were 2,500 variations between the DNA of the super centenarian and the control group. However, even with the help of graduate students at Church Lab, it is difficult to determine which mutations play an important role in longevity from such a small sample size.
According to Professor Church, super centenarians may have extreme mutations that are unlikely to be detected using standard sequencing techniques that detect only known DNA mutations.
To find genetic mutations that have not yet been discovered, it is necessary to sequence the 6 billion genetic letters of all super centenarians, which is a more expensive process. When Mr. Clement and Professor Church first discussed the idea in 2010, the cost of personal genome sequencing was about $50,000.
After years of technological advancement, the price of individual whole genome sequencing has dropped to about $15,000.
And last spring, Professor Church co-founded a company called Veritas Genetics, announcing that the human genome would be sequenced at $1,000 per person. Professor Church told Mr. Clement that Veritas will sequence the remaining samples.
Professor Church said: "I pay tribute to someone who is willing to take the time to obtain these valuable samples."
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To understand the phenotypic effects of which genetic changes, the number of statistics required typically reaches tens of thousands of DNA samples. Some researchers hope that despite the limited number of existing elderly sample genomes, it is still possible to identify the secrets of super centenarians by studying the genetics of rare diseases. No one knows how much genomic information is required for the study.
Therefore, in the next few years, Mr. Clement will continue to collect more samples without any return. If conditions permit, he hopes to add another dozen samples of American super centenarians.
Keep breathing
In 2016, Mr. Clement visited Mr. Matthews, who was born in 1906 and was the oldest man in the United States. Like most super centenarians, he has a good sense of humour and insight and still enjoys life. His life advice is "keep breathing." At the meeting, he donated his DNA sample to Mr. Clement.
This summer, Mr. Matthews died at the age of 114. A few weeks later, his DNA was sequenced and uploaded to the database by Mr. Clement last month. Like all normal human genome sequences, the beginning of his first chromosome is written like this:
TAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCT
His remaining genetic information, together with the genes of other super centenarians, will be handed over to scientists for interpretation. Whether it contains the secrets of a long, healthy, happy life, remains to be interpreted by Professor Church and other biologists.
If we can find unusual patterns in their 3 billion pairs of A, C, G, and T (bases of four synthetic gene sequences) - can prove to be prolonging their life and maintaining health, we It is conceivable that a drug or gene therapy is designed to replicate this function for use in other humans.
Reference material
[1] The Secret to Long Life? It May Lurk in the DNA of the Oldest Among Us
[2] Google's Long, Strange Life-Span Trip
[3] Wikipedia
Source: WuXi PharmaTech (Wei Signal WuXiAppTecChina)
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