Humans are living longer than ever – but even today, few of us will make it past 100. Even fewer will reach 110, or 115. In fact, in the entire world, there are less than 250 of these “supercentenarians” – aka people older than 110 – and only three of those are 115-plus.
They’re a rare breed, is the point. But why? What sets these super-agers apart from the rest of us? Is it nature, or nurture? A new analysis, not yet peer-reviewed, might turn up some clues – and it’s all thanks to one remarkable woman.
The biology of a super-centennial
Born March 4, 1907, Maria Branyas Morera “was the world’s oldest verified living person from January 17th 2023 until her passing on August 19th, 2024, reaching the age of 117 years and 168 days,” begins the paper. “In Catalonia, the historic nation where [Branyas Morera] lived, the life expectancy for women is 86 years, so she exceeded the average by more than 30 years.”
Where most of us would see an amazing feat of longevity, or perhaps a living connection to a lost past, the researchers behind the paper saw a rare opportunity for data collection.
Using samples collected when Branyas Morera was a sprightly 116 years and 74 days old, the researchers “developed a comprehensive multiomics analysis of her genomic, transcriptomic, metabolomic, proteomic, microbiomic and epigenomic landscapes in different tissues,” the paper reports. From there, they compared the various results against samples from younger subjects, some as young as 25, to see what was different for Branyas Morera.
What they found was striking. Not only were many of the markers associated with age much “younger” than would be expected for Branyas Morera – but in some cases, they were the “youngest” out of all the samples. Take telomere length, for example: the caps at the end of chromosomes are usually seen to decrease in length as we age – but at more than 116 years old, Branyas Morera’s telomeres had the greatest mean length of even subjects in their 30s.
The team found genetic variants known to protect against diseases such as cardiovascular disorders, diabetes, and neurodegeneration – all three of which are some of the leading causes of death in developed nations like the US. And when they used various epigenetic “clocks” to calculate Branyas Moreras’s biological age based on DNA methylation, all of them came back with a result much younger than her full 116 years: “[U]sing six different epigenetic clocks […] all the distinct algorithms of age based on DNA methylation yielded the same result,” the team reported. “Our supercentenarian exhibited a much younger biological age than her real chronological age and this occurred in the three different tissues analyzed.”
That wasn’t true for the control samples – there, as expected, the biological ages roughly lined up with the subjects’ true ages. But when the team double-checked with another, completely unrelated kind of test, they got the same result – suggesting that “one of the reasons that our supercentenarian reached such a world record age was that her cells ‘felt’ or ‘behaved’ as younger cells,” they concluded.
Overall, it’s hard to overstate how unique Branyas Morera’s biology really was – but to really hammer it home: when the team compared her genome to a control set of 75 women from the same area, they found seven rare “extreme” variants that were not present in any other subjects.
“These variants could be unique to her,” the researchers suggested, “and may contribute to her exceptional longevity.”
The lessons of age
On top of Branyas Morera’s incredibly lucky genetic makeup, there were some factors that mixed a dollop of “nurture” into the “nature”. The super-centennial loved yogurt, the team noted, and stuck mostly to a Mediterranean-style diet – fitting, since she lived almost her entire life on the shores of that particular sea. Those habits likely contributed to her extremely healthy gut biome and cholesterol levels – although the researchers did find a lot of genetic variants and a naturally efficient lipid metabolism that likely helped with the latter.
Then there were the gimmes. It may sound cliché, but in some ways it’s true: you’re only as old as you feel – and Branyas Morera seemed to feel pretty young. “In spite of several emotionally painful events during her last years of life, like her son’s death, she kept a strong physical and mental health throughout life with good sleep habits […] and active social life,” the researchers wrote. “She largely enjoyed […] quality time with family and friends, playing with dogs, reading books, growing a garden, walking, and playing the piano.”
All of this activity and healthy living would likely have contributed to her long lifespan – and kept those extra years more enjoyable, too. Staying mentally active can help stave off cognitive impairment and dementia, as can staying social; being physically active, meanwhile, can help you stay independent and physically able for longer. And of course, the two interact with each other: exercise is good for your brain health, and – well, it’s hard to be sad when you’re playing with a pupper.
How to live past 100
So, for those of us hoping to replicate it in a few decades’ time, what was the key to Branyas Morera’s long life? In her own words, it was her “orderly life and pleasant surroundings” – but if you ask the scientists, it was a lot more complicated than that.
“Our findings suggest that extreme human longevity may be characterized by the coexistence of two distinct and potentially unrelated sets of features within the same individual,” they concluded. “On one hand, there are characteristic biomarkers of very advanced age, such as shortened telomeres, clonal hematopoiesis-associated mutations, or an aged B-cell population. On the other hand, there are simultaneously preserved healthy (epi)genetic and functional tissue environment traits.”
“All these findings illustrate how aging and disease can, under certain conditions, become decoupled, challenging the common perception that they are inextricably linked.”
In basic English: Branyas Moreras was very, very lucky, in ways that we probably won’t fully understand for a little while yet. But she made the most of that good fortune, too: she looked after herself right up until the end, eating well, staying active, and hanging out with her friends and family. We should all be so lucky.
The preprint can be read on the bioRxiv server.
