Maria Branyas Morera was 117 when she died in August 2024 — but aspects of her biology looked much younger, new research finds.
The study could help reveal key factors that help some individuals ward off disease and survive to extremely old ages, scientists say.
Before her death in a nursing home in Catalonia, Spain, Branyas held the record for the world’s oldest living person for about a year and a half. Now, a study of urine, blood, stool and saliva samples collected from Branyas in the last year of her life reveals she had a number of factors that potentially protected her against disease. These include genes associated with immune function, fantastic cholesterol levels, and a high level of inflammation-fighting bacteria in her gut.
The study was posted Feb. 25 to the preprint server bioRxiv and has not yet been peer-reviewed.
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“One of the goals of the study was to see and find an explanation for this separation between extreme longevity and being very old, but at the same time not having the diseases of the old,” study lead author Manel Esteller, a cancer epigeneticist at the Josep Carreras Institute in Spain, told Live Science.
Notably, however, not all researchers are convinced that studying supercentenarians — people ages 110 or older — is a fruitful method of understanding longevity. That’s partly because the actual ages of these individuals have been called into question.
The biology of longevity
According to the Guinness Book of World Records, one entity that validates old-age records, Branyas was born in San Francisco in 1907 and lived in Texas and Louisiana before moving to Spain in 1915 with her Spanish-born parents. Other than hearing loss and mobility issues, she remained healthy and cognitively sharp until death.
Esteller and his colleagues investigated Branyas’ genes, immune cells, blood levels of lipids, and proteins in her tissues, comparing her results to those of younger individuals who had undergone similar testing. For example, they compared Branyas’ genetic results to those of 75 other Iberian women in the 1000 Genomes Project, an effort to map variation in the human genome.
This comparison revealed seven rare genetic variants in Branyas’ genome that had never been detected in European populations.
These variants, or distinct versions of genes, were related to cognitive function, immune function, lung function, heart disease, cancer and autoimmune disorders. They may have protected against these diseases and improved organ function, the scientists suggested.
They also found that Branyas had excellent mitochondrial function, meaning the powerhouses that provide cells energy worked better than those of younger women. She also had healthy cholesterol levels and a high production of proteins that are beneficial for immune function.
And based on her stool samples, her gut microbiome was distinct from that of 61- to 91-year olds previously studied. In particular, she showed a high level of actinobacteria, which typically decline in old age. Bacteria of the genus Bifidobacterium, which are known to excrete anti-inflammatory compounds, were especially prevalent. This contrasts the “typical decline of this bacterial genus in older individuals,” the study authors noted.
“She had this bacteria in the gut that protected against inflammation and she had this bacteria for two reasons,” Esteller theorized. “The genome was very welcoming of the population, but [it was] also due to her food.” Branyas reported eating three yogurts a day, he said; fermented foods like yogurt contain probiotics, or living microorganisms that can replenish and maintain the gut microbiome.
A molecular clock
Another intriguing finding was a schism between the molecular markers of aging in Branyas’ body and her chronological age.
When people age, structures at the ends of their chromosomes, called telomeres, become progressively shorter. Telomeres help prevent DNA from fraying, which would contribute to cellular aging and cancer.
As expected for someone of an extreme age, Branyas’ telomeres were almost nonexistent, Esteller said. She also had a large population of a particular type of immune cell, which is typical in older people.
In these two ways, Branyas’ biology looked very old — but another marker of aging on her DNA looked strangely young, the team found.
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As a person ages, DNA accumulates a bunch of molecular tags on its surface, called methyl groups. The methylation of DNA can act like a “clock,” showing how physiologically aged a person is. Branyas’ clock looked like that of someone between age 100 and 110, about a decade younger than she was at death.
In that respect, “her cells still feel like they were centenarian cells,” Esteller said.
What does the study tell us about aging?
An accumulation of many little genetic benefits and lifestyle choices may enable extreme longevity, Esteller concluded. Given the study’s findings, “maybe we can think about interventions now,” he said, including potential drugs to increase life span.
But there may be a caveat to this research and other studies like it: the ages of the subjects it focuses on.
The validation of extreme old age is controversial. For example, in 1997, the oldest person to have ever lived, Jeanne Calment of France, died, and her age was validated by longevity organizations and the Guinness Book of World Records at 122 years old. But critics have since cast doubt on the veracity of that claim, suggesting Calment actually died in 1934 at the age 59.
They contend that her daughter, Yvonne, took on her identity to evade taxes — and in doing so, she inadvertently became the purported oldest person ever. (If these critics are right, the woman who died in 1997 was actually only 99.)
Another study, which is currently under peer review, argues that the problems with old-age validation go far beyond Calment. This research, first released as a preprint in 2019, suggests that regions with the highest reported proportions of extremely old residents are disproportionately poor and unhealthy.
“It doesn’t make sense that this level of poverty would predict good health at any age,” said Saul Newman, a scholar at the Oxford Institution of Population Aging and co-author of that research.
What does predict high numbers of very old people, Newman found, is poor record-keeping. For example, U.S. states established birth certificate systems at different times, and the number of people ages 110 and older drops by an estimated 69% to 82% after that record-keeping improves.
Often, people born before such documentation was de rigueur might not even know their true ages, Newman told Live Science. In poor regions, people might also have been motivated to tack years onto their age or take on the identity of a deceased relative to receive a pension.
In Branyas’ case, she was born a little less than two years after statewide birth certificates came to California in July 1905. Esteller and colleagues relied on the work of age-verification organizations to validate Branyas’ age and did not have direct access to her documents.
When asked, a representative for the Guinness Book of World records provided Live Science with general information on the organization’s methods.
“For age-related record titles, the guidelines include requests for government issued documents and further proof to substantiate the claim,” the representative wrote in an email to Live Science. “Exact information on these guidelines is only available to applicants and/ or legal representation of them.”
The hazy nature of old-age records makes interpreting research on the oldest of the old difficult, Newman said. That Branyas’ epigenetic clock suggests she was between 100 and 110 could indeed suggest that she was a 117-year-old who aged unusually slowly — or it could suggest that her paperwork was wrong, and she was between 100 and 110 when she died, he said.
“How do you distinguish between those two cases?” he said. “That’s the central problem. You don’t know.”
On the other hand, Branyas did undeniably reach old age in enviable health, even surviving a bout of COVID-19 in 2020. Thus, her biology might still help researchers distinguish between changes associated with healthy aging and changes associated with disease.
“For the first time you have biomarkers that can tell you your age, but other biomarkers that can tell you your pathology,” Esteller said. “And these are two different things.”
