Longevity Briefs: Longevity Lessons From The (Former) Oldest Living Person

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

In August 2024 we lost Maria Branyas Morera, then the World’s oldest known living person at 117. She lived in the Catalonia region of Spain. Her age qualified her as a supercentenarian – a person who has reached the age of 110. Supercentenarians are exceptionally rare. In 2023, there were only 16,140 100 year-olds living in the UK – that’s fewer than 3 for every 10,000 inhabitants. Statistics suggest that even if you do live to 100, your chances of then living another 10 years are only around 1 in 500.

One might expect people this old to be burdened with many age-related diseases. On the contrary, while centenarians and supercentenarians can’t exactly be described as ‘healthy’, they often have fewer chronic age-related diseases than people several decades younger than them. Are they just lucky? Research does suggest that certain genes granting a predisposition to exceptional longevity are practically required to reach these kinds of ages, but those genes can still teach us a great deal about the biology of ageing. And while genes play a significant role, it is likely that lifestyle practices we can copy also play their part in becoming a supercentenarian. Here, researchers study the particular case of Branyas. It is not often that we get to learn from the biology of someone so old.

The discovery:

Researchers collected samples of blood, saliva, urine and stool from Branyas over multiple visits, allowing them to compare her genetic makeup, gene expression, protein profile, metabolism and gut microbiome to others living in the same region. They found that Branyas did indeed exhibit clear markers of extreme age. She had significantly shortened telomeres – the protective caps at the ends of chromosomes that shorten with each cell division. Once telomeres become too short, the cell can no longer divide. Telomere shortening is thought to be one of the key drivers of ageing, and restoring telomere length in animal models has been shown to delay it. She also exhibited clonal haematopoeisis – that’s the accumulation of a subpopulation of blood cells that are all descended from a single mutated stem cell.

Yet in spite of these traits, she also displayed traits associated with healthy ageing and disease resistance. She had a healthy ratio of high density lipoprotein (HDL) to low density lipoprotein (LDL) – so called ‘good cholesterol’ and ‘bad cholesterol’ respectively. She had low levels of inflammatory markers, suggesting a healthy immune system for her age. In support of this, she was the oldest woman in Spain to survive Covid-19, which she caught when she was 113. She also had a gut microbial community characteristic of a much younger person, possibly influenced by her three daily servings of yogurt. The gut microbiome and the immune system are known to be interlinked, so Branyas’ immune health may have been partly due to her healthy microbiome. Particularly noteworthy was the high relative abundance of Bifidobacterium, a genus with a positive association with digestive and immune health and which is found in some fermented foods.

Last but not least, Branyas was found to posses many gene variants that are associated with exceptional longevity in humans and other species. These included rare variants linked to immune function, preservation of cognitive function in old age, DNA repair and the function of mitochondria (the ‘cellular organs’ that convert nutrients into usable ‘fuel’ for the cell). She also had a distinct lack of any gene variants associated with increased risk of age related diseases. When researchers used epigenetic clocks – algorithms that estimate biological age by measuring molecular alterations to the DNA molecule that accumulate throughout life – they estimated that Branyas had a biological age at least a decade below her actual ‘chronological’ age.

The implications:

Unfortunately, research concerning exceptional human longevity suggests that even with the healthiest lifestyle possible, you are unlikely to live to an exceptional age if you don’t also have good genes. However, studies like this also remind us that being old does not have to mean being sick, and this is something that appears to apply more broadly and is heavily influenced by lifestyle factors. Even if you won’t live to 100, adopting a healthy lifestyle will still significantly delay the onset of age-related diseases or even prevent them entirely, leading to more years lived in good health. Branyas maintained a healthy weight, ate a Mediterranean diet, exercised and socialised regularly, and didn’t smoke or drink. While she needed the genes to get her to 117, these are all healthy practices associated with increased longevity that would benefit any age group.