Recent studies suggest that the steady rise in life expectancy observed over the past 200 years has now stagnated. Data indicate that a limit has been reached, and that medical and healthcare advances no longer affect longevity in developed countries as they did in previous decades. Today, ageing itself, rather than disease, is the real frontier of human longevity. But what exactly is ageing? And can it be addressed in the same way as a disease?
A team led by Dr Manel Esteller, Head of the Cancer Epigenetics group at the Josep Carreras Leukaemia Research Institute, has just published the final peer-reviewed data from the study of the longest-lived person ever recorded, who far exceeded 117 years: the Catalan woman Maria Branyas. The analysis, based on samples obtained using minimally invasive techniques, takes a multi-omic approach with genomic, proteomic, epigenomic, metabolomic and microbiomic technologies, and represents the most exhaustive study ever undertaken on a supercentenarian.
In the paper, published in the prestigious journal Cell Reports Medicine, the international and multidisciplinary team coordinated by Dr Esteller and led by Eloy Santos explains that individuals who reach supercentenarian age do not do so through a general delay in ageing but, as Esteller notes, thanks to a “fascinating duality: the simultaneous presence of signals of extreme ageing and of healthy longevity.”
Although the team detected unmistakable signs of ageing, such as very short telomeres (the ends of chromosomes), a pro-inflammatory immune system, and an aged population of B lymphocytes, Branyas also had genetic characteristics associated to neuroprotection and cardioprotection, genuinely low inflammatory levels, a microbiome dominated by beneficial bifidobacteria, and a biological age younger than her chronological age, as determined by epigenetic markers.
Since ageing of the blood system is known to be closely linked to a higher incidence of incurable blood cancers such as leukaemia and myelodysplastic syndromes, the insights gained from this supercentenarian study may also provide valuable clues for deepening our understanding of these haematological conditions and of the patients affected by them.
Key Microbiome Findings
Maria’s intestinal ecosystem looked nothing like that of typical older adults. Diversity was higher, with a bacterial community rich in Bifidobacterium—a genus that usually dwindles with age but is prized for its anti-inflammatory properties and ability to support metabolic and immune balance. In fact, elevated Bifidobacterium is a recurring feature among centenarians, and in M116 it was unusually abundant.
Diet appears to have played a role. For more than two decades, she ate three yogurts a day, introducing bacteria such as Streptococcus thermophilus and Lactobacillus delbrueckii—species known to encourage Bifidobacterium growth. This simple dietary habit may have helped her microbiome resist the decline typically seen in later life.
Equally telling was what her gut lacked. Harmful bacteria, including members of Proteobacteria and Clostridium, were conspicuously scarce. Both are associated with inflammation, frailty, and age-related disease. Their absence, combined with her abundance of beneficial microbes, painted a picture of a gut environment primed for resilience.
These microbial signatures align with other markers of health observed, such as low inflammation and favorable lipid metabolism. Together, they suggest that her microbiome acted as a stabilizing force—one that not only supported digestion but also protected her immune system, brain, bones, and muscles well into extreme old age.
While her epigenetic profile confirmed a biologically “younger” age, it is the microbiome that emerges as the most tangible, modifiable piece of her longevity puzzle.
Impact on Science of Ageing
The absence of serious disease makes this the first study in which ageing can be clearly distinguished from illness, offering a comprehensive view of the effects of ageing on the human body and perhaps pointing to ways to counteract them. Although it is still too early to link specific biological characteristics to specific habits, the researchers note that a healthy diet, a stimulating and diverse social network, and the absence of toxic habits are factors worth considering when explaining for Mrs Branyas’s exceptional longevity.
With this detailed perspective on extreme ageing, researchers worldwide will be able to better understand this natural process and to propose strategies to address it specifically, in the same way that a disease would be treated. In fact, epigenetic therapies and drugs specifically designed to combat senescence already exist in the field of oncology, aspects that are directly related to biological ageing. Who knows if, in the future, those same tools will be responsible for pushing life expectancy forward once again, after its current plateau.
This research has received public funding from the Generalitat de Catalunya, the European Community, and the Spanish Ministry of Science, Innovation and Universities, as well as private support from the “la Caixa” Foundation, the Cellex Foundation, the Spanish Association Against Cancer, and the John and Lucille Van Geest Foundation.
Reference Article:
Santos-Pujol et al. “The multiomics blueprint of the individual with the most extreme lifespan”. Cell Reports Medicine (2025), https://doi.org/10.1016/j.xcm.2025.102368
The Josep Carreras Leukaemia Research Institute
Patients with blood cancers are the core and genuine purpose of the Josep Carreras Leukaemia Research Institute’s mission. At IJC, leading researchers and professionals are dedicated to learning, curing, and ultimately eradicating haematological cancers through three key pillars: specialised working groups focused on excellence in research; our translational programme, which aims to bring our latest discoveries to the clinic; and our new Computational Diagnostics Centre, which combines AI-driven approaches with biological expertise to deepen disease understanding and advance therapeutic development.
In addition to being accredited as a Severo Ochoa Centre of Excellence by the Spanish Ministry of Science, Innovation and Universities – State Research Agency, the Josep Carreras Institute is also CERCA, research centres of excellence of the Generalitat de Catalunya, and is accredited by the Scientific Foundation of the Spanish Association Against Cancer.