In a landmark multi-omics case study, researchers report that Maria Branyas, who reached 117 years, exhibited a rare young genome profile: epigenetic clocks reading up to ~23 years younger, a bifidobacteria-rich, infant-like gut microbiome, and low systemic inflammation despite very short telomeres [1]. The blueprint, published in Cell Reports Medicine (DOI 10.1016/j.xcm.2025.102368), integrates her genome, epigenome, microbiome, proteome and metabolome into a single extreme-longevity dataset [1]. The Josep Carreras team later released final data highlighting longevity’s “duality,” where youthful and aged biological signals coexist within supercentenarians [4].

Key Takeaways

– Shows epigenetic clocks read 10–23 years younger than chronological age in a 117-year-old, despite extremely short telomeres and immunosenescence markers [1]. – Reveals an infant-like gut microbiota, dominated by bifidobacteria, alongside low systemic inflammation—an unusual anti-inflammatory signature at age 117 [4]. – Demonstrates protective genetic variants linked to neuro- and cardioprotection and strong lipid metabolism, coexisting with aged B-lymphocyte profiles in this 117-year-old [5]. – Indicates cells behaved 10–17 years younger in functional assays while telomeres remained very short, underscoring longevity’s paradoxical biology [2]. – Suggests single-case insights (n=1) could prioritize microbiome, lipid and epigenetic targets for trials, but require larger cohorts for confirmation [5].

Inside the study: a multi-omics look at a young genome

The Cell Reports Medicine analysis delivers a complete multi-omics portrait of an individual with the most extreme documented lifespan, aggregating genetic and physiological readouts into a “blueprint” of healthy aging at 117 [1]. Researchers profiled her DNA variants, epigenetic marks, protein and metabolite signatures, and gut bacterial composition to see which systems aligned with youth and which reflected advanced age [1]. The integrative approach revealed a striking young genome pattern: epigenetic clocks placed her biological age up to ~23 years younger than her chronological age [1].

Independent reporting noted that, depending on the metric, her cells behaved 10–17 years younger than expected, reinforcing that different epigenetic clocks and functional assays converge on a youthful biological signature [2]. The authors caution that these findings arise from one person, yet the multi-layered design—genome to metabolome—helps disentangle which pathways might most influence extreme longevity, from inflammation control to lipid handling [1]. Lead investigator Manel Esteller emphasized that youthful and aged signals can co-occur in the same person, an observation that could refine how scientists model aging trajectories [4].

How a young genome coexists with extreme aging signals

The dataset shows a biological paradox: while epigenetic measures skew “young,” several hallmarks of aging are undeniably present [1]. Telomeres—protective caps at chromosome ends—were reported as very short, a classic sign of cellular aging observed in many supercentenarians [1]. Immune profiling suggested elements of immunosenescence, including an aged B-lymphocyte landscape, yet systemic inflammation markers remained low, an atypical anti-inflammatory balance at 117 [5]. This juxtaposition of frailty signals and resilience factors is what the study team called a “fascinating” duality [4].

Functionally, cell behavior aligned with youth across multiple readouts, with estimates indicating a 10–17-year biological advantage in certain assays, even as telomeres did not mirror this youthful state [2]. These mixed signals underline that aging is not a single-axis process; different subsystems—genomic stability, immune tone, and epigenetic regulation—may age at different speeds within one individual [4]. For supercentenarians, the pattern may be: some damage accumulates, but key protective circuits stay engaged enough to delay disease onset and preserve function [4].

The microbiome and metabolic clues to resilience

The gut microbiome stood out, resembling infant-like compositions rather than those typical of centenarians, with a pronounced enrichment of bifidobacteria [1]. These bacteria are often associated with beneficial metabolic and immune effects, offering a plausible mechanism for the persistently low systemic inflammation seen despite advanced age [1]. Reports confirm this “youthful” microbiota signature, arguing it may contribute to resilience against inflammaging and infections in late life [4]. Such composition at 117 is exceptional and aligns with lower inflammatory biomarker profiles [5].

Metabolic and organelle-level readouts also skewed favorable. The subject displayed strong lipid metabolism, including efficient cholesterol handling and an “exceptional” lipid profile that could be cardioprotective at extreme ages [2]. Complementary findings described functional mitochondria, supporting sustained cellular energy balance, and robust immune recognition capacity—traits often eroded in typical aging [3]. Together, these findings outline a metabolic-immune axis of resilience: efficient lipid processing, competent mitochondria, and an inflammation-sparing microbiome [3]. This trio could be central to deferring age-related disease well past 100 [3].

Genetic variants: protection amid risk

On the genomic layer, researchers identified protective variants consistent with neuro- and cardioprotection, which may have buffered age-related decline in cognition and cardiovascular health [5]. Such variants do not guarantee longevity but can tilt risk profiles toward resilience, especially when downstream systems like lipid metabolism and immune regulation remain favorable [5]. Notably, these protective alleles co-occurred with signs of immune aging, illustrating that longevity is not the absence of risk, but the dominance of compensatory defenses [5].

From a systems point of view, the genome set the stage, but epigenetic regulation, gut ecology, and circulating proteins and metabolites determined how that blueprint was read and enacted over more than a century [1]. This layered interaction could explain why the epigenetic age skewed markedly “young” even when telomere length did not: different biological clocks capture different aspects of aging biology [1]. The result is a mosaic of risk and protection rather than a uniform “slow aging” phenotype [4].

Limits of a single-case blueprint and the path to validation

The authors are explicit: this is a single-subject case study, and its insights should be treated as hypothesis-generating, not definitive [1]. N=1 designs can reveal possibilities—like a youthful microbiome at 117 or a 23-year epigenetic advantage—but they cannot estimate population-level effects or rule out idiosyncrasies [5]. The team calls for larger cohorts of centenarians and supercentenarians, with standardized multi-omics and longitudinal sampling to map causal pathways and intervention targets [5].

Context matters, too. Esteller noted the likely contributions of genetics, lifestyle, and social factors, cautioning against reductionism in parsing longevity [3]. Environment, diet, early-life exposures, and even care patterns in advanced age could influence microbiome composition and inflammatory tone [3]. Replication across different geographies and ancestries will be essential to validate which markers—microbial taxa, lipid metabolites, epigenetic loci—consistently separate healthy super-aging from typical aging [5].

What a young genome means for aging therapies

Despite its limitations, the blueprint suggests several practical directions. First, epigenetic clocks that moved 10–23 years toward youth could serve as responsive endpoints for lifestyle, microbiome, or drug interventions in trials targeting biological age [1]. Second, the infant-like, bifidobacteria-enriched microbiome at 117 supports testing prebiotic, probiotic, or diet strategies to modulate gut ecosystems and blunt inflammaging [4]. Third, the strong lipid metabolism and exceptional lipid profile argue for deeper study into lipid pathways as levers for cardiometabolic resilience in late life [5].

Genetic findings raise the prospect of screening for protective variants that may inform personalized risk reduction, though translation must avoid genetic determinism [5]. Mitochondrial function and immune recognition capacity could be monitored as composite biomarkers of “functional youth,” complementing DNA methylation clocks in geroscience trials [3]. Ultimately, the coexisting “youthful” and “aged” signatures point to combination strategies—simultaneously tamping inflammation, preserving metabolic flexibility, and supporting beneficial gut taxa—to extend healthspan [4].

The bottom line

This singular case does not rewrite the biology of aging, but it sharpens the map—showing where youthful signatures can persist and how they might be reinforced [1]. For clinicians and researchers, the takeaway is pragmatic: target the pathways that stayed young at 117—epigenetics, microbiome, lipid metabolism, mitochondria, and immune recognition—while acknowledging that some aging hallmarks are likely immutable [3]. Scaling this work to larger, diverse cohorts is the next step toward turning a remarkable outlier into actionable science [5].

Sources:

[1] Cell Reports Medicine – The multiomics blueprint of the individual with the most extreme lifespan: https://doi.org/10.1016/j.xcm.2025.102368

[2] The Guardian – Supercentenarian gives scientists insight on secrets of healthy old age: www.theguardian.com/science/2025/sep/24/supercentenarian-gives-scientists-insight-on-secrets-of-healthy-old-age” target=”_blank” rel=”nofollow noopener noreferrer”>https://www.theguardian.com/science/2025/sep/24/supercentenarian-gives-scientists-insight-on-secrets-of-healthy-old-age [3] El País – “Estudiadme, aprended de mí”: desvelados los secretos de la longevidad de María, la anciana catalana que murió con 117 años: https://elpais.com/ciencia/2025-09-24/estudiadme-aprended-de-mi-desvelados-los-secretos-de-la-longevidad-de-maria-la-anciana-catalana-que-murio-con-117-anos.html

[4] MedicalXpress – Supercentenarian’s biology shows the delicate balance of longevity: https://medicalxpress.com/news/2025-09-supercentenarian-biology-delicate-longevity.html [5] Europa Press – El Instituto Josep Carreras analiza el caso de Maria Branyas para describir la longevidad: www.europapress.es/catalunya/noticia-instituto-josep-carreras-analiza-caso-maria-branyas-describir-longevidad-20250924165951.html” target=”_blank” rel=”nofollow noopener noreferrer”>https://www.europapress.es/catalunya/noticia-instituto-josep-carreras-analiza-caso-maria-branyas-describir-longevidad-20250924165951.html

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