From January 2023 to August 2024, María Branyas Morera, who lived in Spain, remained the world’s oldest person, 117 years and 168 days. To understand the biological basis of her extraordinary longevity, researchers analyzed dozens of biological indicators, including the genome, transcriptome, metabolome, proteome, microbiome, and epigenome. The results showed that advanced age and disease are not necessarily interconnected.
Genetics
Researchers analyzed samples of peripheral blood, saliva, urine, and feces collected at different times when the woman was 116 years old.
The results showed no significant chromosomal abnormalities. Her telomeres were very short, with an average length of around 8 kb. Given her good overall health, telomere attrition merely reflected advanced cellular age rather than age-related diseases such as neurodegeneration or diabetes. Interestingly, telomere shortening in supercentenarians may also be linked to the absence of diagnosed cancers, as it can limit the replicative lifespan of malignant cells.
Scientists identified over 91,000 rare genetic variants, seven of which were absent in European populations and may have contributed to exceptional longevity. These variants were related to immune system function, cognitive performance, cardiovascular health, and mitochondrial activity.
Rare variants were particularly enriched in immune response pathways, including T-cell differentiation in the thymus, responses to bacterial and viral infections, antigen receptor signaling, as well as lipid metabolism and neuroprotection pathways. Mitochondrial gene mutations appeared to maintain high mitochondrial activity even in deep old age.
Overall, the analysis showed that longevity is not associated with a single gene or mechanism. Instead, it likely results from the combined effect of rare variants across multiple systems – immune, cardiovascular, neural, and mitochondrial – that together enabled an extraordinarily long and healthy life.
Clonal Hematopoiesis
Blood analysis revealed age-related clonal hematopoiesis (CHIP) involving mutations in the SF3B1 and TET2 genes, which are commonly seen in elderly individuals and associated with higher risks of cancer and cardiovascular disease. However, the woman had never developed such conditions, due to limited clonal expansion or enhanced immune surveillance.
Immune Profile
Single-cell RNA sequencing (scRNA-seq) analysis revealed a high number of age-associated B cells (ABCs). This subpopulation tends to accumulate with age and contributes to a pro-inflammatory environment linked to autoimmunity and infection responses. In ABCs, high activity of the MYC gene indicated cell proliferation and potential pre-malignant transformation. These cells also showed upregulation of pathways related to mitochondrial function, apoptosis regulation, and major histocompatibility complex (MHC) activity.
At the same time, she maintained a high proportion of cytotoxic and memory T cells – a common feature of supercentenarians. The gene expression profile of autophagy-related pathways resembled that of younger individuals, suggesting the preservation of “youthful” cellular traits. Gene activity also indicated ongoing regulation of immune and anti-inflammatory responses.
Lipid Metabolism and Metabolome
The woman displayed exceptionally low levels of VLDL cholesterol and triglycerides, while her HDL (“good”) cholesterol was remarkably high. Her lipid metabolism was highly efficient, and inflammatory markers GlycA and GlycB were minimal – consistent with low systemic inflammation and excellent cardiovascular health. Only a few parameters—low levels of amino acids such as glycine, histidine, valine, and leucine, along with elevated lactate and creatinine—reflected her advanced age.
Proteome of Extracellular Vesicles
Her plasma protein composition differed from that of a control group of younger postmenopausal women. She had higher levels of proteins associated with immune defence, antioxidant protection, fatty acid transport, lipoprotein clearance, and regulation. Levels of SAA1 protein, associated with Alzheimer’s disease, were also elevated; however, she showed no signs of neurodegeneration. The activity of immunoglobulin G genes (IGHG2 and IGHG4) suggested preserved immune memory responses despite aging.
Microbiome and Epigenome
The gut microbiome plays a crucial role in shaping not only metabolism but also inflammation, intestinal permeability, cognitive function, and musculoskeletal health.
DNA analysis of fecal bacteria showed that María Branyas Morera’s microbial diversity was much higher than that of a control group aged 60–90 who had not received antibiotics. Her microbiome was particularly enriched in Actinobacteria, mainly Bifidobacterium – a genus of beneficial bacteria that usually decreases with age but is elevated in centenarians. These microbes reduce inflammation and promote the synthesis of short-chain fatty acids and conjugated linoleic acid – biomarkers of a healthy lipid profile, likely related to her daily consumption of yogurt containing Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus, which supports the growth of bifidobacteria. She also had lower levels of pro-inflammatory Clostridium species, which may have helped prevent age-related inflammatory disorders.
Epigenetic profiling revealed DNA methylation patterns consistent with a younger biological age. Researchers identified 69 genomic regions that differed from those of the control group, mostly showing reduced methylation in genes associated with vascular, skeletal, and metabolic functions. Meanwhile, repetitive DNA elements – which typically lose methylation with age – remained stable, resembling the profile of younger individuals.
María Branyas Morera’s biological age was estimated to be about 23 years younger than her actual age. Her cells “felt” and functioned as if they belonged to a much younger person.
Conclusion
Longevity is a product of both hereditary factors and lifestyle habits. The genome of María Branyas Morera carried rare variants linked to the protection of the heart, brain, immune system, and mitochondria, as well as the absence of harmful mutations – forming a robust genetic foundation for healthy aging.
However, behavioral factors also played a significant role. Her daily yogurt consumption may have supported beneficial bifidobacteria in the gut, reducing inflammation and enhancing metabolism. Similar benefits can arise from calorie-restricted diets, physical activity, and other metabolic interventions that slow the aging process.
Some molecular traits identified in her case point to potential therapeutic avenues for slowing aging. For example, telomere protection may prolong cellular health, while maintaining hypermethylated repetitive DNA regions could preserve genomic stability, suggesting that epigenetic therapies using DNA-demethylating drugs may, in fact, be counterproductive. Conversely, interventions targeting specific layers of epigenetic regulation deserve further exploration.
The example of María Branyas Morera shows that health can persist even in extreme old age. In one individual, markers of aging – such as short telomeres and somatic mutations – can coexist with signs of molecular youth: active lipid metabolism, an anti-inflammatory gut microbiome, and an epigenome associated with chromosomal stability and slower epigenetic aging, confirming that aging and disease are not inseparable.
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Reference
The multiomics blueprint of the individual with the most extreme lifespan
