Study Explains How Genetics And Lifestyle Combined To Keep A 117-year-old Healthy

A groundbreaking study of a 117-year-old female reveals really protective genetics, a balanced microbiome, businesslike metabolism, and resilient immunity activity together to prolong wellness into utmost aged age.

Maria Branyas Morera blowing retired candles connected nan juncture of her 117th day connected March 4, 2024. Arxiu de la família Branyas Morera, Public domain, via Wikimedia Commons

In a recent Cell Reports Medicine diary paper, an world squad of researchers conducted a broad multiomics study of nan world’s oldest surviving personification and compared her information pinch matched cohorts.

They identified factors underpinning her guidance to emblematic age-related conditions: debased inflammation, protective familial variants, a younger epigenome, and a youthful microbiome, thereby pointing toward hypotheses for imaginable strategies and campaigner biomarkers of patient aging.

Background

The taxable of this study, Maria Branyas Morera, was nan world’s oldest verified surviving personification from January 17, 2023, to August 19, 2024, yet reaching nan bonzer property of 117 years and 168 days.

She was calved successful San Francisco successful 1907 to Spanish parents and moved to Spain astatine nan property of eight, wherever she spent nan remainder of her life. Her individual history provided a unsocial opportunity to analyse nan biologic and biology factors that lend to utmost quality longevity.

While nan number of centenarians worldwide is steadily expanding arsenic world life expectancy rises, individuals who unrecorded beyond 110 years and are classified arsenic supercentenarians stay highly rare.

Maria Branyas Morera lived successful Catalonia, wherever nan mean female life expectancy is 86 years, surpassing it by complete 3 decades. Her singular endurance draws attraction to nan cardinal question: what biologic mechanisms sustained her wellness into specified precocious aged age?

In nan aforesaid measurement that premature aging syndromes, specified arsenic Hutchinson-Gilford Progeria and Werner syndrome, person provided valuable insights into accelerated aging processes, studying supercentenarians offers a reverse perspective: clues astir protective mechanisms that licence unusually agelong and patient lifespans.

Investigating specified individuals whitethorn thief disentangle nan narration betwixt aging and disease, revealing pathways that support resilience against age-related decline.

About nan study

To research nan processes that alteration utmost longevity, researchers conducted an extended multiomics study that examined aggregate molecular layers of biology. Most analyses were performed connected humor collected astatine 116 years and 74 days, pinch saliva, urine, and stool providing complementary data. Maria Branyas Morera’s information were systematically compared pinch those from non-supercentenarian populations to place distinguishing features of utmost aging.

A scope of biologic samples, including blood, urine, saliva, and stool, was collected, on pinch elaborate records of her manner and aesculapian history. Peripheral humor mononuclear cells were isolated and preserved for cellular and familial analyses.

Chromosomal building was evaluated utilizing modular karyotyping, while telomere magnitude (a well-established biomarker of aging) was measured pinch precocious imaging techniques.

High-molecular-weight deoxyribonucleic acerb (DNA) extracted from humor cells was subjected to optical genome mapping, and DNA from aggregate tissues underwent whole-genome sequencing.

Detected familial variants were compared pinch those of a Spanish power cohort to place uncommon aliases perchance protective alleles. Further analyses included tests for clonal hematopoiesis, single-cell ribonucleic acerb (RNA) sequencing to qualify immune compartment populations, and proteomic profiling of plasma extracellular vesicles.

Serum samples were analyzed utilizing metabolomics, pinch a attraction connected lipid profiles, amino acids, and glycoproteins, providing penetration into metabolic ratio and cardiovascular health.

The gut microbiome was studied done nan familial sequencing of stool samples and compared pinch publically disposable datasets, providing penetration into microbial contributions to longevity. Together, this multiomics attack produced a highly elaborate image of her genetics, immune function, metabolism, and microbiota.

Key findings

One of nan striking observations was that, contempt having highly short telomeres (~8 kb mean, pinch 40% beneath nan 20th percentile), Maria Branyas Morera remained healthy. This suggests that telomere shortening whitethorn bespeak chronological property without needfully predicting nan onset of illness. The authors hypothesize that utmost telomere attrition whitethorn enactment arsenic a timepiece alternatively than a illness marker and estimate that it could moreover constrain malignant clones.

Genetic study revealed uncommon variants successful genes associated pinch immune strategy function, cardiovascular protection, neurological health, and mitochondrial function. No azygous version explained longevity, and nan canonical FOXO3A longevity allele was absent; instead, aggregate uncommon alleles crossed pathways appeared to lend collectively.

Blood testing uncovered mutations emblematic of clonal hematopoiesis (SF3B1 and TET2), a process often tied to crab and cardiovascular disease. Yet Maria Branyas Morera displayed nary specified conditions. Instead, her immune floor plan was characterized by expanded cytotoxic T cells and age-associated B cells, on pinch circumstantial “young-like” look features successful selected pathways and upregulation of IgG genes, each of which indicated immune resilience contempt her precocious age.

Mitochondrial usability successful her humor cells was robust, arsenic indicated by assays that suggested a preserved power accumulation capacity compared to controls.

Metabolomic studies person demonstrated businesslike lipid metabolism, characterized by debased triglyceride levels, reduced “bad” cholesterol, elevated “good” cholesterol, and decreased markers of inflammation.

These features are associated pinch protection against cardiovascular illness and dementia. Her extracellular vesicles carried proteins that promoted immune defense, lipid transport, and protection against oxidative stress, reinforcing nan image of robust biologic defenses. Notably, nan SAA1 macromolecule was elevated compared to that of younger postmenopausal controls, yet she showed nary signs of neurodegenerative disease.

Analysis of nan gut microbiome revealed unusually precocious levels of Bifidobacterium, a beneficial bacterium typically reduced successful aged individuals, but known for its anti-inflammatory effects and links to patient aging. She consumed astir 3 yogurts daily, each containing Streptococcus thermophilus and Lactobacillus delbrueckii, which tin support Bifidobacterium growth. The authors statement that this dietary nexus is plausible but unproven without longitudinal sampling.

Epigenetic testing revealed unique DNA methylation patterns. Remarkably, her “biological age” was importantly younger than her chronological age, pinch an rDNA methylation property of ~23.17 years younger and a antagonistic property gait of −17.34 years, indicating preserved genomic stableness and a decelerated epigenetic aging process. In addition, she retained hypermethylation of repetitive elements (LINE-1, ALU, ERV) that typically suffer methylation pinch age, perchance contributing to genomic protection.

Conclusions

Overall, Maria Branyas Morera’s bonzer longevity resulted from a convergence of protective familial variants, resilient immune function, businesslike metabolism, robust mitochondrial performance, a favorable gut microbiome, and unchangeable epigenetic regulation, collectively preserving her wellness into utmost aged age.

These traits interacted to sphere wellness into utmost aged age, illustrating that aging and illness can, nether definite circumstances, beryllium decoupled.

A awesome spot of this study is its broad multiomics approach, which provided an unprecedented extent of study crossed aggregate biologic layers. However, arsenic a cross-sectional, blood-centric study of a azygous individual, causal conclusion and wide generalizations stay limited.

Future investigation should analyse larger cohorts of long-lived individuals and trial targeted interventions, specified arsenic dietary changes, exercise, metabolic therapies, and microbiome modulation. It is besides important to statement that immoderate epigenetic interventions whitethorn require be aware owed to nan protective domiciled of repetition hypermethylation.