Cardiovascular resilience in centenarians

Centenarians - individuals aged ≥100 years - provide a unique human model for understanding resilience to cardiovascular ageing. Although cardiovascular and metabolic diseases, including hypertension, heart failure, atrial fibrillation and chronic kidney disease, are common in centenarians, their onset is typically delayed relative to that in individuals aged 80-100 years. Centenarians characteristically have structural changes in the heart and vessels, including concentric left ventricular remodelling, increased myocardial stiffness and vascular ageing, but often without the expected burden of myocardial infarction or overt heart failure. Their cardiometabolic profile is generally favourable, marked by preserved insulin sensitivity in cohorts with a low prevalence of diabetes mellitus, mid-range lipid levels and a low prevalence of obesity. Centenarians also have a distinctive inflammatory and gastrointestinal phenotype, characterized by chronic low-grade inflammation with elevated anti-inflammatory signalling, a gut microbiome that more closely resembles that of younger adults, and preserved intestinal barrier integrity. Genetically and epigenetically, exceptional longevity reflects highly polygenic contributions, selective maintenance of genomic stability and markedly younger epigenetic age compared with chronological age. In this Review, we summarize data on the cardiovascular system among centenarians by framing observations of longevity as a composite of delayed pathology, adaptive compensation and survivorship selection. Understanding the biological, behavioural and environmental mechanisms underlying cardiovascular resilience in extreme longevity might inform strategies to extend cardiovascular healthspan across all ages.