Exceptionally long-lived individuals (ELLI) who are the focus of many healthy longevity studies around the globe are now being studied in Israel. The Israeli Multi-Ethnic Centenarian Study (IMECS) cohort is utilized here for assessment of various DNA methylation clocks. Thorough phenotypic characterization and whole blood samples were obtained from ELLI, offspring of ELLI, and controls aged 53–87 with no familial exceptional longevity. DNA methylation was assessed using Illumina MethylationEPIC Beadchip and applied to DNAm age online tool for age and telomere length predictions. Relative telomere length was assessed using qPCR T/S (Telomere/Single copy gene) ratios. ELLI demonstrated juvenile performance in DNAm age clocks and overall methylation measurement, with preserved cognition and relative telomere length. Our findings suggest a favorable DNA methylation profile in ELLI enabling a slower rate of aging in those individuals in comparison to controls. It is possible that DNA methylation is a key modulator of the rate of aging and thus the ELLI DNAm profile promotes healthy longevity.

Background Exceptional long‐lived individuals (ELLI) are known for their improved health status and independence regardless of life‐style and health behaviors. Yet, little is known about their cognitive function correlates. The aim of the present study was to assess the correlation between social, clinical, behavioral and personality factors and cognitive impairment in a sample of Ashkenazi Jews (AJ) ELLIs. Method The study sample included 401 AJ participants, aged 95 years or older, of the Longevity Genes Project at Einstein, who were residents of the northeastern United States and lived independently in the community. Socio‐demographic, medical history data and life‐style factors were collected via mailed questionnaires, telephone calls, or in‐person visits. Personality was assessed through the Personality Outlook Profile Scale. In the event that participants had difficulty responding to questions in a reliable manner, their children or legal guardian assisted them. Cognitive status was assessed using the Mini Mental State Exam (MMSE) with a score of 24 or lower considered as cognitive impairment. Cross‐sectional associations of medical, social, life‐style and personality characteristics with odds for cognitive impairment were assessed using logistic regression models while adjusting for potential confounders. Result Of the total sample (mean age=97.72.8 years, 84% women), 178 (44%) were cognitively impaired. Following adjustment for age, sex and education, prevalent skin cancer (OR, 95% CI: 0.40, 0.22‐0.74) as well as being conservative religious (OR, 95% CI: 0.18, 0.03‐0.97) and attending temple in Holidays only (OR, 95% CI=0.25, 0.07‐0.88) and weekly (OR, 95% CI: 0.25, 0.06‐0.97) at age ∼70 years were associated with lower odds for cognitive impairment. Conclusion Cognitive impairment correlates in ELLI may differ from those in the general population. Future studies are warranted to explore the role of religious involvement in brain aging. Furthermore, the strong link between a history of skin cancer and cognition in the oldest‐old should be examined.