Abstract
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.
Highlights
Healthy aging is usually characterized by preserved cognitive and motor functions
A unique group of aging individuals termed centenarians serves as a healthy aging model, outliving the age of 100, with mostly intact cognition and physical health [1,2,3]. Such exceptionally long-lived individuals (ELLI) are the focus of many studies around the world [4,5,6,7,8,9,10,11,12], and this group is being studied in Israel as well
Longer telomere length (TL) has been associated with exceptional longevity [2,26] through several potential mechanisms [27]
Summary
Healthy aging is usually characterized by preserved cognitive and motor functions. A unique group of aging individuals termed centenarians serves as a healthy aging model, outliving the age of 100, with mostly intact cognition and physical health [1,2,3]. The current study utilizes the IMECS cohort (consisting of ELLI, offspring of ELLI, and controls aged 53–87 with no familial exceptional longevity) to compare between the different DNAm clocks and actual phenotypic measures (such as relative telomere length measurements, cognitive performance, and actual age) from the IMECS cohort. We hypothesize that the DNAm age biomarkers and molecular phenotype of ELLI do not differ from those measures in the much younger offspring and control populations These efforts aim to add knowledge on the phenotype of exceptional longevity and perhaps point at potential therapeutic avenues that might aid in cognitive and physical health preservation or even improvement (as suggested by Fahy et al [45])
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