Exceptionally Long-Lived Individuals (ELLI) Demonstrate Slower Aging Rate Calculated by DNA Methylation Clocks as Possible Modulators for Healthy Longevity

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.

Similar burden of pathogenic coding variants in exceptionally long‐lived individuals and individuals without exceptional longevity

“…Thus, we believe that in ELLI genomes the rate of mutation accumulation slows down, resulting in a similar amount of pathogenic mutations between ELLI and controls. We recently established a younger DNA methylation profile in ELLI in a smaller cohort of ELLI and unrelated controls, demonstrating DNA methylation clocks under‐estimating the phenotypic age of ELLI, supporting the slower rate of the aging process in ELLI (Gutman et al, 2020). This hypothesis requires additional in depth assessment and testing, not presented in our current study.…”

Identification Of A Group For Research Of Telomeric Aging

“…The first assumption is the simplest one -people born with longer telomeres, tend to start training early, and achieve finally high athletic results. Longer telomeres were observed in long-livers aged 100 or more, and their relatives (Gutman et al, 2020). But in these groups of centenarians, professional athletes were practically not present.…”

“…The search for active longevity reveals presence of correlation of telomere length with various physiological and psychological characteristics. Long-livers tend to have longer telomeres, they are creative and demonstrate preservation of basic cognitive functions (Gutman et al, 2020). Connection of longevity with cognitive functions and creativity was shown in quite a few studies (Colombo et al, 2018;Fancourt & Steptoe, 2018;Joung & Lee, 2019).…”

No Time to Age: Uncoupling Aging from Chronological Time

“…Moreover, decelerated DNAm aging is observed in calorie-restricted and long-lived dwarf mice [ 63 , 64 ]. DNAm age deceleration is also seen in extremely long-lived humans who also have extended healthspans [ 76 ]. Thus, DNAm clocks are useful for measuring both accelerated and decelerated aging within a species.…”