ArticleGeroScience2025
Multiparametric profiling of plasma cell-free nucleic acids in nonagenarians and centenarians highlights age-related differences associated with longevity.
Article in GeroScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Plasma circulating cell-free nucleic acids (ccfNAs) have emerged as promising non-invasive biomarkers of aging. While age-associated changes have been reported, data in relation to extreme aging and longevity remain scarce. Here, we assessed ccfNA levels and integrity, and ccfDNA methylation in a cohort of 86 individuals, analyzed both overall and stratified by sex, including nonagenarians (NON: 90-98 years, n = 29), centenarians (CEN: 100-109 years, n = 28), and a middle-aged control group (CG: 38-67 years, n = 29) of nonagenarians' and centenarians' offspring, using our previously optimized multiparametric analysis workflow targeting nuclear (ccfnDNA) and mitochondrial (ccfmtDNA) DNA, ribosomal RNA (ccfrRNA), messenger RNA (ccfmRNA), and microRNAs (ccfmiRNAs). ccfnDNA levels followed non-linear trajectories, decreasing from CG to nonagenarians (28%-64.5%, significant in nonagenarian men compared to CG), then slightly increasing in centenarians. ccfmRNA and ccfmtDNA followed the opposite pattern, with significantly lower ccfmRNA levels in centenarians (44.5%), and both were strongly correlated (r = 0.59-0.83, p < 0.0001), suggesting a shared regulatory mechanism. Additionally, ccfnDNA integrity significantly decreased from CG to CEN (20.7%), while ccfmtDNA and ccfrRNA integrities, and ccfDNA methylation, did not vary. Among the seven ccfmiRNAs analyzed, miR-93-5p, miR-126-3p, and liver-specific miR-122-5p, exhibited significant age-related decreases (40.5%-70.3%), reaching their lowest levels in centenarians. Our study thereby provides novel findings regarding age- and sex- related changes in ccfNAs, highlighting both dynamic and stable characteristics linked to longevity. It identified potential ccfNA-based longevity biomarkers, and supports ccfmiRNAs as the most promising and sensitive biomarkers of longevity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.