A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA).
In C. elegans, miRNAs are genetic biomarkers of aging. Similarly, multiple miRNAs are differentially expressed between younger and older persons, suggesting that miRNA-regulated biological mechanisms affecting aging are evolutionarily conserved. Previous human studies have not considered participants' lifespans, a key factor in identifying biomarkers of aging. Using PCR arrays, we measured miRNA levels from serum samples obtained longitudinally at ages 50, 55, and 60 from 16 non-Hispanic males who had documented lifespans from 58 to 92. Numerous miRNAs showed significant changes in expression levels. At age 50, 24 miRNAs were significantly upregulated, and 73 were significantly downregulated in the long-lived subgroup (76-92 years) as compared with the short-lived subgroup (58-75 years). In long-lived participants, the most upregulated was miR-373-5p, while the most downregulated was miR-15b-5p. Longitudinally, significant Pearson correlations were observed between lifespan and expression of nine miRNAs (p value<0.05). Six of these nine miRNAs (miR-211-5p, 374a-5p, 340-3p, 376c-3p, 5095, 1225-3p) were also significantly up- or downregulated when comparing long-lived and short-lived participants. Twenty-four validated targets of these miRNAs encoded aging-associated proteins, including PARP1, IGF1R, and IGF2R. We propose that the expression profiles of the six miRNAs (miR-211-5p, 374a-5p, 340-3p, 376c-3p, 5095, and 1225-3p) may be useful biomarkers of aging.
['Smith-Vikos|Thalyana|T|', 'Liu|Zuyun|Z|', 'Parsons|Christine|C|', 'Gorospe|Myriam|M|', 'Ferrucci|Luigi|L|', 'Gill|Thomas M|TM|', 'Slack|Frank J|FJ|']
D000368:Aged D000369:Aged, 80 and over D000375:Aging D000818:Animals D015415:Biomarkers D017173:Caenorhabditis elegans D015536:Down-Regulation D020869:Gene Expression Profiling D006801:Humans D008136:Longevity D008137:Longitudinal Studies D008297:Male D035683:MicroRNAs D008875:Middle Aged D010865:Pilot Projects D016133:Polymerase Chain Reaction D015854:Up-Regulation
miRNA longitudinal study aging biomarker long-lived short-lived