A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA).
InC. 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.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.|Current address: Graduate School of Arts and Sciences, Columbia University, New York, NY 10027, USA.
Thalyana
T
Smith-Vikos
Yale School of Medicine, Department of Internal Medicine, New Haven, CT 06510, USA.
Zuyun
Z
Liu
Bowdoin College, Brunswick, ME 04011, USA.
Christine
C
Parsons
Intramural Research Program, National Institute on Aging, Baltimore, MD 21224, USA.
Myriam
M
Gorospe
Intramural Research Program, National Institute on Aging, Baltimore, MD 21224, USA.
Luigi
L
Ferrucci
Yale School of Medicine, Department of Internal Medicine, New Haven, CT 06510, USA.
Thomas M
TM
Gill
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.|Institute for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Frank J
FJ
Slack
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D017173:Caenorhabditis elegans; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D015854:Up-Regulation
D015415:Biomarkers; D035683:MicroRNAs
aging; biomarker; long-lived; longitudinal study; miRNA; short-lived