Abstract
Recent evidence supports a role for microRNAs (miRNAs) in regulating the life span of model organisms. However, little is known about how these small RNAs contribute to human aging. Here, we profiled the expression of over 800 miRNAs in peripheral blood mononuclear cells from young and old individuals by real-time RT-PCR analysis. This genome-wide assessment of miRNA expression revealed that the majority of miRNAs studied decreased in abundance with age. We identified nine miRNAs (miR-103, miR-107, miR-128, miR-130a, miR-155, miR-24, miR-221, miR-496, miR-1538) that were significantly lower in older individuals. Among them, five have been implicated in cancer pathogenesis. Predicted targets of several of these miRNAs, including PI3 kinase (PI3K), c-Kit and H2AX, were found to be elevated with advancing age, supporting a possible role for them in the aging process. Furthermore, we found that decreasing the levels of miR-221 was sufficient to cause a corresponding increase in the expression of the predicted target, PI3K. Taken together, these findings demonstrate that changes in miRNA expression occur with human aging and suggest that miRNAs and their predicted targets have the potential to be diagnostic indicators of age or age-related diseases.
Highlights
Human aging is a highly complex process that is characterized by an increase in age-associated diseases such as cancer, type 2 diabetes mellitus, autoimmunity, infections, cerebrovascular and cardiovascular disease
To examine whether miRNA expression is altered with age in a human population, we obtained peripheral blood mononuclear cells (PBMCs) from young (30 year old) individuals and old (64 year old) individuals
We found that most miRNAs are downregulated in older participants compared to younger participants, which is consistent with microarray data from both C. elegans and senescent cells in vitro (Fig. 1)[10,16]
Summary
Human aging is a highly complex process that is characterized by an increase in age-associated diseases such as cancer, type 2 diabetes mellitus, autoimmunity, infections, cerebrovascular and cardiovascular disease. Studies in model systems suggest that longevity can be modulated by changes in gene and protein expression. MiRNAs are small non-coding (,22 nt) RNAs that incorporate into the miRNA-induced silencing complex (RISC) [3]. Recent evidence suggests that microRNAs (miRNAs) are key regulators of gene expression. This complex typically negatively regulates gene expression through mRNA degradation, translation inhibition or by performing both functions [4,5]. Accumulating data suggest that miRNAs are important regulators of a variety of cellular processes including cell proliferation, survival, differentiation and replicative sensescence [6,7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
