| Aging is a universal phenomenon that is experienced by diverse organism. Aging can be defined broadly as progressive decline in cellular functions in an organism with increasing age, decreasing the ability to survive challenges. Understanding and deciphering the mechanisms involved in this process has been a key focus of current science. An important goal of aging research is not only to identify different approaches to maximize human lifespan, but to also improve the quality of life with increasing age. MicroRNAs (miRNAs) are known to regulate a range of biological processes including cell differentiation, cell death, development, oncogenesis, and metabolism, but little is known about how they impact the biology of aging. Our research mainly focuses on identifying how miRNAs, small molecules that target partially homologous transcripts to block their translational expression, influence healthspan and lifespan in C. elegans. We have identified many mir deletion mutants that impact different aspects of aging like longevity, metabolic and muscle aging. There are four measures that reflect how well or how poorly the animals are aging: age pigment levels, swimming body bend frequency assays, pharyngeal pumping rates, and lifespan studies. Applying these tests, we have studied miRNAs mir-1, mir-256 and mir-238 in a focused manner. Importantly, we have also found that the mir-80(Delta) mutant modulates dietary restriction- a metabolic condition in which reduced caloric intake significantly increases lifespan in a wide range of species. mir-80(Delta) mutant exhibits multiple parameters of healthy aging, reduced reproductive phase and expression of molecular reporters associated with dietary restriction. Using RNAi knockdown, we have identified multiple transcription factors (SKN-1, DAF-16 and HSF-1) and a transcriptional co-factor CBP-1 that seems to play an important role in making mir-80(Delta) long-lived through dietary restriction. In short, we have discovered the first ever microRNA (miR-80) that modulates dietary restriction and longevity in C. elegans . In sum, we have shown that microRNAs can modulate various aspects of C. elegans healthspan, and determined the role of some microRNAs in aging, muscle physiology and dietary restriction. Becaue miRNA signaling can be conserved, our studies will provide clues to similar processes in vertebrates, including humans. |
