MicroRNA Predictors of Longevity in Caenorhabditis elegans

Neither genetic nor environmental factors fully account for variability in individual longevity: genetically identical invertebrates in homogenous environments often experience no less variability in lifespan than outbred human populations. Such variability is often assumed to result from stochasticity in damage accumulation over time; however, the identification of early-life gene expression states that predict future longevity would suggest that lifespan is least in part epigenetically determined. Such “biomarkers of aging,” genetic or otherwise, nevertheless remain rare. In this work, we sought early-life differences in organismal robustness in unperturbed individuals and examined the utility of microRNAs, known regulators of lifespan, development, and robustness, as aging biomarkers. We quantitatively examined Caenorhabditis elegans reared individually in a novel apparatus and observed throughout their lives. Early-to-mid–adulthood measures of homeostatic ability jointly predict 62% of longevity variability. Though correlated, markers of growth/muscle maintenance and of metabolic by-products (“age pigments”) report independently on lifespan, suggesting that graceful aging is not a single process. We further identified three microRNAs in which early-adulthood expression patterns individually predict up to 47% of lifespan differences. Though expression of each increases throughout this time, mir-71 and mir-246 correlate with lifespan, while mir-239 anti-correlates. Two of these three microRNA “biomarkers of aging” act upstream in insulin/IGF-1–like signaling (IIS) and other known longevity pathways, thus we infer that these microRNAs not only report on but also likely determine longevity. Thus, fluctuations in early-life IIS, due to variation in these microRNAs and from other causes, may determine individual lifespan

A New Narnavirus that Infects the Late Blight Pathogen, Phytophthora infestans, with a Supergroup 2 RNA-dependent RNA Polymerase

Phytophthora infestans (Mont.) de Bary is the oomycete that caused the historic Irish potato famine of 1845-1850 and beyond, and it continues to cause worldwide devastation of the modern potato and tomato industries. Double-stranded RNAs (dsRNAs) have been discovered in P. infestans but have never been further investigated. Our lab has discovered several dsRNAs that are effectively viral genomes. One of these viruses has been characterized and is tentatively named Phytophthora infestans RNA virus 4 (PiRV-4). PiRV-4 has a 3.00 kb genome with one open reading frame (ORF) coding for a supergroup 2 RNA-dependent RNA polymerase (RdRp). Based on sequence and phylogenetic comparisons, PiRV-4 is most similar to a linear 20S RNA (2.5 kb) narnavirus found in Saccharomyces cerevisiae. No virus sequence was found in the P. infestans genome. PiRV-4 could not be cured from the P. infestans host after three generations of growth on antiviral media; it is still not clear if the virus is affecting the pathogenicity of its host. PiRV-4 is designated as a new member of the genus Narnavirus in the family Narnaviridae