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Predicting the lifespan

Across metazoans, lifespan varies greatly, not only among species but also within the same species. Much effort has been devoted to discovering genetic and abiotic factors associated with longevity in humans, and many lifespan-extending perturbations in model organisms like C. elegans have been discovered. Interestingly enough, homogenous genetically identical C. elegans are equally variable as the outbred human population.

In this recently published article (Kinser et al 2021) from Zachary Pincus lab, authors propose that this mode of inter-individual differences may be due to the change in the expression of key regulatory genes. To address or test this model, they used the expression of 22 miRNA promoter-driven GFP and predicted the future lifespan of animals. Intriguingly, the authors found that almost 50% of these reporters could effectively predict the lifespan of animals till they died. Moreover, 2 of these reporters (miR-47 and miR-243) that are most accurate in predicting lifespan, are involved in gene regulatory processes that do not require DAF-16/FOXO transcription factor.

Finally, they also show that three of these transgenes (miR-240-786, miR-793, and miR-47) that are expressed in different tissues, and show a differential pattern throughout life, provide redundant information about a single lifespan determinant process. This process is most probably a cell non-autonomous one that does not depend on DAF-16.

Kinser, H. E., Mosley, M. C., Plutzer, I. B. and Pincus, Z. (2021) Global, cell non-autonomous gene regulation drives individual lifespan among isogenic C. elegans. eLife; 10:e65026. DOI: https://doi.org/10.7554/eLife.65026

Network analysis in aged C. elegans reveals candidate regulatory genes of ageing

Aging is an inevitable process in most multicellular organism that is regulated by both genetic and environmental factors. Multiple pathways have been discovered using the nematode species Caenorhabditis elegans which were then shown to be conserved in other higher eukaryotes. Simultaneously gene expression profiling using C. elegans during aging, revealed the identification of age-dependent gene expression alterations that characterize the nematode’s ageing process. Following this, multiple studies led to the construction of genetic and molecular networks that includes well-known aging regulators.
In this paper by Aktypi et al (2021), the authors used a novel approach that revealed candidates which were never been linked to ageing before, thus suggesting promising potential targets/ageing regulators. More specifically, they have combined microarray gene expression profiling of the wild type animals during ageing with network analysis of the differentially expressed genes to detect regulatory genes that have importance in C. elegans ageing, an approach that has not been applied before for the detection of ageing regulators.

Reference:
Aktypi, F. et al. (2021) Network analysis in aged C. elegans reveals candidate regulatory genes of ageing. Biogerontology. (https://doi.org/10.1007/s10522-021-09920-3)