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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)

let-7 microRNA absent in many Caenorhabditis nematodes

A recent paper by Nelson and Ambros [1] reports that let-7 heterochronic microRNA is absent in Caenorhabditis species of the japonica group. Research in C. elegans has shown that let-7 plays an essential role during larval to adult transition and mutations in let-7 cause lethality. Authors used one species of the japonica group, C. sulstoni, to further investigate microRNA gene regulatory network. The results revealed that the loss of let-7 function in this species is compensated by other let-7 family members, i.e., miR-48, miR- 84, and miR-241.

Considering that let-7 is highly conserved across bilaterians [2], the results presented in this paper are exciting. However, more work is needed to understand the basis of such an evolutionary change and other potential changes in microRNA-mediated processes.

Reference:
1. Nelson C. and Ambros V. (2021). A cohort of Caenorhabditis species lacking the highly conserved let-7 microRNA. G3, 11(3), jkab022. DOI: 10.1093/g3journal/jkab022.

2. Pasquinelli A.E. et al. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. 408:86–89.