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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
Use of nematodes to study evolutionary biology
Nematodes have been used as model organisms for evolutionary studies. This article highlights the key findings from research on developmental processes, sex determination, dauer formation, vulva development, male tail formation and developmental regulation of gene expression with regards to evolution. An updated phylogenetic tree of the phylum Nematoda is also provided. This article is an excellent read to summarise evolutionary differences within nematodes for the above mentioned processes.
Haag, E. S., Fitch, D. H. A., & Delattre, M. (2018). From “the Worm” to “the Worms” and Back Again: The Evolutionary Developmental Biology of Nematodes. Genetics, 210(2), 397 LP – 433. https://doi.org/10.1534/genetics.118.300243
Transgenerational Fitness is a great consideration
Dietary restriction (DR),and various forms of it, have been reported in several models including humans to have health benefits. These studies are usually done within a single generation of animals. However, we sometimes lack foresight and do not consider how our current actions can affect the next generation.
The recent article by Ivimey-Cook shows how a DR model can have detrimental effects on our progeny. The effect of temporary fasting (TF) was investigated on progeny starting from the F1 stage until the F3 stage. TF in Parental, F1 and F2 caused increased lifespan but this lifespan extension due to TF was eliminated in the F3 progeny as their fitness was impacted.
The authors also show how the odour of food causes parental individuals exposed to TF increase their reproduction in exchange for a reduction in their lifespan extension. This food sensing ability of the animals suggest that information is being passed to the offspring to prepare them for their future environment (bad or good). This suggests how the health or current state of parental animals affects their offspring. Therefore, transgenerational effects, which are very relevant now, should be considered heavily for future generations both good and bad.
Ivimey-Cook, E. R. et al. (2021). Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans. Proc. R. Soc. B Biol. Sci. 288, rspb.2021.0701.
High-throughput behavioural screen in C. elegans reveals Parkinson’s disease drug candidates
Recent advances in neural networks (NN) and machine learning (ML) algorithms have been beneficial in expediting labour-intensive nematode research. In this paper, the authors assessing nematode behaviour, use a high throughput screen called C. elegans Snapshot Analysis Platform (CeSnAP) which enables researchers to go beyond subjective scoring and obtain a more reliable data analysis.
The authors discovered a novel link between branched-chain amino acid transferase 1 (BCAT1) and Parkinson’s Disease (PD) as the RNAi knockdown of neuronal bcat-1 in C. elegans causes abnormal age dependant spasm-like ‘curling’ behaviour. Using CeSnAP, the authors performed high-throughput curling analysis of a total of 17,000 worms in order to identify drugs that ameliorate PD-like motor dysfunction. They found that enasidenib, ethosuximide, metformin, and nitisinone are promising candidates for PD.
This study is an example of the increasing trend towards employing neural networks and machine learning in nematode research and how beneficial it can be to effeciently collect and analyze large amounts of data.
Sohrabi, S., Mor, D. E., Kaletsky, R., Keyes, W., & Murphy, C. T. (2021). High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates. Communications biology, 4(1), 1-9.
Old friends to keep old age away
A lot of people these days suffer from allergic and autoimmune diseases, but this appears to be far more prevalent in wealthy countries. The cause, according to the ‘hygiene hypothesis’ is that people’s immune systems are not primed well enough from a young age. They are too clean! Time to get back in touch with some ‘old friends’, i.e., parasites, say Zhang and Gems, in their review titled: ‘Gross ways to live long: Parasitic worms as an anti-inflammaging therapy?’, published in eLife last February.
The authors have reviewed the literature on the potential benefits of exposing people to parasitic helminths. The central idea that they put forth goes as follows: Humans and parasites evolved in a traditional Red Queen interaction, where parasites harm humans, and humans evolved to fight back by way of the immune system. The parasitic worm then in turn evolved to dampen the immune reaction of its host, allowing it to stay without being bothered. This does not exactly benefit the host, but the twist is: dampening the immune system could also inhibit chronic and aging-associated inflammation, a.k.a inflammaging. Hence, the authors propose that a treatment with either live worms, or potentially a cocktail of worm proteins, could be administered as a treatment for allergic and autoimmune inflammatory disorders, as well as inflammaging in order to extend healthspan.
Cheers to that!
– Wouter van den Berg
Zhang B, Gems D. 2021. Gross ways to live long: Parasitic worms as an anti-inflammaging therapy? Elife. 10:1–12. doi:10.7554/eLife.65180.