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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

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

Reference

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.