The CellAge Database of Genes Associated with Cellular Senescence

The accumulation of lingering senescent cells is a cause of aging, via the inflammatory and other signals secreted by these cells. This is now widely accepted in the research community, and the first senolytic drugs that can selectively clear some of the burden of senescent cells already exist. Unfortunately it is not yet widely appreciated that these first low cost rejuvenation therapies do in fact exist, and are easily obtained and used. Hundreds of millions of people suffer from inflammatory conditions of aging that can likely be effectively treated via even just a single dose of senolytic drugs. Producing more human data for these existing treatments and bringing them to the vast patient population who would benefit should be much more of a priority than it is today.

Given that any new understanding of the biochemistry of senescent cells might lead to a novel basis for therapies that can greatly improve health in old age, there is a great deal of funding these days for efforts to map the biochemistry of the senescent state. These efforts are giving rise to new startup biotech companies, a few every year, and new candidate small molecule senolytics at an accelerated rate. Here, researchers announce a new database of genes associated with cellular senesence, one of a number of scientific initiatives likely to accelerate progress towards a full understanding of the biochemistry of senescent cells.

Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of ageing and has been linked to ageing-related diseases like cancer. Senescent cells have been shown to accumulate in tissues of aged organisms which in turn can lead to chronic inflammation. Many genes have been associated with cell senescence, yet a comprehensive understanding of cell senescence pathways is still lacking. To this end, we created CellAge, a manually curated database of 279 human genes associated with cellular senescence, and performed various integrative and functional analyses.

We observed that genes promoting cell senescence tend to be overexpressed with age in human tissues and are also significantly overrepresented in anti-longevity and tumour-suppressor gene databases. By contrast, genes inhibiting cell senescence overlapped with pro-longevity genes and oncogenes. Furthermore, an evolutionary analysis revealed a strong conservation of senescence-associated genes in mammals, but not in invertebrates.

Using the CellAge genes as seed nodes, we also built protein-protein interaction and co-expression networks. Clusters in the networks were enriched for cell cycle and immunological processes. Network topological parameters also revealed novel potential senescence-associated regulators. We then used siRNAs and observed that of 26 candidates tested, 19 induced markers of senescence. Overall, our work provides a new resource for researchers to study cell senescence and our systems biology analyses provide new insights and novel genes regarding cell senescence.

Link: https://doi.org/10.1101/743781

Comments

Unrelated, but does anyone know when Oisin will start human trials? Also, any news about Revel (glucosepane breaking)?

Posted by: dayvan_cowboy at August 27th, 2019 8:40 AM

@dayvan_cowboy

I would like to have any news on that too

Posted by: Cuberat at August 27th, 2019 11:55 AM

And I wonder how much more the Oisin approach would cost relative to a small molecule approach to get rid of senescent cells. I imagine it's more - but I have no idea to what extent and if it will be even affordable in the beginning...

Posted by: Chris at August 27th, 2019 4:30 PM

@Chris
The costs depend on the scale and R&D much more than the procedure. If the OISIN toxicity is small it might be worth it. At the end it might cost like Lasik. The basic one is a few hundred bucks, so doable for the whole population even in the mid income countries. For the extremely poor that's another question... I guess the cost will file a similar to HIV pattern

Posted by: Cuberat at August 27th, 2019 5:05 PM

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