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[albedo]

Wow .. that is interesting. Please assess translation fast, I might be the fist in line for a safe vaccine:

 

"Elimination of senescent cells (senolysis) was recently reported to improve normal and pathological changes associated with aging in mice^1,2. However, most senolytic agents inhibit antiapoptotic pathways³, raising the possibility of off-target effects in normal tissues. Identification of alternative senolytic approaches is therefore warranted. Here we identify glycoprotein nonmetastatic melanoma protein B (GPNMB) as a molecular target for senolytic therapy. Analysis of transcriptome data from senescent vascular endothelial cells revealed that GPNMB was a molecule with a transmembrane domain that was enriched in senescent cells (seno-antigen). GPNMB expression was upregulated in vascular endothelial cells and/or leukocytes of patients and mice with atherosclerosis. Genetic ablation of Gpnmb-positive cells attenuated senescence in adipose tissue and improved systemic metabolic abnormalities in mice fed a high-fat diet, and reduced atherosclerotic burden in apolipoprotein E knockout mice on a high-fat diet. We then immunized mice against Gpnmb and found a reduction in Gpnmb-positive cells. Senolytic vaccination also improved normal and pathological phenotypes associated with aging, and extended the male lifespan of progeroid mice. Our results suggest that vaccination targeting seno-antigens could be a potential strategy for new senolytic therapies."

 

Suda, M., Shimizu, I., Katsuumi, G. et al. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. Nat Aging 1, 1117–1126 (2021). https://doi.org/10.1...587-021-00151-2

https://www.nature.c...-00151-2#citeas

 

 

Edited by albedo, 22 December 2022 - 01:49 PM.

[albedo]

Ok ... a more nuanced view on the paper cited in my previous post:

 

"Finally, the results from Suda et al.^[10] add to the ongoing debate as to the full biological implications of senescent cells. Numerous studies have attested to the deleterious effect of senescence cells; however, recent results suggest a more nuanced view. For instance, Grosse et al.^[15] observed that hepatic endothelial cells in mice aged 12 months displayed high p16^Ink4a expression. Rather than improving the phenotype, elimination of these p16^Ink4a expressing cells resulted in liver fibrosis and disease. Indeed, the role of GPNMB itself remains unresolved. Recently published studies demonstrated that in young mice, GPNMB might play a protective role in metabolic disorders, with Gpnmb KO mice apparently showing impaired metabolic parameters and heightened inflammation stemming from macrophage activation^[16,17]. Besides delineating the beneficial or harmful role of GPNMB, how this protein intersects with other markers of senescent cells, such as p16^Ink4a, p19^arf, and p53, remains unresolved. Are all p16^Ink4a-high senescent cells likewise GPNMB-high, and are all GPNMB-high cells truly senescent? Moreover, could GPNMB expression denote a more deleterious subtype of senescent cells, opening the potential for more specific targeting of good versus bad senescent cells? The answers to these questions and others must await additional analysis. What’s clear is that harnessing the immune system represents a new and potentially powerful strategy to clear senescent cells and potentially treat a host of age-related cardiovascular diseases." (blue mine)

 

Lear TB, Finkel T. Senolytic vaccination: a new mandate for cardiovascular health? JCA. Published online 2022.

https://cardiovascul...e/view/4689#B10