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Senolytic Combination of Dasatinib and Quercetin: Effects on Intestinal Senesces and Gut Microbiota

03/16/2022

Cellular senescence causes age-related disorders like physical dysfunction, disabilities, and mortality caused by tissue inflammation and damage. With aging, senescent cells accumulate in various tissues and at etiological sites of multiple chronic disorders.

Senolytic Combination of Dasatinib and Quercetin: Effects on Intestinal Senesces and Gut Microbiota

The senolytic drug combination, Dasatinib plus Quercetin (D+Q), has been well reported to reduce senescent cell abundance in aged mice. Yet, the effects of long-term D+Q treatment on intestinal senescent cell and inflammatory burden and microbiome composition in aged mice have not been adressed.

In this study, Saccon et al. examined the effect of D+Q on senescence and inflammationmarkers in small  and large intestine in aged mice compared to age-matched placebo-treated mice. They also studied the microbial composition along the intestinal tract in these mice.

They reported then following:

  1. D+Q-treated mice showed significantly lower senescent cell and inflammatory burden in small and large intestine compared with control mice.
  2. They found specific microbial signatures in ileal, cecal, colonic, and fecal regions that are distinctly modulated by D+Q, with modulation being most prominent in small intestine. 
  3. They identified a specific correlation of senescence and inflammation markers with specific microbial signatures.

In summary, the obtained data demonstrated that the senolytic treatment reduces intestinal senescence and inflammation while altering specific microbiota signatures. Thus, optimized senolytic regimens might improve health via reducing intestinal senescence, inflammation, and microbial dysbiosis in older subjects.

The senolytic activity and the effect of polyphenols on ageing will be extensively discussed in Polyphenols Applications 2022.

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