Senolytics: further health benefits discovered

Targeting senescent cells enhances adipogenesis and metabolic function in old age has been demonstrated in new research paper here. The researchers used a JAK inhibitor to reduce the negative signalling produced by senescent cells, whilst the results are interesting the better strategy here is to completely remove such cells and thus eliminate the need to manage the negative signallling. It does demonstrate however what would occur should the source of the problem be removed, senescent cells. The researchers also removed senescent cells in progeric mice and noted a similar reduction of circulating activin A as was obtained with JAK inhibiting. This research further supports clearing away senesecent cells has numerous health benefits and we will be testing the first batch of senolytics in lifespan studies in the new year. 

Senolytics is only going to improve and become more capable of targeting a wider range of cells and as new drugs and therapies are discovered our ability to remove such cells will be nearer 100% removal over the modest 40% Dasatanib and Quercetin has so far produced. It is always going to be a better approach to target the underlying damage than trying to calibrate and control the consequences but this research does demonstrate the benefits of senolytics and targeting of senescent cells. 


Senescent cells accumulate in fat with aging. We previously found genetic clearance of senescent cells from progeroid INK-ATTAC mice prevents lipodystrophy. Here we show that primary human senescent fat progenitors secrete activin A and directly inhibit adipogenesis in non-senescent progenitors. Blocking activin A partially restored lipid accumulation and expression of key adipogenic markers in differentiating progenitors exposed to senescent cells. Mouse fat tissue activin A increased with aging. Clearing senescent cells from 18-month-old naturally-aged INK-ATTAC mice reduced circulating activin A, blunted fat loss, and enhanced adipogenic transcription factor expression within 3 weeks. JAK inhibitor suppressed senescent cell activin A production and blunted senescent cell-mediated inhibition of adipogenesis. Eight weeks-treatment with ruxolitinib, an FDA-approved JAK1/2 inhibitor, reduced circulating activin A, preserved fat mass, reduced lipotoxicity, and increased insulin sensitivity in 22-month-old mice. Our study indicates targeting senescent cells or their products may alleviate age-related dysfunction of progenitors, adipose tissue, and metabolism.

© 2015, Xu et al

This paper is a continuation of the groups reserach into senolytics and senescent cells as this previous paper shows here.

We can see how JAK signalling fits into the system the Conboys describe in their review here and the diagram below shows this interaction. We are testing a number of these interventions and potentially combinations could also be applied to lifespan studies. Support the work of the MMTP and we can explore the potential of these combinations and hopefully speed up the arrival of regenerative medicine.

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© 2015 Conboy et al.