Main findings: Spalax fibroblasts undergo replicative senescence and etoposide‐induced senescence, evidenced by an increased activity of SA‐β‐Gal, growth arrest, and increased p21, p16, and p53 (Fig. A);
Yet, unlike mouse and human fibroblasts, Spalax senescent cells showed undetectable or decreased expression of the well‐known SASP factors (Fig. B);
High efficiency of DNA repair is responsible to suppression of inflammatory response in Spalax (Fig C);
Downregulation of SASP secretion in Spalax senescent fibroblasts is associated, at list in part with suppression of IL1α cytokine response and inhibition of NF-kB translocation to the nuclei (Figs. D and E); Evaluation of SASP in ageing Spalax tissues confirmed downregulation of inflammatory‐related genes (Fig. F)

Odeh, A., Dronina, M., Domankevich, V., Shams, I ., Manov, I. 2020. Downregulation of the inflammatory network in senescent fibroblasts and aging tissues of the long‐lived and cancer‐resistant subterranean wild rodent, Spalax . Aging Cell, 19(1):e13045

The uncoupling of senescence phenotype and the inflammatory component of SASP (senescent-associated secretory phenotype) was discovered in long‐lived blind mole rat, Spalax, adapted to extreme environments. Cellular senescence in Spalax, evidenced by increased SA‐β‐Gal activity, upregulation of p21/p16/p53, is not accompanied by accumulation of DNA damage nor by secretion of SASP factors. We suggest that genome integrity, inhibition of NF‐κB nuclear translocation, and IL1α suppression are involved in overcoming the inflammatory response in aging Spalax.

We propose that suppression of SASP in senescent Spalax cells, as well as inhibition of inflammation in aging Spalax, can support a nonpermissive microenvironment for cancer progression, as well as the suppression of sterile inflammation, which is the cause of most aging‐related pathologies