Azot expression in the Drosophila gut modulates organismal lifespan

Abstract

Cell Competition emerged in Drosophila as an unexpected phenomenon, when confronted clones of fit vs unfit cells genetically induced. During the last decade, it has been shown that this mechanism is physiologically active in Drosophila and higher organisms. In Drosophila , Flower (Fwe) eliminates unfit cells during development, regeneration and disease states. Furthermore, studies suggest that Fwe signaling is required to eliminate accumulated unfit cells during adulthood extending Drosophila lifespan. Indeed, ahuizotl ( azot ) mutants accumulate unfit cells during adulthood and after physical insults in the brain and other epithelial tissues, showing a decrease in organismal lifespan. On the contrary, flies carrying three functional copies of the gene, unfit cell culling seems to be more efficient and show an increase in lifespan. During aging, Azot is required for the elimination of unfit cells, however, the specific organs modulating organismal lifespan by Azot remain unknown. Here we found a potential connection between gut-specific Azot expression and lifespan which may uncover a more widespread organ-specific mechanism modulating organismal survival.

Longitudinal analysis of Flower-dependent cell competition fitness markers inDrosophila melanogaster

“…This observation suggests the cyclic nature of loser cell accumulation and elimination in the absence of azot . It is plausible that, in the absence of Azot, this process of accumulation and elimination may not be optimised, which aligns with the understanding that flies lacking Azot have reduced lifespans (Merino 2023; Merino et al 2013). This observation may indicate the presence of compensatory mechanisms employed by flies to eliminate suboptimal cells when the canonical Flower-dependent cell competition process is compromised, akin to the redundancy of caspases such as Dcp1 and drlCE in certain cellular contexts (Steller 2008; Xu et al 2009), which ensure the seamless execution of apoptosis.…”

“…This depletion of azot correlates with a diminished lifespan and an increased prevalence of degenerative vacuoles (Merino et al 2015). Notably, alterations in azot expression in the gut correlate with corresponding changes in lifespan, reinforcing the pivotal role of Azot and cell competition in the ageing process (Merino,2023).…”

Stemming Tumoral Growth: A Matter of Grotesque Organogenesis

“…The so-called unfit cells were eliminated from the growing organ in the presence of the so-called fit cells [ 69 , 70 ]. Currently, we know that cell competition principles are conserved from Drosophila to humans, playing multiple physiological roles during development, adulthood, disease, and ageing [ 41 , 62 , 63 , 64 , 65 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ].…”