The activation of protein homeostasis protective mechanisms perhaps is not responsible for lifespan extension caused by deficiencies of mitochondrial proteins in C. elegans

Mitochondrial responsibility in ageing process: innocent, suspect or guilty

“…Thus, inhibition of the mitochondrial superoxide dismutase form, sod-2, in clk-1 mutants results in lifespan extension besides the increase in oxidative damage whereas inhibition of the cytosolic form, sod-1, led to an increase in the life span of daf-2 mutants although, in this case, accompanied by lower oxidative damage (Yang et al 2007). In addition, deletion of these sod genes in wild type worms does not produce decrease in lifespan although increase in oxidative damage was found (Yang et al 2007;Bennett et al 2014;Cabreiro et al 2011;Labunskyy et al 2014;Ren et al 2015;Schulz and Haynes 2015). These results imply that extension of longevity does not necessarily have to correlate with reduced ROS level in C. elegans.…”

“…Interestingly, the effect of overexpression of sod-1 on longevity seems to depend on the activation of the endoplasmic reticulum unfolded protein response (UPR) and not by reduction of oxidative stress that was even higher. The role of the induction of UPR in longevity is currently under controversy since some authors indicate that induction of mitochondrial UPR (mtUPR) is associated with stabilization of mitochondrial function and increase of longevity (Schulz and Haynes 2015), whereas others indicate that mtUPR signal is nor involved in aging in animals including C. elegans (Bennett et al 2014;Ren et al 2015). However, some authors have reported that the endoplasmic reticulumdependent UPR is associated with life span extension (Labunskyy et al 2014).…”

Transaldolase inhibition impairs mitochondrial respiration and induces a starvation-like longevity response in Caenorhabditis elegans

“…Loss of either ATFS-1 or GCN-2 does not prevent the lifespan extension from mitochondrial inhibition [15, 16]. These factors act in a compensatory fashion, however, and GCN-2 may be able to establish mitochondrial protein homeostasis in the absence of ATFS-1 or vice versa.…”

“…Whether the UPR mt plays a direct role in determining longevity remains unclear. Lifespan extension by ETC inhibition or treatment with the ROS-generating compound paraquat is correlated with induction of the UPR mt [7, 10, 14]; however, deletion or RNAi knockdown of atfs-1 blocks induction of several UPR mt target genes but does not prevent or attenuate lifespan extension following inhibition of the ETC [15, 16]. Similarly, constitutive active alleles of atfs-1 cause activation of the UPR mt but do not extend lifespan [15–17].…”

Reconciling the clk-1 and aging paradox and categorizing lifespan curves by taking individual specificity into account

“…Clk-1 was one of the first genes found to be correlated with aging and was widely used to explore aging and neurodegenerative disease related mechanisms (Gu et al, 2017;Lakowski and Hekimi 1996;Larsen and Clarke 2002). However, RNAi knocking down of clk-1 shortened lifespan, although growth rate was not slowed down (Ren et al, 2015;Zhang et al, 2017). In mice, deletion of clk-1 was lethal and its decreased expression promoted neuroinflammation and subsequent death of dopaminergic cells (Gu et al, 2017;Nakai et al, 2001).…”