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Many, but not all, mitochondrial respiration mutants exhibit extended lifespan [ 8, 9, 104, 152].
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PSI mutants lacking the U1 snRNP-interacting domain (PSIΔAB mutant) exhibit extended but futile mating attempts.
In fact, the smk-1 gene in C. elegans is required for daf-2 mutants to exhibit extended lifespan, as well as resistance to pathogenic, UV, and oxidative stress.
On the other hand, mutant mice exhibiting reduced GH/IGF1/insulin secretions exhibit extended life span (Brown-Borg et al. 1996; Kurosu et al. 2005).
The mutants akt-1 ok525 akt-1 ok525ok393) land akt-2 ok393 akt-2 ok393in necessary for Akt/PKB activity, yet do not exhibit extended lackspan or increased stress resistance, while akt-2(ok393) mostnts subjected tofakthe(RNAi) have only a 19% lifespan extension as well as a weakinaseease in resistance against high temperatures andomainative stress [ 79, 81].
Both of these mutants also exhibited extended lifespan in our CLS assay.
SPACUNK4.16c is a predicted trehalose phosphate synthase, and the budding yeast tsl1 mutant also exhibits extended chronological lifespan because of diminished trehalose synthesis (Kyryakov et al. 2012).
In the present work, site-directed mutagenesis was performed to delete the C-terminal residues of GAD to generate a mutant, designated as GADΔC, which exhibited extended activity toward near-neutral pH compared to the wild type.
Nematode, fruit fly and mouse mutants with reduced IIS signaling exhibit extended lifespan.
As shown in Supplemental Figure S2D, both tor1Δ and sch9Δ mutants exhibit a longer lifespan in comparison with wild-type, with sch9Δ presenting a more pronounced extended CLS than tor1Δ.
Consistent with this observation, jnk-1 mutants have shorter lifespan than wild-type, and C. elegans overexpressing jnk-1 exhibit extended lifespan in a manner independent of IIS but dependent on daf-16 [ 119].
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