Assessing metabolic activity in aging Caenorhabditis elegans: concepts and controversies. Answering the ultimate question “what is the proximal cause of aging? Aging (Albany, NY) 2012 4:861–877.īraeckman BP, Houthoofd K, Vanfleteren JR. Life span and stress resistance of Caenorhabditis elegans are differentially affected by glutathione transferases metabolizing 4-hydroxynon-2-enal. 2002 295:502–505.Īyyadevara S, Dandapat A, Singh SP, Siegel ER, Shmookler Reis RJ, Zimniak L, Zimniak P. Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Source data are available in Table S4.Īrantes-Oliveira N, Apfeld J, Dillin A, Kenyon C. (I) Linear regression of the decline in red Dendra2 fluorescence after photoconversion in reference versus daf-2 strains (F-test, p < 0.0001). Right: detail of the midsection of the body. Left: overview of Dendra2-expressing worms. (D) Confocal images of jrIs5 transgenic worms expressing Dendra2 under the constitutive rps-0 promotor and targeted to the mitochondria with the mitochondrial localization signal of gas-1. Asterisks indicate significant differences between both strains. p Values were obtained from the moderated t test implemented in the limma R package and adjusted for multiple testing according to Benjamini and Hochberg's method. Each tile represents a biological replicate. Color limits signify the 5 th (41 hr) and the 95 th (291 hr) percentile. The colors indicate a relative decrease (red) or increase (blue) of protein half-life compared with the median of the reference strain (white, 103 hr). (A–C, E–H, and J–M) Heatmap representation of individual protein half-lives of daf-2 and reference replicates. (15)N-metabolic labeling Caenorhabditis elegans FOXO/DAF-16 aging daf-2 mutant protein turnover.Ĭopyright © 2016 The Author(s). The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory. In contrast, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. This slowdown was most prominent for translation-related and mitochondrial proteins. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry. However, lowering translational efficiency extends rather than shortens the lifespan in C. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death.

Single site mutant protein turnover