Protein Biosynthesis

Publication Title: 
Advances in Experimental Medicine and Biology

Growth and somatic maintenance are thought to be antagonistic piciotropic traits, but the molecular basis for this tradeoff is poorly understood. Here it is proposed that changes in protein synthesis mediate the tradeoffs that take place upon genetic and environmental manipulation in various model systems including yeast, worms, flies and mice. This hypothesis is supported by evidence that inhibition of the TOR (target of rapamycin) pathway and various translation factors that inhibit protein synthesis lead to slowing of growth and development but extend lifespan.

Author(s): 
Kapahi, Pankaj
Publication Title: 
Cell

Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans.

Author(s): 
Denzel, Martin S.
Storm, Nadia J.
Gutschmidt, Aljona
Baddi, Ruth
Hinze, Yvonne
Jarosch, Ernst
Sommer, Thomas
Hoppe, Thorsten
Antebi, Adam
Publication Title: 
Aging Cell

?-adrenoceptors are the common pharmacological targets for the treatment of cardiovascular diseases and asthma. Genetic modifications of ?-adrenergic system in engineered mice affect their lifespan. Here, we tested whether genes encoding for key components of the ?-adrenergic signaling pathway are associated with human longevity. We performed a 10-year follow-up study of the Chinese longitudinal healthy longevity survey. The Han Chinese population in this study consisted of 963 long-lived and 1028 geography-matched young individuals.

Author(s): 
Zhao, Ling
Yang, Fan
Xu, Ke
Cao, Huiqing
Zheng, Gu-Yan
Zhang, Yan
Li, Jianxin
Cui, Hanbin
Chen, Xiaomin
Zhu, Zhiming
He, Hongbo
Mo, Xianming
Kennedy, Brian K.
Suh, Yousin
Zeng, Yi
Tian, Xiao-Li
Publication Title: 
Nucleic Acids Research

The translation of genes encoded in the mitochondrial genome requires specific machinery that functions in the organelle. Among the many mutations linked to human disease that affect mitochondrial translation, several are localized to nuclear genes coding for mitochondrial aminoacyl-transfer RNA synthetases. The molecular significance of these mutations is poorly understood, but it is expected to be similar to that of the mutations affecting mitochondrial transfer RNAs.

Author(s): 
Guitart, Tanit
Picchioni, Daria
PiÒeyro, David
Ribas de Pouplana, LluÌs
Publication Title: 
Cell

Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans.

Author(s): 
Denzel, Martin S.
Storm, Nadia J.
Gutschmidt, Aljona
Baddi, Ruth
Hinze, Yvonne
Jarosch, Ernst
Sommer, Thomas
Hoppe, Thorsten
Antebi, Adam
Publication Title: 
The British Journal of Nutrition

The determination of whether increased dietary protein can positively affect health outcomes is hindered by the absence of prospective, randomized trials directly addressing this issue in which all pertinent variables are controlled. Consequently, we can only address the question deductively by considering the support for the rationale underlying the notion of a beneficial effect of increased dietary protein intake. With regard to health outcomes, we have focused on older individuals.

Author(s): 
Wolfe, Robert R.
Publication Title: 
Cell Metabolism

Iron regulatory proteins (Irps) 1 and 2 posttranscriptionally control the expression of transcripts that contain iron-responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor, and hypoxia-inducible factor 2? (HIF2?). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low-iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2?

Author(s): 
Ghosh, Manik C.
Zhang, De-Liang
Jeong, Suh Young
Kovtunovych, Gennadiy
Ollivierre-Wilson, Hayden
Noguchi, Audrey
Tu, Tiffany
Senecal, Thomas
Robinson, Gabrielle
Crooks, Daniel R.
Tong, Wing-Hang
Ramaswamy, Kavitha
Singh, Anamika
Graham, Brian B.
Tuder, Rubin M.
Yu, Zu-Xi
Eckhaus, Michael
Lee, Jaekwon
Springer, Danielle A.
Rouault, Tracey A.
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Chronic inhibition of the protein synthesis regulator mTORC1 through rapamycin extends life span in mice, with longer extension in females than in males. Whether rapamycin treatment inhibits protein synthesis or whether it does so differently between sexes has not been examined. UM-HET3 mice were fed a control or rapamycin-supplemented (Rap) diet for 12 weeks. Protein synthesis in mixed, cytosolic (cyto), and mitochondrial (mito) fractions and DNA synthesis and mTORC1 signaling were determined in skeletal muscle, heart, and liver.

Author(s): 
Drake, Joshua C.
Peelor, Frederick F.
Biela, Laurie M.
Watkins, Molly K.
Miller, Richard A.
Hamilton, Karyn L.
Miller, Benjamin F.
Publication Title: 
Journal of Molecular Biology
Author(s): 
Air, G. M.
Blackburn, E. H.
Coulson, A. R.
Galibert, F.
Sanger, F.
Sedat, J. W.
Ziff, E. B.
Publication Title: 
Journal of Molecular Biology
Author(s): 
Air, G. M.
Blackburn, E. H.
Coulson, A. R.
Galibert, F.
Sanger, F.
Sedat, J. W.
Ziff, E. B.

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