Accurate translation is important for longevity

Ke, Zhonghe; Seluanov, Andrei; Gorbunova, Vera

doi:10.18632/aging.101398

Cited by 4 publications

(2 citation statements)

References 7 publications

(8 reference statements)

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“…Moreover, some researchers found a loss of accuracy of the translation process in aging human fibroblasts [64], a result that could not be confirmed in short-living rodent models [65], indicating that this is not a universal aging hallmark. However, the accuracy of the translation process differs between short- and long-living organisms [66], showing that in fact, long-living species like humans rely on a high quality of protein synthesis. Recently, a study identified decoding-defective ribosomes as a pathomechanism in a human dysmorphic syndrome with microcephaly and impaired intelligence [67].…”

Section: Discussionmentioning

confidence: 99%

Nucleolar and Ribosomal Dysfunction—A Common Pathomechanism in Childhood Progerias?

Phan

Khalid

Iben

2019

Cells

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The nucleolus organizes around the sites of transcription by RNA polymerase I (RNA Pol I). rDNA transcription by this enzyme is the key step of ribosome biogenesis and most of the assembly and maturation processes of the ribosome occur co-transcriptionally. Therefore, disturbances in rRNA transcription and processing translate to ribosomal malfunction. Nucleolar malfunction has recently been described in the classical progeria of childhood, Hutchinson–Gilford syndrome (HGPS), which is characterized by severe signs of premature aging, including atherosclerosis, alopecia, and osteoporosis. A deregulated ribosomal biogenesis with enlarged nucleoli is not only characteristic for HGPS patients, but it is also found in the fibroblasts of “normal” aging individuals. Cockayne syndrome (CS) is also characterized by signs of premature aging, including the loss of subcutaneous fat, alopecia, and cataracts. It has been shown that all genes in which a mutation causes CS, are involved in rDNA transcription by RNA Pol I. A disturbed ribosomal biogenesis affects mitochondria and translates into ribosomes with a reduced translational fidelity that causes endoplasmic reticulum (ER) stress and apoptosis. Therefore, it is speculated that disease-causing disturbances in the process of ribosomal biogenesis may be more common than hitherto anticipated.

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Section: Discussionmentioning

confidence: 99%

Nucleolar and Ribosomal Dysfunction—A Common Pathomechanism in Childhood Progerias?

Phan

Khalid

Iben

2019

Cells

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“…Although there is ongoing debate as to how significantly translation fidelity changes with age, cumulative evidence firmly indicates that the accurate synthesis of proteins defines organismal lifespan and is essential for organismal health ( Tavernarakis and Driscoll, 2002 ; Anisimova et al, 2018 ; Ke et al, 2018 ; Francisco et al, 2020 ). Excluding genomic causes, these errors primarily arise due to inaccurate start and stop codon recognition by the ribosome, amino acid mismatch during the aminoacylation of tRNAs by aminoacyl-tRNA synthetases, and inaccurate aminoacyl-tRNA selection by the ribosomes.…”

Section: Protein Synthesismentioning

confidence: 99%

Insights Into the Links Between Proteostasis and Aging From C. elegans

2022

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Protein homeostasis (proteostasis) is maintained by a tightly regulated and interconnected network of biological pathways, preventing the accumulation and aggregation of damaged or misfolded proteins. Thus, the proteostasis network is essential to ensure organism longevity and health, while proteostasis failure contributes to the development of aging and age-related diseases that involve protein aggregation. The model organism Caenorhabditis elegans has proved invaluable for the study of proteostasis in the context of aging, longevity and disease, with a number of pivotal discoveries attributable to the use of this organism. In this review, we discuss prominent findings from C. elegans across the many key aspects of the proteostasis network, within the context of aging and disease. These studies collectively highlight numerous promising therapeutic targets, which may 1 day facilitate the development of interventions to delay aging and prevent age-associated diseases.

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Accurate translation is important for longevity

Cited by 4 publications

References 7 publications

Nucleolar and Ribosomal Dysfunction—A Common Pathomechanism in Childhood Progerias?

Nucleolar and Ribosomal Dysfunction—A Common Pathomechanism in Childhood Progerias?

Insights Into the Links Between Proteostasis and Aging From C. elegans

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