NAD supplementation prevents STING-induced senescence in ataxia telangiectasia by improving mitophagy.

Senescence phenotypes and mitochondrial dysfunction are implicated in aging and in premature aging diseases, including ataxia telangiectasia (A-T). Loss of mitochondrial function can drive age-related decline in the brain, but little is known about whether improving mitochondrial homeostasis alleviates senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence-associated secretory phenotype (SASP) occur in A-T patient fibroblasts, and in ATM-deficient cells and mice.

Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations.

Background: The details of the folding mechanisms have not yet been fully understood for many proteins, and it is believed that the information on the folding mechanism of a protein is encoded in its amino acid sequence. β-trefoil proteins are known to have the same 3D scaffold, namely, a three-fold symmetric scaffold, despite the proteins' low sequence identity among superfamilies. In this study, we extract an initial folding unit from the amino acid sequences of irregular β-trefoil proteins by constructing an average distance map (ADM) and utilizing inter-residue average distance statistics to determine the relative contact frequencies for residue pairs in terms of F values.

Cockayne syndrome group A and B proteins function in rRNA transcription through nucleolin regulation.

Cockayne Syndrome (CS) is a rare neurodegenerative disease characterized by short stature, accelerated aging and short lifespan. Mutations in two human genes, ERCC8/CSA and ERCC6/CSB, are causative for CS and their protein products, CSA and CSB, while structurally unrelated, play roles in DNA repair and other aspects of DNA metabolism in human cells. Many clinical and molecular features of CS remain poorly understood, and it was observed that CSA and CSB regulate transcription of ribosomal DNA (rDNA) genes and ribosome biogenesis.

Short-term NAD supplementation prevents hearing loss in mouse models of Cockayne syndrome.

Age-related hearing loss (ARHL) is one of the most common disorders affecting elderly individuals. There is an urgent need for effective preventive measures for ARHL because none are currently available. Cockayne syndrome (CS) is a premature aging disease that presents with progressive hearing loss at a young age, but is otherwise similar to ARHL.