Molecules and Cells

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Fig. 3.

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Fig. 3. Combinatorial C. elegans and mammalian studies regarding the conserved aging regulation by dietary restriction, autophagy, mitochondria, and neuronal system. (A) Dietary restriction upregulates age-dependently downregulated mRNA processing and quality control by improving proper alternative splicing coupled with nonsense-mediated mRNA decay (NMD). Dietary restriction also upregulates DCR-1/Dicer and DRSH-1/Drosha, ribonucleases responsible for miRNA processing, thereby improving longevity-associated miRNA processing. Enhanced mRNA processing and quality control, and miRNA processing contribute to longevity and enhanced fitness in C. elegans and mammals. (B) Autophagy activation regulates aging in a context-dependent manner. HLH-30/TFEB and Krüppel-like transcription factor delay aging by enhancing autophagy. In contrast, genetic inhibition of serum/glucocorticoid-regulated kinase 1 (SGK-1/Sgk1) accelerates aging by activating autophagy. (C) Reduced mitochondrial respiration induces mitochondrial unfolded protein response (UPRmt) and promotes longevity through activation of histone deacetylase HDA-1/HDAC, histone lysine demethylase JMJD-3.1/JMJD3, and histone acetyltransferase CBP-1/CBP/p300. Increased levels of NAD+ promote longevity and ameliorate age-associated disease models via enhancing mitophagy and UPRmt. (D) Levels of SPR-3/4/REST positively correlate with lifespan in C. elegans, mice, and humans. SPR-3/4/REST downregulates neural activity and synaptic function to promote longevity. Increased NAD+ and SPR-3/4/REST levels ameliorate the toxicity caused by amyloid β in C. elegans and mice.
Mol. Cells 2021;44:425~432
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