Dietary restriction improves proteostasis and increases life span through endoplasmic reticulum hormesis.
Latika Matai,Gautam Chandra Sarkar,Manish Chamoli,Yasir Malik,Shashi Shekhar Kumar,Umanshi Rautela,Nihar Ranjan Jana,Kausik Chakraborty,Arnab Mukhopadhyay +8 more
TL;DR: A transient pharmacological ER stress, imposed early in development on Caenorhabditis elegans, enhances proteostasis, prevents iUPRER decline with age, and increases adult life span and dietary restriction (DR), that has a conserved positive effect on life span, employs this mechanism of ER hormesis for longevity assurance.
read more
Abstract: Unfolded protein response (UPR) of the endoplasmic reticulum (UPRER) helps maintain proteostasis in the cell. The ability to mount an effective UPRER to external stress (iUPRER) decreases with age and is linked to the pathophysiology of multiple age-related disorders. Here, we show that a transient pharmacological ER stress, imposed early in development on Caenorhabditis elegans, enhances proteostasis, prevents iUPRER decline with age, and increases adult life span. Importantly, dietary restriction (DR), that has a conserved positive effect on life span, employs this mechanism of ER hormesis for longevity assurance. We found that only the IRE-1-XBP-1 branch of UPRER is required for the longevity effects, resulting in increased ER-associated degradation (ERAD) gene expression and degradation of ER resident proteins during DR. Further, both ER hormesis and DR protect against polyglutamine aggregation in an IRE-1-dependent manner. We show that the DR-specific FOXA transcription factor PHA-4 transcriptionally regulates the genes required for ER homeostasis and is required for ER preconditioning-induced life span extension. Finally, we show that ER hormesis improves proteostasis and viability in a mammalian cellular model of neurodegenerative disease. Together, our study identifies a mechanism by which DR offers its benefits and opens the possibility of using ER-targeted pharmacological interventions to mimic the prolongevity effects of DR.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
Transcriptomic profiling of long- and short-lived mutant mice implicates mitochondrial metabolism in ageing and shows signatures of normal ageing in progeroid mice.
Matías Fuentealba,Daniel K. Fabian,Handan Melike Dönertaş,Janet M. Thornton,Linda Partridge,Linda Partridge +5 more
TL;DR: In this article, the authors analyzed and compared gene expression data from 10 long-lived and 8 short-lived mouse models of ageing and identified 58 gene sets with consistent changes in long- and shortlived mice.
9
Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications.
TL;DR: A dose-response relationship to stressors, according to the hormesis theory, is characterized by low-dose stimulation and high-dose inhibition as discussed by the authors, which is non-linear with a lowdose optimum.
8
Functionally analyzing the important roles of hepatocyte nuclear factor 3 (FoxA) in tumorigenesis.
TL;DR: This review comprehensively summarize the impressive progression of FoxAs functional annotation, clinical relevance, upstream regulators and downstream effectors, as well as valuable animal models, and highlight the potential strategies to target FoxAs for cancer therapies.
8
Molecular Biomarkers of Health
Jan O. Nehlin,Ove Andersen +1 more
- 01 Jan 2020
TL;DR: This work attempts to provide a glimpse to how a state of good health could be maintained by adhering to the individual reference values of personalized molecular biomarkers of health under periodical clinical supervision.
6
Dietary Restriction And Lifespan: Adaptive Reallocation Or Somatic Sacrifice?
02 Feb 2022
TL;DR: In this article , the authors propose a likely mechanism for this observation, which involves a trade-off between lifespan and reproduction, but in a manner that is conditional on the dietary supply of an essential micronutrient, a sterol.
5
References
The Hallmarks of Aging
TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.
13K
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Peter Walter,David Ron +1 more
TL;DR: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum, where they fold and assemble, and only properly assembled proteins advance from the ER to the cell surface.
Role of the Calcium-Sensing Receptor in Cardiomyocyte Apoptosis via the Sarcoplasmic Reticulum and Mitochondrial Death Pathway in Cardiac Hypertrophy and Heart Failure
Fanghao Lu,Songbin Fu,Xiaoning Leng,Xinying Zhang,Shiyun Dong,Yajun Zhao,Huan Ren,Hulun Li,Xin Zhong,Changqing Xu,Weihua Zhang +10 more
TL;DR: It is demonstrated that CaR activation caused Ca2+ release from the SR into the mitochondria and induced cardiomyocyte apoptosis through the SR and mitochondrial apoptotic pathway in failing hearts.
The mammalian unfolded protein response
TL;DR: In the endoplasmic reticulum (ER), secretory and transmembrane proteins fold into their native conformation and undergo posttranslational modifications important for their activity and structure as mentioned in this paper.
3.1K