Mutant Genes That Extend Life Span

1987 ◽  
pp. 91-100
Author(s):  
Thomas E. Johnson ◽  
David B. Friedman ◽  
Paul A. Fitzpatrick ◽  
William L. Conley
Keyword(s):  
Life Span ◽  
Extend Life Span ◽  
Mutant Genes

scholarly journals The genetic paradigms of dietary restriction fail to extend life span in cep-1(gk138) mutant of C. elegans p53 due to possible background mutations

2020 ◽  
Author(s):  
Anita Goyala ◽  
Aiswarya Baruah ◽  
Arnab Mukhopadhyay
Keyword(s):  
Life Span ◽  
Dietary Restriction ◽  
Model Systems ◽  
Regulation Of Expression ◽  
Life Span Extension ◽  
Phenotypic Differences ◽  
C Elegans ◽  
Xenobiotic Detoxification ◽  
Organismal Biology ◽  
Extend Life Span

AbstractDietary restriction (DR) increases life span and improves health in most model systems tested, including non-human primates. In C. elegans, as in other models, DR leads to reprogramming of metabolism, improvements in mitochondrial health, large changes in gene expression, including increase in expression of cytoprotective genes, better proteostasis etc. Understandably, multiple global transcriptional regulators like transcription factors FOXO/DAF-16, FOXA/PHA-4, HSF1/HSF-1 and NRF2/SKN-1 are important for DR longevity. Considering the wide-ranging effects of p53 on organismal biology, we asked whether the C. elegans ortholog, CEP-1 is required for DR-mediated longevity assurance. We employed the widely-used TJ1 strain of cep-1(gk138). We show that cep-1(gk138) suppresses the life span extension of two genetic paradigms of DR, but two non-genetic modes of DR remain unaffected in this strain. We find that in cep-1(gk138), two aspects of DR, increased autophagy and the up-regulation of expression of cytoprotective xenobiotic detoxification program (cXDP) genes are dampened. Importantly, we find that background mutation(s) in the strain may be the actual cause for the phenotypic differences that we observed and cep-1 may not be directly involved in genetic DR-mediated longevity assurance in worms. Identifying these mutation(s) may reveal a novel regulator of longevity required specifically by genetic modes of DR.

scholarly journals Genetic and pharmacological interventions in the aging motor nervous system slow motor aging and extend life span inC. elegans

2019 ◽  
Vol 5 (1) ◽  
pp. eaau5041 ◽  
Author(s):  
Guang Li ◽  
Jianke Gong ◽  
Jie Liu ◽  
Jinzhi Liu ◽  
Huahua Li ◽  
...  
Keyword(s):  
Nervous System ◽  
Life Span ◽  
Motor Neurons ◽  
Neuromuscular Junctions ◽  
Functional Decline ◽  
Bk Channel ◽  
Pharmacological Interventions ◽  
Genetic Ablation ◽  
Extend Life Span ◽  
Age Dependent

As animals and humans age, the motor system undergoes a progressive functional decline, leading to frailty. Age-dependent functional deteriorations at neuromuscular junctions (NMJs) contribute to this motor aging. However, it is unclear whether one can intervene in this process to slow motor aging. TheCaenorhabditis elegansBK channel SLO-1 dampens synaptic transmission at NMJs by repressing synaptic release from motor neurons. Here, we show that genetic ablation of SLO-1 not only reduces the rate of age-dependent motor activity decline to slow motor aging but also surprisingly extends life span. SLO-1 acts in motor neurons to mediate both functions. Genetic knockdown or pharmacological inhibition of SLO-1 in aged, but not young, worms can slow motor aging and prolong longevity. Our results demonstrate that genetic and pharmacological interventions in the aging motor nervous system can promote both health span and life span.

scholarly journals Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila

2016 ◽  
Vol 113 (40) ◽  
pp. 11277-11282 ◽  
Author(s):  
Jason G. Wood ◽  
Brian C. Jones ◽  
Nan Jiang ◽  
Chengyi Chang ◽  
Suzanne Hosier ◽  
...  
Keyword(s):  
Life Span ◽  
Dietary Restriction ◽  
Fat Body ◽  
Transcriptase Inhibitor ◽  
Dna Double Strand Breaks ◽  
Expression Of Genes ◽  
Age Related ◽  
Extend Life Span ◽  
Genetic Interventions ◽  
Heterochromatin Structure

Transposable elements (TEs) are mobile genetic elements, highly enriched in heterochromatin, that constitute a large percentage of the DNA content of eukaryotic genomes. Aging in Drosophila melanogaster is characterized by loss of repressive heterochromatin structure and loss of silencing of reporter genes in constitutive heterochromatin regions. Using next-generation sequencing, we found that transcripts of many genes native to heterochromatic regions and TEs increased with age in fly heads and fat bodies. A dietary restriction regimen, known to extend life span, repressed the age-related increased expression of genes located in heterochromatin, as well as TEs. We also observed a corresponding age-associated increase in TE transposition in fly fat body cells that was delayed by dietary restriction. Furthermore, we found that manipulating genes known to affect heterochromatin structure, including overexpression of Sir2, Su(var)3–9, and Dicer-2, as well as decreased expression of Adar, mitigated age-related increases in expression of TEs. Increasing expression of either Su(var)3–9 or Dicer-2 also led to an increase in life span. Mutation of Dicer-2 led to an increase in DNA double-strand breaks. Treatment with the reverse transcriptase inhibitor 3TC resulted in decreased TE transposition as well as increased life span in TE-sensitized Dicer-2 mutants. Together, these data support the retrotransposon theory of aging, which hypothesizes that epigenetically silenced TEs become deleteriously activated as cellular defense and surveillance mechanisms break down with age. Furthermore, interventions that maintain repressive heterochromatin and preserve TE silencing may prove key to preventing damage caused by TE activation and extending healthy life span.

Sirtuin activators: Designing molecules to extend life span

2010 ◽  
Vol 1799 (10-12) ◽  
pp. 740-749 ◽  
Author(s):  
Antoni Camins ◽  
Francesc X. Sureda ◽  
Felix Junyent ◽  
Ester Verdaguer ◽  
Jaume Folch ◽  
...  
Keyword(s):  
Life Span ◽  
Extend Life Span

scholarly journals Antagonizing Methuselah to extend life span

2007 ◽  
Vol 8 (8) ◽  
pp. 222 ◽  
Author(s):  
Nazif Alic ◽  
Linda Partridge
Keyword(s):  
Life Span ◽  
Extend Life Span

scholarly journals Long-lived Indy and calorie restriction interact to extend life span

2009 ◽  
Vol 106 (23) ◽  
pp. 9262-9267 ◽  
Author(s):  
P.-Y. Wang ◽  
N. Neretti ◽  
R. Whitaker ◽  
S. Hosier ◽  
C. Chang ◽  
...  
Keyword(s):  
Life Span ◽  
Calorie Restriction ◽  
Extend Life Span

scholarly journals UPRER promotes lipophagy independent of chaperones to extend life span

2020 ◽  
Vol 6 (1) ◽  
pp. eaaz1441 ◽  
Author(s):  
Joseph R. Daniele ◽  
Ryo Higuchi-Sanabria ◽  
Jenni Durieux ◽  
Samira Monshietehadi ◽  
Vidhya Ramachandran ◽  
...  
Keyword(s):  
Life Span ◽  
Genetic Factors ◽  
Protein Homeostasis ◽  
Life Span Extension ◽  
Unfolded Protein ◽  
Extend Life Span ◽  
Protein Chaperones ◽  
Ectopic Activation ◽  
The Unfolded Protein Response ◽  
Protein Response

Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms to regulate life-span extension is the induction of protein chaperones for protein homeostasis. Ectopic activation of the unfolded protein response of the endoplasmic reticulum (UPRER) specifically in neurons is sufficient to enhance organismal stress resistance and extend life span. Here, we find that this activation not only promotes chaperones but also facilitates ER restructuring and ER function. This restructuring is concomitant with lipid depletion through lipophagy. Activation of lipophagy is distinct from chaperone induction and is required for the life-span extension found in this paradigm. Last, we find that overexpression of the lipophagy component, ehbp-1, is sufficient to deplete lipids, remodel ER, and promote life span. Therefore, UPR induction in neurons triggers two distinct programs in the periphery: the proteostasis arm through protein chaperones and metabolic changes through lipid depletion mediated by EH domain binding protein 1 (EHBP-1).

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