scholarly journals Endogenous DAF-16 Spatiotemporal Activity Quantitatively Predicts Lifespan Extension Induced by Dietary Restriction

2021 ◽  
Author(s):  
Javier Huayta ◽  
Adriana San-Miguel
Keyword(s):  
Dietary Restriction ◽  
Food Limitation ◽  
Lifespan Extension ◽  
Cell Protection ◽  
C Elegans ◽  
Quantitative Image ◽  
Longevity Gene ◽  
Fluorescent Tagging ◽  
Endogenous Activity ◽  
Lifespan Variability

In many organisms, dietary restriction (DR) leads to lifespan extension through the activation of cell protection and pro-longevity gene expression programs. In the nematode C. elegans, the DAF-16 transcription factor is a key aging regulator that governs the Insulin/IGF-1 signaling pathway and undergoes translocation from the cytoplasm to the nucleus of cells when animals are exposed to food limitation. In this work, we assess the endogenous activity of DAF-16 under various DR regimes by coupling CRISPR/Cas9-enabled fluorescent tagging of DAF-16 with quantitative image analysis and machine learning. Our results indicate that lifelong DAF-16 endogenous activity is a robust predictor of mean lifespan in C. elegans, and it accounts for 78% of the lifespan variability induced by DR. We found that this lifespan-extending mechanism occurs mainly in the intestine and neurons, and that DR drives DAF-16 activity in unexpected locations such as the germline and intestinal nucleoli.

scholarly journals Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans

2020 ◽  
Author(s):  
Edward R. Ivimey-Cook ◽  
Kris Sales ◽  
Hanne Carlsson ◽  
Simone Immler ◽  
Tracey Chapman ◽  
...  
Keyword(s):  
Dietary Restriction ◽  
Mortality Risk ◽  
Future Generations ◽  
Lifespan Extension ◽  
Dietary Interventions ◽  
C Elegans ◽  
Trade Offs ◽  
Wide Range ◽  
Broad Variety

AbstractDietary restriction increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here we investigated the effect of dietary restriction by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in C. elegans. We show that while TF robustly reduces mortality risk and improves late-life reproduction in the parental generation (P0), it has a wide range of both positive and deleterious effects on future generations (F1-F3). Remarkably, great-grandparental exposure to TF in early-life reduces fitness and increases mortality risk of F3 descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of dietary restriction underscoring the need to consider fitness of future generations in pursuit of healthy ageing.

scholarly journals Delayed development and lifespan extension as features of metabolic lifestyle alteration in C. elegans under dietary restriction

2006 ◽  
Vol 209 (20) ◽  
pp. 4129-4139 ◽  
Author(s):  
N. J. Szewczyk ◽  
I. A. Udranszky ◽  
E. Kozak ◽  
J. Sunga ◽  
S. K. Kim ◽  
...  
Keyword(s):  
Dietary Restriction ◽  
Lifespan Extension ◽  
C Elegans ◽  
Delayed Development

scholarly journals Tubular lysosome induction couples animal starvation to healthy aging

2021 ◽  
Author(s):  
Tatiana V Villalobos ◽  
Bhaswati Ghosh ◽  
Sanaa Alam ◽  
Tyler J Butsch ◽  
Brennan M Mercola ◽  
...  
Keyword(s):  
Food Intake ◽  
Old Age ◽  
Dietary Restriction ◽  
Healthy Aging ◽  
Critical Event ◽  
Lifespan Extension ◽  
Nematode Caenorhabditis Elegans ◽  
Mtor Inhibition ◽  
C Elegans ◽  
New Class

Dietary restriction promotes longevity via autophagy activation. However, changes to lysosomes underlying this effect remain unclear. Using the nematode Caenorhabditis elegans, we show that induction of autophagic tubular lysosomes, which occurs upon dietary restriction or mTOR inhibition, is a critical event linking reduced food intake to lifespan extension. We find that starvation induces tubular lysosomes not only in affected individuals but also in well-fed descendants, and the presence of gut tubular lysosomes in well-fed progeny is predictive of enhanced lifespan. Furthermore, we demonstrate that expression of Drosophila SVIP, a tubular-lysosome activator in flies, artificially induces tubular lysosomes in well-fed worms and improves C. elegans health in old age. These findings identify tubular lysosomes as a new class of lysosomes that couples starvation to healthy aging.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

scholarly journals H3K27 modifiers regulate lifespan in C. elegans in a context-dependent manner

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abigail R. R. Guillermo ◽  
Karolina Chocian ◽  
Gavriil Gavriilidis ◽  
Julien Vandamme ◽  
Anna Elisabetta Salcini ◽  
...  
Keyword(s):  
Lifespan Extension ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Animal Cells ◽  
C Elegans ◽  
Specific Effects ◽  
Aberrant Gene Expression ◽  
Lysine Methyltransferase ◽  
Epigenetic Signatures ◽  
Aberrant Gene

Abstract Background Evidence of global heterochromatin decay and aberrant gene expression in models of physiological and premature ageing have long supported the “heterochromatin loss theory of ageing”, which proposes that ageing is aetiologically linked to, and accompanied by, a progressive, generalised loss of repressive epigenetic signatures. However, the remarkable plasticity of chromatin conformation suggests that the re-establishment of such marks could potentially revert the transcriptomic architecture of animal cells to a “younger” state, promoting longevity and healthspan. To expand our understanding of the ageing process and its connection to chromatin biology, we screened an RNAi library of chromatin-associated factors for increased longevity phenotypes. Results We identified the lysine demethylases jmjd-3.2 and utx-1, as well as the lysine methyltransferase mes-2 as regulators of both lifespan and healthspan in C. elegans. Strikingly, we found that both overexpression and loss of function of jmjd-3.2 and utx-1 are all associated with enhanced longevity. Furthermore, we showed that the catalytic activity of UTX-1, but not JMJD-3.2, is critical for lifespan extension in the context of overexpression. In attempting to reconcile the improved longevity associated with both loss and gain of function of utx-1, we investigated the alternative lifespan pathways and tissue specificity of longevity outcomes. We demonstrated that lifespan extension caused by loss of utx-1 function is daf-16 dependent, while overexpression effects are partially independent of daf-16. In addition, lifespan extension was observed when utx-1 was knocked down or overexpressed in neurons and intestine, whereas in the epidermis, only knockdown of utx-1 conferred improved longevity. Conclusions We show that the regulation of longevity by chromatin modifiers can be the result of the interaction between distinct factors, such as the level and tissue of expression. Overall, we suggest that the heterochromatin loss model of ageing may be too simplistic an explanation of organismal ageing when molecular and tissue-specific effects are taken into account.

scholarly journals Pyruvate imbalance mediates metabolic reprogramming and mimics lifespan extension by dietary restriction in Caenorhabditis elegans

Aging Cell ◽  
2010 ◽  
Vol 10 (1) ◽  
pp. 39-54 ◽  
Author(s):  
Laurent Mouchiroud ◽  
Laurent Molin ◽  
Prasad Kasturi ◽  
Mohamed N. Triba ◽  
Marc Emmanuel Dumas ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Dietary Restriction ◽  
Metabolic Reprogramming ◽  
Lifespan Extension

scholarly journals Automated and customizable quantitative image analysis of whole Caenorhabditis elegans germlines

Genetics ◽  
2021 ◽  
Author(s):  
Erik Toraason ◽  
Victoria L Adler ◽  
Nicole A Kurhanewicz ◽  
Acadia DiNardo ◽  
Adam M Saunders ◽  
...  
Keyword(s):  
Image Analysis ◽  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Meiotic Prophase ◽  
Quantitative Image Analysis ◽  
Dna Breaks ◽  
C Elegans ◽  
Quantitative Image ◽  
Cytological Features ◽  
Single Nucleus

Abstract Arranged in a spatial-temporal gradient for germ cell development, the adult germline of Caenorhabditis elegans is an excellent system for understanding the generation, differentiation, function, and maintenance of germ cells. Imaging whole C. elegans germlines along the distal-proximal axis enables powerful cytological analyses of germ cell nuclei as they progress from the pre-meiotic tip through all the stages of meiotic prophase I. To enable high-content image analysis of whole C. elegans gonads, we developed a custom algorithm and pipelines to function with image processing software that enables: (1) quantification of cytological features at single nucleus resolution from immunofluorescence images; and (2) assessment of these individual nuclei based on their position within the germline. We show the capability of our quantitative image analysis approach by analyzing multiple cytological features of meiotic nuclei in whole C. elegans germlines. First, we quantify double-strand DNA breaks (DSBs) per nucleus by analyzing DNA-associated foci of the recombinase RAD-51 at single-nucleus resolution in the context of whole germline progression. Second, we quantify the DSBs that are licensed for crossover repair by analyzing foci of MSH-5 and COSA-1 when they associate with the synaptonemal complex during meiotic prophase progression. Finally, we quantify P-granule composition across the whole germline by analyzing the colocalization of PGL-1 and ZNFX-1 foci. Our image analysis pipeline is an adaptable and useful method for researchers spanning multiple fields using the C. elegans germline as a model system.

scholarly journals Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans

2021 ◽  
Vol 288 (1950) ◽  
Author(s):  
Edward R. Ivimey-Cook ◽  
Kris Sales ◽  
Hanne Carlsson ◽  
Simone Immler ◽  
Tracey Chapman ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Dietary Restriction ◽  
Mortality Risk ◽  
Lifespan Extension ◽  
Dietary Interventions ◽  
Negative Effects ◽  
Trade Offs ◽  
Wide Range ◽  
Broad Variety

Dietary restriction (DR) increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here, we investigated the effect of DR by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in Caenorhabditis elegans . We show that while TF robustly reduces mortality risk and improves late-life reproduction of the individuals subject to TF (P 0 ), it has a wide range of both positive and negative effects on their descendants (F 1 –F 3 ). Remarkably, great-grandparental exposure to TF in early life reduces fitness and increases mortality risk of F 3 descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of DR, underscoring the need to consider fitness of future generations in pursuit of healthy ageing.

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