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.

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 Artificial Dirt: Microfluidic Substrates for Nematode Neurobiology and Behavior

2008 ◽  
Vol 99 (6) ◽  
pp. 3136-3143 ◽  
Author(s):  
S. R. Lockery ◽  
K. J. Lawton ◽  
J. C. Doll ◽  
S. Faumont ◽  
S. M. Coulthard ◽  
...  
Keyword(s):  
High Resolution ◽  
Optical Recording ◽  
Nematode Caenorhabditis Elegans ◽  
Free Living ◽  
Soil Matrix ◽  
C Elegans ◽  
New Class ◽  
Free Living Nematode ◽  
Neuronal Imaging ◽  
And Behavior

With a nervous system of only 302 neurons, the free-living nematode Caenorhabditis elegans is a powerful experimental organism for neurobiology. However, the laboratory substrate commonly used in C. elegans research, a planar agarose surface, fails to reflect the complexity of this organism's natural environment, complicates stimulus delivery, and is incompatible with high-resolution optophysiology experiments. Here we present a new class of microfluidic devices for C. elegans neurobiology and behavior: agarose-free, micron-scale chambers and channels that allow the animals to crawl as they would on agarose. One such device mimics a moist soil matrix and facilitates rapid delivery of fluid-borne stimuli. A second device consists of sinusoidal channels that can be used to regulate the waveform and trajectory of crawling worms. Both devices are thin and transparent, rendering them compatible with high-resolution microscope objectives for neuronal imaging and optical recording. Together, the new devices are likely to accelerate studies of the neuronal basis of behavior in C. elegans.

scholarly journals Untangling Longevity, Dauer, and Healthspan in Caenorhabditis elegans Insulin/IGF-1-Signalling

Gerontology ◽  
2017 ◽  
Vol 64 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Collin Yvès Ewald ◽  
Jorge Iván Castillo-Quan ◽  
T. Keith Blackwell
Keyword(s):  
Caenorhabditis Elegans ◽  
Healthy Aging ◽  
Receptor Gene ◽  
Recent Analysis ◽  
Lifespan Extension ◽  
Extension Programs ◽  
Subsequent Work ◽  
C Elegans ◽  
Downstream Processes ◽  
Shed Light

The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematode Caenorhabditis elegans. In this organism, mutations in the insulin/IGF-1 receptor gene daf-2 or other genes in this pathway can double lifespan. Subsequent work has revealed that reduced IIS (rIIS) extends lifespan across diverse species, possibly including humans. In C. elegans, IIS also regulates development into the diapause state known as dauer, a quiescent larval form that enables C. elegans to endure harsh environments through morphological adaptation, improved cellular repair, and slowed metabolism. Considerable progress has been made uncovering mechanisms that are affected by C. elegans rIIS. However, from the beginning it has remained unclear to what extent rIIS extends C. elegans lifespan by mobilizing dauer-associated mechanisms in adults. As we discuss, recent work has shed light on this question by determining that rIIS can extend C. elegans lifespan comparably through downstream processes that are either dauer-related or -independent. Importantly, these two lifespan extension programs can be distinguished genetically. It will now be critical to tease apart these programs, because each may involve different longevity-promoting mechanisms that may be relevant to higher organisms. A recent analysis of organismal “healthspan” has questioned the value of C. elegans rIIS as a paradigm for understanding healthy aging, as opposed to simply extending life. We discuss other work that argues strongly that C. elegans rIIS is indeed an invaluable model and consider the likely possibility that dauer-related processes affect parameters associated with health under rIIS conditions. Together, these studies indicate that C. elegans and analyses of rIIS in this organism will continue to provide unexpected and exciting results, and new paradigms that will be valuable for understanding healthy aging in humans.

scholarly journals Ether Lipid Biosynthesis Promotes Lifespan Extension and Enables Diverse Prolongevity Paradigms

2021 ◽  
Author(s):  
Lucydalila Cedillo ◽  
Sainan Li ◽  
Fasih Ahsan ◽  
Sinclair Emans ◽  
Adebanjo Adedoja ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Ether Lipid ◽  
Acid Synthesis ◽  
Epidemiologic Studies ◽  
Lipid Biosynthesis ◽  
Lifespan Extension ◽  
Full Spectrum ◽  
C Elegans ◽  
Transport Chain ◽  
Biosynthetic Machinery

Biguanides, including the world's most commonly prescribed drug for type 2 diabetes, metformin, not only lower blood sugar, but also promote longevity in preclinical models. Epidemiologic studies in humans parallel these findings, indicating favorable effects of metformin on longevity and on reducing the incidence and morbidity associated with aging-related diseases, such as cancer. In spite of these promising observations, the full spectrum of the molecular effectors responsible for these health benefits remains elusive. Through unbiased genetic screening in C. elegans, we uncovered a novel role for genes necessary for ether lipid biosynthesis in the favorable effects of biguanides. We demonstrate that biguanides govern lifespan extension via a complex effect on the ether lipid landscape requires enzymes responsible for both ether lipid biogenesis and polyunsaturated fatty acid synthesis. Remarkably, loss of the ether lipid biosynthetic machinery also mitigates lifespan extension attributable to dietary restriction, target of rapamycin (TOR) inhibition, and mitochondrial electron transport chain inhibition. Furthermore, overexpression of a single, key ether lipid biosynthetic enzyme, fard-1/FAR1, is sufficient to promote lifespan extension. These findings illuminate the ether lipid biosynthetic machinery as a novel therapeutic target to promote healthy aging.

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 PROBING THE COMPLEX INTERACTIONS BETWEEN DIET, DISEASE, AND AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S67-S67
Author(s):  
Rozalyn Anderson
Keyword(s):  
Food Intake ◽  
Dietary Restriction ◽  
Caloric Intake ◽  
Nutrient Sensing ◽  
Laboratory Animals ◽  
Lifespan Extension ◽  
Dietary Composition ◽  
Biological Interactions ◽  
Nutrient Response ◽  
Complex Interactions

Abstract Nutrient response pathways are conserved modifiers of longevity, and dietary restriction is the most studied intervention for slowing aging in laboratory animals. For many years it was believed that lifespan extension from dietary restriction was tightly linked to total caloric intake. Recent evidence suggests that the interaction between diet and aging is more complex than this, however, with nutrient sensing, dietary composition, and circadian components all playing a role. This symposium will delve into some of the complex biological interactions linking food intake, lifespan, and diseases of aging.

scholarly journals Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C. elegans

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yanan Sun ◽  
Meijiao Li ◽  
Dongfeng Zhao ◽  
Xin Li ◽  
Chonglin Yang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Food Intake ◽  
Aging Process ◽  
Lifespan Extension ◽  
C Elegans ◽  
Cathepsin Proteases ◽  
Age Dependent ◽  
Genes Encoding ◽  
Degradation Activity ◽  
Lifespan Regulation

Lysosomes play important roles in cellular degradation to maintain cell homeostasis. In order to understand whether and how lysosomes alter with age and contribute to lifespan regulation, we characterized multiple properties of lysosomes during the aging process in C. elegans. We uncovered age-dependent alterations in lysosomal morphology, motility, acidity and degradation activity, all of which indicate a decline in lysosome function with age. The age-associated lysosomal changes are suppressed in the long-lived mutants daf-2, eat-2 and isp-1, which extend lifespan by inhibiting insulin/IGF-1 signaling, reducing food intake and impairing mitochondrial function, respectively. We found that 43 lysosome genes exhibit reduced expression with age, including genes encoding subunits of the proton pump V-ATPase and cathepsin proteases. The expression of lysosome genes is upregulated in the long-lived mutants, and this upregulation requires the functions of DAF-16/FOXO and SKN-1/NRF2 transcription factors. Impairing lysosome function affects clearance of aggregate-prone proteins and disrupts lifespan extension in daf-2, eat-2 and isp-1 worms. Our data indicate that lysosome function is modulated by multiple longevity pathways and is important for lifespan extension.

scholarly journals Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics in C. elegans

2019 ◽  
Author(s):  
Yue Zhang ◽  
Anne Lanjuin ◽  
Suvagata Roy Chowdhury ◽  
Meeta Mistry ◽  
Carlos G. Silva Garcia ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Lifespan Extension ◽  
Ampk Activation ◽  
Aging Effects ◽  
C Elegans ◽  
Genes Encoding ◽  
The Central Nervous System ◽  
Amp Activated Protein Kinase

AbstractTarget of rapamycin complex 1 (TORC1) and AMP-activated protein kinase (AMPK) antagonistically modulate metabolism and aging. However, how they coordinate to determine longevity and if they act via separable mechanisms is unclear. Here, we show that neuronal AMPK is essential for lifespan extension from TORC1 inhibition, and that TORC1 suppression increases lifespan cell non autonomously via distinct mechanisms from global AMPK activation. Lifespan extension by null mutations in genes encoding raga-1 (RagA) or rsks-1 (S6K) is fully suppressed by neuronal-specific rescues. Loss of RAGA-1 increases lifespan via maintaining mitochondrial fusion. Neuronal RAGA-1 abrogation of raga-1 mutant longevity requires UNC-64/syntaxin, and promotes mitochondrial fission cell nonautonomously. Finally, deleting the mitochondrial fission factor DRP-1 renders the animal refractory to the pro-aging effects of neuronal RAGA-1. Our results highlight a new role for neuronal TORC1 in cell nonautonomous regulation of longevity, and suggest TORC1 in the central nervous system might be targeted to promote healthy aging.

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.

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