Autophagy and Aging - Week 7 Overview

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Questions and Answers

What is a consequence of inadequate turnover of organelles in aging cells?

Higher levels of free radicals (correct)

Increased energy production

Reduced protein damage

Increased macroautophagy activity

How does maintained insulin signaling affect macroautophagy in aging cells?

It enhances glucagon activity.

It decreases mTOR activation.

It promotes autophagosome formation.

It inhibits macroautophagy. (correct)

Which diet has been shown to regenerate various cell types and extend longevity in mice?

High protein diet

Low-fat diet

Caloric excess diet

Fasting Mimicking Diet (FMD) (correct)

What is a key function of V-ATPase in autophagic processes?

To pump H+ into the lysosomal lumen Signup and view all the answers

Why might glucagon's stimulatory effect on macroautophagy be compromised in old cells?

Due to maintained negative signaling through the insulin receptor Signup and view all the answers

What effect does a decline in macroautophagy have on aging cells?

Reduces cellular turnover Signup and view all the answers

What health benefits were observed in mice fed a Fasting Mimicking Diet?

Improved learning and memory Signup and view all the answers

What major mechanism is activated by the insulin receptor that affects macroautophagy?

Activation of the mTOR pathway Signup and view all the answers

What role does mTORC1 play in the regulation of protein synthesis?

Inhibitor of eIF4E assembly Signup and view all the answers

Which of the following components is not part of the mTORC1 complex?

S6K1 Signup and view all the answers

How does mTORC1 affect 4EBP in regards to mRNA translation?

dissociates from eIF4E to enable translation Signup and view all the answers

Which of the following is a regulator of mTORC1 activity?

Rapamycin Signup and view all the answers

What is the result of mTORC1 signaling to S6K?

Liberation of eIF4E Signup and view all the answers

What class of mRNA does mTORC1 signaling particularly affect based on recent analyses?

Translated mRNAs Signup and view all the answers

Which amino acid is mentioned as a key regulator of mTORC1 activation?

Leucine Signup and view all the answers

What is the function of Ragulator in relation to mTORC1?

Releases GTP from RagC Signup and view all the answers

What is the primary role of the low pH in lysosomes?

It promotes the activity of acid hydrolases. Signup and view all the answers

Which of the following transporters is known for sensing luminal arginine?

SLC38A9 Signup and view all the answers

What is the primary role of mTORC1 in cellular processes?

It coordinates stimuli that promote ribosome production. Signup and view all the answers

What is one function of mTORC1 in cells?

Promotes protein synthesis through phosphorylation of effectors. Signup and view all the answers

Which of the following enzymes is responsible for converting fatty acyl-carnitine back to fatty acyl-CoA?

CPT2 Signup and view all the answers

How does cholesterol exit the lysosome?

Through NPC1/NPC2 proteins and SCARB2. Signup and view all the answers

In beta-oxidation, how many carbons are processed at a time from fatty acids?

Two carbons at a time Signup and view all the answers

What potential problem does solute efflux in lysosomes help prevent?

Increased lysosomal hydrostatic pressure. Signup and view all the answers

In which location do proton-coupled amino acid transporters primarily function?

On the lysosomal membrane and in the small intestine. Signup and view all the answers

What must occur before fatty acids can undergo oxidation in the mitochondria?

They must be activated and transported to the mitochondrion. Signup and view all the answers

Which effector does mTORC1 directly phosphorylate to promote mRNA translation initiation?

p70S6 Kinase 1 Signup and view all the answers

Which of the following components is liberated as a result of mTORC1 signaling?

eIF4E Signup and view all the answers

What is the effect of S6K1 phosphorylation in the context of protein synthesis?

It activates substrates that promote mRNA translation initiation. Signup and view all the answers

What is the primary product of each round of fatty acid oxidation?

One Acetyl-CoA Signup and view all the answers

What role does the thiolase enzyme play in fatty acid metabolism?

It catalyzes the reverse reaction when the R-group is a hydrogen. Signup and view all the answers

Which reaction in beta oxidation is similar to the fumarase reaction of the citric acid cycle?

Reaction 2 Signup and view all the answers

What are the end products after each cycle of fatty acid oxidation?

One FADH2, one NADH, one Acetyl-CoA, and one fatty acid shortened by two carbons. Signup and view all the answers

What form of fatty acyl-CoA ligase begins the activation of fatty acids?

Long-chain fatty acyl-CoA ligase Signup and view all the answers

Study Notes

Week 7, Lecture 11

Autophagy Failure in Aging: Possible causes and consequences of autophagy failure in old organisms are depicted in a schematic model.
Autophagic Vacuoles and Lipofuscin: Accumulation of autophagic vacuoles may occur due to the inability of lipofuscin-loaded lysosomes to fuse and degrade sequestered content.
Macroautophagy Enhancers and Glucagon: The formation of autophagosomes in old cells might be reduced because of the inability of macroautophagy enhancers (like glucagon) to fully activate the pathway. This effect is compromised in aged cells because of maintained negative signalling via the insulin receptor even under baseline conditions.
Maintaining Insulin Signaling: Maintaining insulin signaling activates mTOR, a key repressor of macroautophagy.
Inadequate Organelle Turnover: Inadequate turnover of organelles (like mitochondria) in aging cells can increase free radical levels, leading to protein damage.
Insulin Receptor and Free Radicals: Free radicals can further potentiate inhibitory signalling through the insulin receptor.
Age-Dependent Decline in Macroautophagy: An age-related decrease in macroautophagy can compromise the energetic balance of aging cells.
Autophagy and Longevity: Autophagy plays a critical role in maintaining longevity through multiple processes.
Pro-longevity Mechanisms: Factors like neural protection, cancer blockage, anti-inflammatory signaling, genomic integrity, stem cell rejuvenation, and cellular/tissue homeostasis all contribute to pro-longevity mechanisms.
Periodic Fasting and Regeneration: Periodic fasting mimicking diets (FMD) in mice promote multi-system regeneration, improving markers for rejuvenation, adiposity, inflammatory diseases, and cognitive function.
Lipid and Nucleic Acid Synthesis: mTORC1 plays a crucial role in controlling protein, lipid, and nucleic acid synthesis.
Anabolism and Catabolism: mTORC1 regulates the balance between anabolism and catabolism in response to environmental conditions.
mTORC1 Substrate: The mTORC1 substrate 4EBP (eukaryotic initiation factor 4E binding protein) is unrelated to S6K1 and interferes with translation.
Ribosome Production and Regulation: mTORC1 positively regulates ribosomal RNA transcription and protein synthesis as a way to control stimulus like stressors that lead to increased ribosome production.
mTORC1 Regulation of mRNA Translation: mTORC1 has a key role in regulating mRNA translation by its effect on S6K and 4EBP which affects the biogenesis of ribosomes.
Amino Acid Sensing and Lysosome: Arginine activation of SLC38A9 triggers the recruitment of mTORC1 to the lysosome surface and activates it in this process.
Fatty Acid-Carnitine Shuttle: The process of transporting fatty acids into the mitochondria for oxidation (β-oxidation).
Fatty Acid Pathway Stages: Different stages exist: 1. Oxidation, 2. Hydration, 3. Oxidation, and 4. Cleavage.
Enzyme Roles in Fatty Acid Oxidation: Enzymes like acyl-CoA dehydrogenase, enoyl-CoA hydratase, and hydroxyacyl-CoA dehydrogenase are vital in fatty acid oxidation, leading to acetyl-CoA, FADH2, NADH generation.
Fatty Acid Oxidation Reactions: The four beta-oxidation reactions, where each round shortens the fatty acid chain reducing it to acetyl-CoA, also produce FADH2 and NADH.

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Description

Explore the effects of autophagy failure in aging organisms, including causes, consequences, and the role of insulin signaling. This quiz addresses key concepts such as the accumulation of autophagic vacuoles and the impact of macroautophagy enhancers like glucagon. Understand the relationship between inadequate organelle turnover and oxidative stress in aged cells.