Autophagy!
Can anybody tell me anything about autophagy without looking it up?
We want a thread just about autophagy, so GO!
Post stuff about it.
We'll go as in depth or as basic as you want.
...Most (non training) days, I fast and while the amount of time varies- I generally only consume calories after a certain time. It's not exactly one meal, but it's a slow burn of whatever I want, dinner, whatever else I want and then bed. That's not to state that I'm going to bed right after eating, as a rule that's unwise. Some foods digest while sleeping better than others and most people benefit from a couple/ few hours between eating and sleeping.
More later.
Intermittent Fasting Improves Health Without Altering the Body’s Core Clock
For the first time, scientists have studied the early effects of time-restricted feeding on the daily periodic oscillations of metabolites and genes in muscle, and metabolites in blood. The findings by scientists at the University of Copenhagen, the Australian Catholic University and Karolinska Institutet find that time-restricted feeding does not influence the muscle’s core clock, and opens the door to more research on how these observed changes improve health.
When it comes to metabolic health, it’s not just what you eat, it’s when you eat it. Studies have shown that one effective means of losing weight and tackling obesity is to reduce the number of hours in the day that you eat. Time-restricted feeding – otherwise known as intermittent fasting – has also been shown to improve health even before weight loss kicks in.
The biological explanation for the phenomenon remains poorly understood. So scientists from the University of Copenhagen, the Australian Catholic University and Karolinska Institutet investigated the body’s early adaptations to time-restricted feeding. Their study identified a number of key changes in the genetic activity of muscles, as well as the content of muscle fats and proteins, which could explain the positive impact of time-restricted feeding.
Principal component analysis (PCA) of samples based on skeletal muscle genes (a), skeletal muscle metabolites (b), and serum metabolites (c), with color indicating sampling time. Circle indicates extended feeding (EXF), and triangle indicates time-restricted feeding (TRF). t-SNE clustering of periodic transcripts in skeletal muscle after EXF (d), and TRF (e). Periodic metabolites in skeletal muscle after EXF (f), and TRF (g), and serum metabolites after EXF (h), and TRF (i). n = 11 participants. Credit: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen
Novel insights on short-term time-restricted feeding
The study is the first time scientists have examined the oscillations of metabolites in skeletal muscle and in blood, as well as gene expression in skeletal muscle after time-restricted feeding. By focusing on the short-term and early effects of time-restricted feeding, the goal was to disentangle the signals that govern health from those associated with weight loss.
“We observe that the rhythm of skeletal muscle core clock genes is unchanged by time-restricted feeding, suggesting that any differences are driven more by diet, rather than inherent rhythms,” says Postdoc Leonidas Lundell, from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.
“We also see that the metabolite profile of skeletal muscle switches from being predominantly lipid-based, to amino acid-based, after time-restricted feeding. This coincides with changes in rhythmicity of amino acid transporters, indicating that part of the amino acid profile could be due to absorption from the blood.”
Research Fellow Evelyn Parr from the Mary MacKillop Institute for Health Research at the Australian Catholic University, adds: “Our research is an important step towards understanding how time-restricted eating can improve metabolic health, while bridging the gap between animal models and human intervention studies. It was important to capture these early metabolic responses before assessing what changes might occur after a longer period following a time-restricted feeding pattern.”
Eating behavior does not impact the body’s core clock
In the study, 11 men with overweight/obesity were assigned one of two eating protocols for a period of five days, either unrestricted feeding, or eight-hours of time restricted feeding. On the fifth day, samples were taken every four hours for a full day. After a 10-day break, they repeated the experiment following the other eating protocol.
After each intervention, the team of scientists studied the gene expression in muscles, as well as the profile of metabolites – molecules that are formed through metabolic processes – in the blood and muscles.
They discovered that time-restricted feeding changed the rhythmic concentration of metabolites in blood and muscle. Time-restricted feeding also influenced the rhythmic expression of genes expressed by muscle, particularly those responsible for helping the transport of amino acids, the building blocks of proteins.
Critically, the study showed that time-restricted feeding did not alter the muscle’s core clock – the cell’s inbuilt metronome that regulates its daily cycle of activity. This suggests that the altered rhythmicity of metabolite and gene expression caused by time-restricted feeding could be responsible for the positive health impact.
“Our findings open new avenues for scientists who are interested in understanding the causal relationship between time-restricted feeding and improved metabolic health. These insights could help develop new therapies to improve the lives of people who live with obesity,” says Professor Juleen Zierath from Karolinska Institutet and CBMR at the University of Copenhagen.
Reference: “Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression” by Leonidas S. Lundell, Evelyn B. Parr, Brooke L. Devlin, Lars R. Ingerslev, Ali Altıntaş, Shogo Sato, Paolo Sassone-Corsi, Romain Barrès, Juleen R. Zierath and John A. Hawley, 16 September 2020, Nature Communications.
DOI: 10.1038/s41467-020-18412-w
source: scitechdaily.com
Parkinson’s, Cancer, and Type 2 Diabetes Share a Key Element That Drives Disease
TOPICS:CancerCell BiologyDiabetesGeneticsMolecular BiologyParkinson's DiseaseSalk Institute
By SALK INSTITUTE JULY 15, 2021
Parkin Protein
Parkin protein (green signal) is in a different part of the cell than the mitochondria (red signal) at time 0 (left image) but then co-localizes with the mitochondria after 60 minutes (right image). Credit: Salk Institute
Enzyme with central role in cancer and type 2 diabetes also activates “clean-up” protein in Parkinson’s.
When cells are stressed, chemical alarms go off, setting in motion a flurry of activity that protects the cell’s most important players. During the rush, a protein called Parkin hurries to protect the mitochondria, the power stations that generate energy for the cell. Now Salk researchers have discovered a direct link between a master sensor of cell stress and Parkin itself. The same pathway is also tied to type 2 diabetes and cancer, which could open a new avenue for treating all three diseases.
“Our findings represent the earliest step in Parkin’s alarm response that anyone’s ever found by a long shot. All the other known biochemical events happen at one hour; we’ve now found something that happens within five minutes,” says Professor Reuben Shaw, director of the NCI-designated Salk Cancer Center and senior author of the new work, detailed in Science Advances on April 7, 2021. “Decoding this major step in the way cells dispose of defective mitochondria has implications for a number of diseases.”
Parkin’s job is to clear away mitochondria that have been damaged by cellular stress so that new ones can take their place, a process called mitophagy. However, Parkin is mutated in familial Parkinson’s disease, making the protein unable to clear away damaged mitochondria. While scientists have known for some time that Parkin somehow senses mitochondrial stress and initiates the process of mitophagy, no one understood exactly how Parkin was first sensing problems with the mitochondria—Parkin somehow knew to migrate to the mitochondria after mitochondrial damage, but there was no known signal to Parkin until after it arrived there.
Shaw’s lab, which is well known for their work in the fields of metabolism and cancer, spent years intensely researching how the cell regulates a more general process of cellular cleaning and recycling called autophagy. About ten years ago, they discovered that an enzyme called AMPK, which is highly sensitive to cellular stress of many kinds, including mitochondrial damage, controls autophagy by activating an enzyme called ULK1.
Following that discovery, Shaw and graduate student Portia Lombardo began searching for autophagy-related proteins directly activated by ULK1. They screened about 50 different proteins, expecting about 10 percent to fit. They were shocked when Parkin topped the list. Biochemical pathways are usually very convoluted, involving up to 50 participants, each activating the next. Finding that a process as important as mitophagy is initiated by only three participants—first AMPK, then ULK1, then Parkin—was so surprising that Shaw could scarcely believe it.
To confirm the findings were correct, the team used mass spectrometry to reveal precisely where ULK1 was attaching a phosphate group to Parkin. They found that it landed in a new region other researchers had recently found to be critical for Parkin activation but hadn’t known why. A postdoctoral fellow in Shaw’s lab, Chien-Min Hung, then did precise biochemical studies to prove each aspect of the timeline and delineated which proteins were doing what, and where. Shaw’s research now begins to explain this key first step in Parkin activation, which Shaw hypothesizes may serve as a “heads-up” signal from AMPK down the chain of command through ULK1 to Parkin to go check out the mitochondria after a first wave of incoming damage, and, if necessary, trigger destruction of those mitochondria that are too gravely damaged to regain function.
The findings have wide-ranging implications. AMPK, the central sensor of the cell’s metabolism, is itself activated by a tumor suppressor protein called LKB1 that is involved in a number of cancers, as established by Shaw in prior work, and it is activated by a type 2 diabetes drug called metformin. Meanwhile, numerous studies show that diabetes patients taking metformin exhibit lower risks of both cancer and aging comorbidities. Indeed, metformin is currently being pursued as one of the first ever “anti-aging” therapeutics in clinical trials.
“The big takeaway for me is that metabolism and changes in the health of your mitochondria are critical in cancer, they’re critical in diabetes, and they’re critical in neurodegenerative diseases,” says Shaw, who holds the William R. Brody Chair. “Our finding says that a diabetes drug that activates AMPK, which we previously showed can suppress cancer, may also help restore function in patients with neurodegenerative disease. That’s because the general mechanisms that underpin the health of the cells in our bodies are way more integrated than anyone could have ever imagined.”
Reference: “AMPK/ULK1-mediated phosphorylation of Parkin ACT domain mediates an early step in mitophagy” by Chien-Min Hung, Portia S. Lombardo, Nazma Malik, Sonja N. Brun, Kristina Hellberg, Jeanine L. Van Nostrand, Daniel Garcia, Joshua Baumgart, Ken Diffenderfer, John M. Asara and Reuben J. Shaw, 7 April 2021, Science Advances.
DOI: 10.1126/sciadv.abg4544
Source: scitechdaily.com
...ever heard of #autophagy?
This lowers our inflammatory profile more than anything else, I think. It's... Very important.
Trying it is free, ultra simple and results are all but immediate. I'm also going to start endorsing some supplements once I've got strategic partnerships, but one of the complexes to try is #resveratrol. Want to age backwards? Everybody needs to... More later and feel free to register a user name and post on forum. It's entirely free, and we don't censor people like Facebook.
Also, everybody needs to watch this podcast!
Don't be a noob! Watch the entire thing. Save lives; aging is fake news.
I will give it a try. Has to do with cell function. 2.. auto body's ability to respond Quickly with out any other cellular influence. Ex Macrophages. Close maybe?
Time-Restricted Eating Has Important Health Benefits – Even With Infectious Diseases Such As COVID-19
Not everyone benefits equally from time-restricted eating, as health benefits depend on age and sex.
Time-restricted eating (TRE), a dietary regimen that restricts eating to specific hours, has garnered increased attention in weight-loss circles. A new study by Salk scientists further shows that TRE confers multiple health benefits besides weight loss. The study also shows that these benefits may depend on sex and age.
Most TRE studies focus on weight loss in young male mice, but Salk scientists wanted to determine whether TRE confers additional benefits on other populations. Their findings, published in Cell Reports on August 17, 2021, show that while age and sex do affect the outcomes of TRE, the eating strategy delivers multiple health benefits for young and old of both sexes, and indicates that TRE may be a valuable intervention for type 2 diabetes, fatty liver disease and liver cancer, and even infectious diseases such as COVID-19, in humans.
“For many TRE clinical interventions, the primary outcome is weight loss, but we’ve found that TRE is good not only for metabolic disease but also for increased resilience against infectious diseases and insulin resistance,” says Satchidananda Panda, a professor in Salk’s Regulatory Biology Laboratory and holder of the Rita and Richard Atkinson Chair.
A new study by Salk scientists shows that time-restricted eating (TRE) confers multiple health benefits besides weight loss. The study also shows that these benefits may depend on sex and age. Credit: Salk Institute
Glucose intolerance is the first step on a slippery slope to non–
Breaking the conventional young-male-mice mold, the researchers fed a high-fat, high-sugar diet to male and female mice of two age groups (equivalent to 20- and 42-year-old humans), restricting eating to nine hours per day. The team ran tests to ascertain how age and sex affect the outcomes of TRE on a variety of health parameters: fatty liver disease; glucose regulation; muscle mass, performance and endurance; and survival of sepsis, a life-threatening response to infection. They also took the rare step of matching their lab conditions to the animals’ circadian clocks (mice sleep during the day and rise at night), often working via night-vision goggles and specialized lighting.
Analyzing the tissues of mice on TRE to ascertain their chemical makeup and processes, the researchers found that regardless of age, sex or weight loss profile, TRE strongly protected against fatty liver disease, a condition that affects up to 100 million Americans and for which no medicine has been approved.
“This was our first time studying female mice, and we weren’t sure what to expect,” says first author Amandine Chaix, a former staff scientist in the Panda lab and now an assistant professor at the University of Utah. “We were surprised to find that, although the females on TRE were not protected from weight gain, they still showed metabolic benefits, including less-fatty livers and better-controlled blood sugar.”
Oral glucose tolerance tests given to mice after 16 hours of fasting indicated that TRE was associated with a lower increase in blood glucose and a faster return to normal blood sugar levels in both young and middle-aged males, with a significant improvement in glucose tolerance in young and middle-aged females. Similarly, middle-aged females and males on TRE were able to restore normal blood sugar levels more efficiently than control mice, who had food available at all times. This finding indicates that TRE may be a low- or no-cost, user-friendly way to prevent or treat diabetes, and supports the results of the lab’s 2019 study on TRE for metabolic syndrome in humans.
The researchers also found that TRE may protect both males and females from sepsis-induced death—a particular danger in ICUs, especially during the pandemic. After administering a toxin that induced a sepsis-like condition in the mice, the researchers monitored survival rates for 13 days and found that TRE protected both male and female mice from dying of sepsis.
TRE didn’t just protect against fatty liver disease, diabetes, and death from sepsis; it even enabled male mice to preserve and add muscle mass and improve muscle performance (the effect did not hold for females). This finding is particularly significant for the elderly, for whom improved muscle performance can help guard against falls.
This surprising discovery points to next steps and new questions for Panda’s lab: Does muscle mass increase because TRE helps muscles repair and regenerate better? What is the impact of TRE on muscle metabolism and regeneration?
“These are very exciting questions for us, and we look forward to studying them in more detail,” says Panda.
Reference: “Sex and age-dependent outcomes of 9 hour time-restricted feeding of a western high-fat high-sucrose diet in C57Bl/6J mice” 17 August 2021, Cell Reports.
DOI: 10.1016/j.celrep.2021.109543
Other authors on the study were Shaunak Deota, Raghav Bhardwaj and Terry Lin of Salk.
The research was supported by the American Heart Association, National Institute on Aging, Glenn Center for Aging Research and Wu-Tsai Human Performance Alliance.
source: scitechdaily.com
