#cellular aging

[medicomunicare]

Brain cancer "going APE": here is its way to resist TMZ and leave DNA repair BEReft of options

In spite of intensive research, glioblastoma remains one of the most lethal types of brain cancer. Despite there are several available medications, temozolomide (TMZ) is the front-line drug in its treatment; while TMZ effectively penetrates the brain and targets tumors, its success depends on the tumor cells attempting to repair the DNA damage caused by the drug. Unfortunately, glioblastomas…

[scienceswitch]

The Science of Aging: What Happens to Our Bodies As We Get Older?

Aging is a natural and inevitable journey that all living organisms experience. As we progress through the different stages of life, our bodies undergo profound physiological changes. These transformations reflect the complex biological choreography that shapes human development and maturation. Aging is defined as the accumulation of changes over time associated with or responsible for the…

[jenks378]

Methylene Blue : Potential Benefits For Anti-Aging, Brain Health And Mor...

[jcmarchi]

Cellular traffic congestion in chronic diseases suggests new therapeutic targets

New Post has been published on https://thedigitalinsider.com/cellular-traffic-congestion-in-chronic-diseases-suggests-new-therapeutic-targets/

Cellular traffic congestion in chronic diseases suggests new therapeutic targets

Chronic diseases like Type 2 diabetes and inflammatory disorders have a huge impact on humanity. They are a leading cause of disease burden and deaths around the globe, are physically and economically taxing, and the number of people with such diseases is growing.

Treating chronic disease has proven difficult because there is not one simple cause, like a single gene mutation, that a treatment could target. At least, that’s how it has appeared to scientists. However, new research from MIT professor of biology and Whitehead Institute for Biomedical Research member Richard Young and colleagues, published in the journal Cell on Nov. 27, reveals that many chronic diseases have a common denominator that could be driving their dysfunction: reduced protein mobility. 

What this means is that around half of all proteins active in cells slow their movement when cells are in a chronic disease state, reducing the proteins’ functions. The researchers’ findings suggest that protein mobility may be a linchpin for decreased cellular function in chronic disease, making it a promising therapeutic target.

In their paper, Young and colleagues in his lab, including MIT postdoc Alessandra Dall’Agnese, graduate students Shannon Moreno and Ming Zheng, and Research Scientist Tong Ihn Lee, describe their discovery of this common mobility defect, which they call proteolethargy; explain what causes the defect and how it leads to dysfunction in cells; and propose a new therapeutic hypothesis for treating chronic diseases.

“I’m excited about what this work could mean for patients,” says Dall’Agnese. “My hope is that this will lead to a new class of drugs that restore protein mobility, which could help people with many different diseases that all have this mechanism as a common denominator.”

“This work was a collaborative, interdisciplinary effort that brought together biologists, physicists, chemists, computer scientists and physician-scientists,” Lee says. “Combining that expertise is a strength of the Young lab. Studying the problem from different viewpoints really helped us think about how this mechanism might work and how it could change our understanding of the pathology of chronic disease.”

Commuter delays cause work stoppages in the cell

How do proteins moving more slowly through a cell lead to widespread and significant cellular dysfunction? Dall’Agnese explains that every cell is like a tiny city, with proteins as the workers who keep everything running. Proteins have to commute in dense traffic in the cell, traveling from where they are created to where they work. The faster their commute, the more work they get done. Now, imagine a city that starts experiencing traffic jams along all the roads. Stores don’t open on time, groceries are stuck in transit, meetings are postponed. Essentially all operations in the city are slowed.

The slowdown of operations in cells experiencing reduced protein mobility follows a similar progression. Normally, most proteins zip around the cell bumping into other molecules until they locate the molecule they work with or act on. The slower a protein moves, the fewer other molecules it will reach, and so the less likely it will be able to do its job. Young and colleagues found that such protein slowdowns lead to measurable reductions in the functional output of the proteins. When many proteins fail to get their jobs done in time, cells begin to experience a variety of problems — as they are known to do in chronic diseases.

Discovering the protein mobility problem

Young and colleagues first suspected that cells affected in chronic disease might have a protein mobility problem after observing changes in the behavior of the insulin receptor, a signaling protein that reacts to the presence of insulin and causes cells to take in sugar from blood. In people with diabetes, cells become less responsive to insulin — a state called insulin resistance — causing too much sugar to remain in the blood. In research published on insulin receptors in Nature Communications in 2022, Young and colleagues reported that insulin receptor mobility might be relevant to diabetes.

Knowing that many cellular functions are altered in diabetes, the researchers considered the possibility that altered protein mobility might somehow affect many proteins in cells. To test this hypothesis, they studied proteins involved in a broad range of cellular functions, including MED1, a protein involved in gene expression; HP1α, a protein involved in gene silencing; FIB1, a protein involved in production of ribosomes; and SRSF2, a protein involved in splicing of messenger RNA. They used single-molecule tracking and other methods to measure how each of those proteins moves in healthy cells and in cells in disease states. All but one of the proteins showed reduced mobility (about 20-35 percent) in the disease cells. 

“I’m excited that we were able to transfer physics-based insight and methodology, which are commonly used to understand the single-molecule processes like gene transcription in normal cells, to a disease context and show that they can be used to uncover unexpected mechanisms of disease,” Zheng says. “This work shows how the random walk of proteins in cells is linked to disease pathology.”

Moreno concurs: “In school, we’re taught to consider changes in protein structure or DNA sequences when looking for causes of disease, but we’ve demonstrated that those are not the only contributing factors. If you only consider a static picture of a protein or a cell, you miss out on discovering these changes that only appear when molecules are in motion.”

Can’t commute across the cell, I’m all tied up right now

Next, the researchers needed to determine what was causing the proteins to slow down. They suspected that the defect had to do with an increase in cells of the level of reactive oxygen species (ROS), molecules that are highly prone to interfering with other molecules and their chemical reactions. Many types of chronic-disease-associated triggers, such as higher sugar or fat levels, certain toxins, and inflammatory signals, lead to an increase in ROS, also known as an increase in oxidative stress. The researchers measured the mobility of the proteins again, in cells that had high levels of ROS and were not otherwise in a disease state, and saw comparable mobility defects, suggesting that oxidative stress was to blame for the protein mobility defect.

The final part of the puzzle was why some, but not all, proteins slow down in the presence of ROS. SRSF2 was the only one of the proteins that was unaffected in the experiments, and it had one clear difference from the others: its surface did not contain any cysteines, an amino acid building block of many proteins. Cysteines are especially susceptible to interference from ROS because it will cause them to bond to other cysteines. When this bonding occurs between two protein molecules, it slows them down because the two proteins cannot move through the cell as quickly as either protein alone. 

About half of the proteins in our cells contain surface cysteines, so this single protein mobility defect can impact many different cellular pathways. This makes sense when one considers the diversity of dysfunctions that appear in cells of people with chronic diseases: dysfunctions in cell signaling, metabolic processes, gene expression and gene silencing, and more. All of these processes rely on the efficient functioning of proteins — including the diverse proteins studied by the researchers. Young and colleagues performed several experiments to confirm that decreased protein mobility does in fact decrease a protein’s function. For example, they found that when an insulin receptor experiences decreased mobility, it acts less efficiently on IRS1, a molecule to which it usually adds a phosphate group.

From understanding a mechanism to treating a disease

Discovering that decreased protein mobility in the presence of oxidative stress could be driving many of the symptoms of chronic disease provides opportunities to develop therapies to rescue protein mobility. In the course of their experiments, the researchers treated cells with an antioxidant drug — something that reduces ROS — called N-acetyl cysteine and saw that this partially restored protein mobility. 

The researchers are pursuing a variety of follow-ups to this work, including the search for drugs that safely and efficiently reduce ROS and restore protein mobility. They developed an assay that can be used to screen drugs to see if they restore protein mobility by comparing each drug’s effect on a simple biomarker with surface cysteines to one without. They are also looking into other diseases that may involve protein mobility, and are exploring the role of reduced protein mobility in aging.

“The complex biology of chronic diseases has made it challenging to come up with effective therapeutic hypotheses,” says Young. “The discovery that diverse disease-associated stimuli all induce a common feature, proteolethargy, and that this feature could contribute to much of the dysregulation that we see in chronic disease, is something that I hope will be a real game-changer for developing drugs that work across the spectrum of chronic diseases.”

[landwriter]

🍋 What’s your favorite spicier trope to write?

fruit fic asks!

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[deva-arts]

Vincent has dark roots and white hair. Does he dye it?

Nope. His hair just fades in that color past a certain length. If he were to let it all grow out instead of shaving the sides all the time, it would all look white and spiky.

(Similarly, if he buzzed it all off, it would be black.)

[fish-bowl-2]

Thoughts on Ed Edd n Eddy being a Millennium era (1999 - 2000) period piece?

[cleverthylacine]

be pro-ageing but not pro-biological damage.  It’s fine to admire signs of a life well lived but just like I can admire scars without wanting to have events in my life that lead to them, I admire healthy aging but I’m not a fan of collagen loss or bone loss or sun damage.  I do many things to keep myself looking younger than my age and am pleased when people are surprised by it, but that is largely because I do not like having uncomfortable skin or feeling like a single fall will kill me.

There is much to be admired in the wisdom gained from living a long life; if you have not died by the time you’re 70 or 80 or 90 or 100+, you must have done something right and you must have some survival skills.

But you can admire the life experience and not the fragility.

be pro-aging but wear sun screen. sun protection is not beauty industry propaganda it will save you. wear it. or else.

[theearthforce]

Clear cellular memory

After releasing negative energy and obsolete programs during a energy healing session, please make sure the cellular memory is cleared as well, as it helps prevent issues from returning.

Science has provided supporting evidence, for example:

'Fat cells have excellent memory. Researchers published a study in Nature that explains how that memory works and why it is so persistent. The work describes the genetic and cellular mechanisms that make the "Yo-Yo effect," a common phenomenon where a person can lose weight, but it returns right away.

...

The core of why fat cells are so stubborn comes down to epigenetics — a relatively new area of study that shows how long-ago events, experiences, or environmental exposures can affect a person’s genetic information. For example, research has shown that someone who survived trauma as a child — say abuse or neglect — will suffer long-lasting changes to their DNA, which, in turn can affect cells, potentially manifesting as diseases or chronic conditions. These genetic changes can even be passed on through the generations.'

from: Fat Cells Can Retain a Genetic Memory — Even After Weight Loss, Discover Magazine, 27 Nov 2024 [x]

[primepaginequotidiani]

PRIMA PAGINA Corriere Delle Alpi di Oggi sabato, 14 dicembre 2024

[medicomunicare]

An UBIquitous Parkin to take a NAP iSINT BAD while OPTN' for cargo hold: but TANK-binding will lead to a mit-o-loss

There are several pathways to induce mitophagy, or the self-degradation of irreversibly damaged cellular mitochondria. The most well-characterized of these depends on proteins called PINK1 and Parkin, two proteins actively involved in the abnormalities of brain cells affected by Parkinson’s disease. Two other proteins, TFEB and HKDC1, play a key role in the maintenance of both mitochondria and…

[justposting1]

DIY Open Wardrobe Organisation Ideas for a Bright Bedroom with Light and Airy Window Curtains

Bring Style and Functionality Together: Open Wardrobe Tips for a Light-Filled Bedroom Haven Creating a bedroom that feels light, airy, and organized is a dream for many. An open wardrobe can contribute to this aesthetic, offering a stylish yet practical storage solution that blends seamlessly with bright and minimalist decor. This guide will explore how to organize an open wardrobe while…

[victorvmx]

Nagano Tonic: Natural Weight Loss & Energy Boost Formula

click here to buy https://bit.ly/4f2MtRI

[bitcoinversus]

BioTechnology: Washington Professor Says Future Humans May Live Up to 500 Years

Pedro Domingos, a professor emeritus at the University of Washington and author of The Master Algorithm and 2040, envisions a future where humans may achieve unprecedented lifespans, potentially living up to 500 years. Future humans will have much bigger brains, live to 500 and be children for the first 50 years.— Pedro Domingos (@pmddomingos) October 20, 2024 He suggests that such longevity…

[kevinbutlerweb]

Increase Your Power and Enhance Your Wellness with NAD Infusion

Are you feeling drained pipes and lacking the power to tackle your daily jobs? Have you been looking for a natural way to boost your wellness and general health? Look no more than NAD infusion therapy-- an advanced treatment that can assist increase your power levels and revitalize your body from within.NAD, or Nicotinamide Adenine Dinucleotide, is a coenzyme discovered in every cell of your body that plays an essential function in power manufacturing. As we age, our NAD levels naturally decline, causing reduced power levels and general vitality. NAD mixture therapy functions by directly providing this necessary coenzyme right into your bloodstream, bypassing the digestion system for maximum absorption and effectiveness.One of the key benefits of NAD mixture treatment is its capability to considerably raise energy levels. By renewing your body's NAD shops, you can experience a visible boost in stamina, emphasis, and psychological clearness. Bid farewell to afternoon downturns and hey there to continual energy throughout the day.But the benefits of NAD infusion therapy extend much beyond just enhanced energy levels. This innovative treatment has actually been shown to boost general health and wellness and health in various methods. From sustaining mobile repair work and regeneration to boosting cognitive function and mood stability, NAD mixture therapy supplies a comprehensive method to enhancing your wellness from the within out.Unlike traditional energy-boosting techniques like caffeine or stimulants that offer short-term solutions with prospective negative effects, NAD infusion treatment takes an alternative strategy to wellness. By attending to the source of reduced power levels-- decreasing NAD degrees-- this treatment sustains your body's natural processes for lasting outcomes with no harmful ingredients or chemicals.If you prepare to experience the transformative power of NAD infusion therapy on your own, getting going is simpler than you think. Just arrange an assessment with a certified doctor that focuses on this cutting-edge treatment. During your preliminary visit, you'll discuss your wellness objectives and medical history to identify if NAD mixture treatment is best for you.Once accepted for therapy, you can look forward to kicking back sessions where NAD is provided intravenously under clinical supervision. Numerous people report feeling an instant sense of restoration after their very first session, with advancing advantages experienced over subsequent treatments.In conclusion, if you're seeking to improve your power levels, improve your well-being, and take an aggressive approach to your health, take into consideration integrating NAD infusion therapy into your wellness regimen. With its tested advantages for energy production, total health enhancement, ...

nad infusion