Deleting the S6K1 protein in mice reduces inflammation and extends lifespan by suppressing inflammatory proteins, highlighting a new mechanism in aging and potential treatments for age-related diseases.
S6K1 is a protein that plays a role in regulating aging and age-related diseases. Inhibiting this protein in mice has been shown to extend their lifespan and replicate the health benefits of calorie restriction, including lower body fat, stronger bones, and increased resistance to diabetes, although the exact mechanisms behind these effects were previously unclear.
S6K1 is a key target of the mTOR signaling pathway, which regulates growth and metabolism in response to nutrients and stress. The pathway also influences cellular senescence. As we age, senescent cells accumulate and release high levels of inflammatory proteins – a phenomenon known as the senescence-associated secretory phenotype (SASP).
Elucidating the relationship between S6K1, senescence, and the SASP will advance our understanding of aging and hold the potential for treating age-related diseases.
In research published today in Nature Aging, scientists at the LMS and the University of Tübingen have shown that deleting the S6K1 gene in aged mouse livers reduces inflammation by suppressing the production of inflammatory proteins released as part of the SASP, rather than by affecting senescence, as originally hypothesized by the research teams. Excitingly, this work now provides a biological mechanism for the beneficial effects of removing S6K1 upon aging and health span in mice first demonstrated by Professor Dominic Withers, Head of the Metabolic Signalling Group, and published in Science in 2009.
Uncovering converging pathways
While initially surprising, the findings corroborate those of other studies published this year, building an emerging picture of the interrelated role that inflammation, metabolism, and senescence play in aging and disease – all of which are strategic areas of research focus for the LMS.
This includes complementary work in fruit flies showing that the S6K protein controls inflammation, a study showing that simulating an excess of nutrients in mice increased inflammation and shortened lifespan, as well as work from Professor Stuart Cook, Head of the Cardiovascular Disease Mechanisms Group at the LMS showing that inhibiting an inflammatory protein, IL-11, led to health benefits and increased lifespan.
Now that the principles of S6K1 deletion have been established in liver tissue, the team plans to carry out follow-up studies to determine whether the same thing is happening in other tissues in the body.
Potential new strategies for treating age-related diseases
While inflammation plays an important role in helping your body respond to injury and infection, it is a significant driver of aging and many diseases. Enriching our knowledge of how inflammation contributes to aging and disease opens up avenues for developing new strategies to treat aging and age-related diseases.
Professor Withers, senior author, commented: “This work was a tour de force exploring the physiological, cellular, and molecular mechanisms that underlie the long-lived phenotype in mice lacking S6K1. It is becoming increasingly clear that inflammatory processes are a key component of age-related diseases and there is great potential for interventions that could modulate this process.”
Professor Jesús Gil, Head of the Senescence Group and senior author commented: “Enhancing our understanding of the interaction between metabolism, senescence and inflammation is a key first step to designing rational synergistic therapies that could be used to treat diseases of aging.”
Reference: “Ribosomal S6 kinase 1 regulates inflammaging via the senescence secretome” by Suchira Gallage, Elaine E. Irvine, Jose Efren Barragan Avila, Virinder Reen, Silvia M. A. Pedroni, Imanol Duran, Vikas Ranvir, Sanjay Khadayate, Joaquim Pombo, Sharon Brookes, Danijela Heide, Gopuraja Dharmalingham, Agharul I. Choudhury, Indrabahadur Singh, Nicolás Herranz, Santiago Vernia, Mathias Heikenwalder, Jesús Gil and Dominic J. Withers, 29 August 2024, Nature Aging.
DOI: 10.1038/s43587-024-00695-z
Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.
8 Comments
Very Interesting Research.
The Liver is the Chemical Factory which releases the enzymes and digestive Juices in the Digestive Tract . Have always wondered about Acidity and Acid Re-flux that we have All Experience some time during our life times.
For Digestion of Food that we consume we need these enzymes and digestive Juices with Ph levels levels in the Acidic Range to help digest the food (Starch) and convert to the sugars which supplies energy to our Cells and excess is stored as fat for storage in the Adipose Cells of the body for later use, in times of famine and scarcity, Camels do one better and store Water —-as the Ships of the Desert.
Now at meal times if the food does not arrive as per timetable these Enzymes and complex proteins like S6K1 protein cause Inflammation of the stomach lining as there is no food available to digest. Hence Antacids like Tums ( “Pop Pop , Fizz Fizz( , O what a Relief it is” provide relief to the Stomach as alkaline magnesium and Calcium carbonate Compounds are ingested and neutralize the Acidic S6K1 protein to some extent?
Health is a Personal Choice and governed by the Choices we make as far what we put into our mouths to consume.. As we grow older and the Bodies Cells Age our Digestive Abilities take a back seat and hence elderly prefer to eat more easily digestible foods , just like we feed babies when they start eating Solid foods after Mothers Milk has run Dry.
The food Choices we make determines our physical well being.
The thought choices we make determine our mental well being.
Prayers and surrender to the Almighty Creator , Preserver, Destroyer of Universes and Multiverse determines our Spiritual Well-Being.
The Choices we make determine our KARMIC Fate.
Personally I prefer to Change my Clothes daily and put the dirty ones for Wash. As the Bhaghwad Gita Reveals, All Mortals cast of their Older Bodies and take new ones as they traverse the Cycle of Birth , Death’ and Rebirth Cycle for eternity till they become one with the Almighty.
Can’t say if physical Immortality is a blessing or a curse. Deletion of the root cause of the Inflammation from the factory which produces same makes sense.
Views expressed are personal and not binding on anyone.
S6 kinase 1 is not involved in digestion.
Your irrelevant comment is an ill concealed “view” vehicle to promote your personal superstition.
Inflammation is driven by a number of factors, but primarily the consumption of dietary carbohydrates and the corresponding spike in glucose and insulin. In the total absence of carbohydrates in the diet, a non essential, nutrient, the body produces all the glucose it needs through the process of gluconeogenesis. At any one time the body only has 4g of glucose circulating in the blood stream which is plenty for all processes that need it. Any increase over that level is treated as a toxin that must be removed as quickly as possible by raising insulin and depositing as fat. The primary fuel for the body is fatty acids and ketones.
The PH of the body is tightly regulated. Acid reflux is a result of consuming carbohydrates which are fermentable, and require a higher PH to ferment in the digestive tract. The corresponding weakening of the acidity of digestion, and the corresponding gasses produced by fermentation in a digestive physiology that is not designed for fermentation, since humans are not herbivores with multiple fermentation chambers, leads to the experience of acid reflux. Removing carbohydrates from the digestive system will eliminate that issue in a mater of a few days. If you consume a proper human diet of only meat, this will not occur, and you will not loose your digestive ability as you age. Switching to “easily digestible baby foods” will not only further the digestive issues but will also lead to the muscle wasting of sarcopenia and accelerate aging. Feeding babies the so called “baby foods” after weaning is also a mistake as they need meat to chew to develop proper dentition and jaw structure. The practice of doing so is what has caused a combination of dental problems as well as improperly developed facial structures and breathing issues, such as mouth breathing in our modern society.
Regarding the entire longevity, gene manipulation, transhumanism push. It is a fools errand and stems from an inner recognition of the eternality of the human soul. We can try as hard as we can to extend our life, and pursue eternal life through hubristic human efforts, but it will eventually end in failure. The only way to eternal life is through our Lord and Savior Jesus Christ. He is the only way, the Truth and the life, and no one comes to the father except through him. Repent of your sins and put your faith in him, for he died on the cross for our sins, and rose in three days. Our salvation is through faith alone in Christ.
Well Said,,,Amen
S6 kinase 1 is not involved in pH regulation.
Your irrelevant comment is an ill concealed “view” vehicle to promote your personal superstition.
Thank you. I’m glad you are a great witness. Almighty and wonderful is our Heavenly Father. His will done forever and ever. In Jesus Christ Mighty name.
It’s that time of the year again when members of organized superstition spam science sites. Three comments, none relevant to the mTOR/S6K1 signaling pathway discoveries.
Have they asked what is it that the body thinks is a pathogen ? What is it that the body thinks it needs to react to ? The reaction results in inflammation.
Is there a microorganism resident in the body that releases something that the body is reacting to, or have the cells that produce detector cells been damaged and are producing defective detector cells ? Or do the cells responsible for the walls of our digestive tract fail to keep pace ?