Researchers Solve Anti-aging Mystery – Identify Gene Responsible for Cellular Aging

Reverse Aging

Cellular reprogramming can reverse aging in mesenchymal stem/stromal cells (MSCs). A new study reveals the molecular mechanisms behind this, shedding light on MSC aging and potential pharmacological strategies to combat it.

Cellular reprogramming can reverse the aging that leads to a decline in the activities and functions of mesenchymal stem/stromal cells (MSCs). This is something that scientists have known for a while. But what they had not figured out is which molecular mechanisms are responsible for this reversal. A study released today in STEM CELLS appears to have solved this mystery. It not only enhances the knowledge of MSC aging and associated diseases, but also provides insight into developing pharmacological strategies to reduce or reverse the aging process.

The research team, made up of scientists at the University of Wisconsin-Madison, relied on cellular reprogramming — a commonly used approach to reverse cell aging — to establish a genetically identical young and old cell model for this study. “While agreeing with previous findings in MSC rejuvenation by cellular reprogramming, our study goes further to provide insight into how reprogrammed MSCs are regulated molecularly to ameliorate the cellular hallmarks of aging,” explained lead investigator, Wan-Ju Li, Ph.D., a faculty member in the Department of Orthopedics and Rehabilitation and the Department of Biomedical Engineering.

Mesenchymal Stem/Stromal Cells

When mesenchymal stem/stromal cells (MSCs) age, the transcription factor GATA6 is increasingly produced in the cell to induce aging response. By transcription factor-based cellular reprogramming, aged MSCs are rejuvenated with a reduction in GATA6 effects on cellular aging. Credit: AlphaMed Press

The researchers began by deriving MSCs from human synovial fluid (SF-MSCs) — that is, the fluid found in the knee, elbow and other joints — and reprogramming them into induced pluripotent stem cells (iPSCs). Then they reverted these iPSCs back to MSCs, in effect rejuvenating the MSCs. “When we compared the reprogrammed MSCs to the non-rejuvenated parental MSCs, we found that aging-related activities were greatly reduced in reprogrammed MSCs compared to those in their parental lines. This indicates a reversal of cell aging,” Dr. Li said.

The team next conducted an analysis of the cells to determine if there were any changes in global gene expression resulting from the reprogramming. They found that the expression of GATA6, a protein that plays an important role in gut, lung and heart development, was repressed in the reprogrammed cells compared to the control cells. This repression led to an increase in the activity of a protein essential to embryonic development called sonic hedgehog (SHH) as well as the expression level of yet another protein, FOXP1, necessary for proper development of the brain, heart, and lungs. “Thus, we identified the GATA6/SHH/FOXP1 pathway as a key mechanism that regulates MSC aging and rejuvenation,” Dr. Li said.

“Identification of the GATA6/SHH/FOXP1 pathway in controlling the aging of MSCs is a very important accomplishment.” Said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. “Premature aging can thwart the ability to expand these promising cells while maintaining function for clinical use, and enhanced knowledge about the pathways that control differentiation and senescence is highly valuable.”

To determine which of the Yamanaka transcription factors (four reprogramming genes used to derive iPSCs) were involved in repressing GATA6 in the iPSCs, the team analyzed GATA6 expression in response to the knockdown of each factor. This yielded the information that only OCT4 and KLF4 are able to regulate GATA6 activity, a finding consistent with that of several previous studies.

“Overall, we were able to demonstrate that SF-MSCs undergo substantial changes in properties and functions as a result of cellular reprogramming. These changes in iPSC-MSCs collectively indicate amelioration of cell aging. Most significantly, we were able to identify the GATA6/SHH/FOXP1 signaling pathway as an underlying mechanism that controls cell aging-related activities,” Dr. Li said.

“We believe our findings will help improve the understanding of MSC aging and its significance in regenerative medicine,” he concluded.

Reference: “GATA6 regulates aging of human mesenchymal stem/stromal cells” by Hongli Jiao, Brian E. Walczak, Ming‐Song Lee, Madeleine E. Lemieux and Wan‐Ju Li, 30 November 2020, STEM CELLS.
DOI: 10.1002/stem.3297

16 Comments on "Researchers Solve Anti-aging Mystery – Identify Gene Responsible for Cellular Aging"

    Folks, proteins are the building molecules of all cells on Earth of all species. The brain is a mass that is better at doing things than a The brain is nature’s greatest creation. The stomach is a processing apparatus that converts what you ate into you. Feed your body food that contains all the 9 essential amino acids that a human body needs for proper development and that very smart brain of yours will assemble many kinds of proteins that your body needs without any conscience input from you. Your brain does all that work without any conscience input from you all your life and do a very good job at it as long as you give your body those 9 essential amino acids people get from eating food. Beans are natures gift to the human race because beans contain most if not all of the nutrients people need to have healthy bodies. Beans contain massive amounts of complete proteins that have the 9 essential amino acids. I came up with a recipe I called Adelynn’s Miracle Beans recipe and diet plan. I lived on this bean recipe for about 5 years from age 62 to 67 years old because I was broke and needed a low cost way of eating. I mostly ate that bean recipe for those 5 years and in that time I felt my body transform before my eyes! My skin became smoother as my wrinkles went away and at 62 years old my skin turned into looking the youngest my skin ever looked in 40 years. My muscles got the strongest they ever were in my life! My E.D. problems went away and my stiffy got the hardest it ever was in my life and here I was in my 60’s! I would wake up at night with stiffy sticking up hard as a rock! Girls will love guys who eat this Adelynn’s Miracle Beans! Why it could put Viagra out of business I always say! Also My weight problem completely disappeared without effort as my body turned into a 10 and before that I was overweight and out of shape! Adelynn’s Miracle Beans works well to regulate your body correctly because it empties out your stomach and replaces it with a bean recipe that contains all the 9 essential amino acids to make perfect cells of every kind and that is just what your body will do as long as you are feeding it Adelynn’s Miracle Beans. What makes Adelynn’s Miracle Beans work so well is the fact that this bean recipe has these 9 essential amino acids. However it also is a recipe that contains massive amounts of fiber. It will empty our your stomach, get rid of your pot belly, clean out your digestive system and get up and running in your body a cell building process that will make perfect cells of all kinds. This is a great recipe for relieving constipation. It will surely make you poop! As months go on after you start eating this bean recipe you will see a new better looking and healthier body. Every 3 months you will see notable changes. After a year of eating the bean recipe and following the diet plan you will see a whole new you! I call this recipe I created called Adelynn’s Miracle Beans the Fountain Of Youth recipe because that is what it did for me! Adelynn’s Miracle Beans recipe and diet plan made a younger man out of this old man! Adelynn’s Miracle Beans is posted on the internet.You don’t have to make Adelynn’s Miracle Beans with the 12 different kinds of beans. You probably could cut that down to about 4-7 different kinds of beans and MAYBE get the same results. The reason I say that is because ever since I stopped eating the full recipe of 12 different kinds of Adelynn’s Miracle Beans and instead now eat a bean recipe with only 2-3 different kinds of beans I find that my body still create a better body of mine in many ways still but not as good as times when I ate the 12 different bean recipe. You are going to have to experiment with what and how many different beans to put into your bean recipe. Read my posting of Adelynn’s Miracle Beans to read about all the wonders that it can do for your body. Just be careful because you may have to cut down on the bean mixture a little because of the massive amount of fiber in it. I didn’t mess with the recipe to find the different results from different bean mixes. Also I will say to all of you that Adelynn’s Miracle Bean recipe is a very very low cost and very very highly nutritional recipe that can easily feed people in these rough times we are in!

  2. The condition of one’s collagen fiber matrix determines how youthful you look. There are ways to work on yours that the medical industry doesn’t understand or isn’t saying.

    • Torbjörn Larsson | December 1, 2020 at 12:52 pm | Reply

      Because in conspiracy ideation they don’t want to help and earn money.

      In real life, however, most people do.

    • No, there is a lot more, and elastin is at least as important. No one talks about it because adults can make elastin. Puberty ends it. What you’ve got, is what you’ve got, and it is being constantly damaged. Rubber bands don’t last in the sunshine.

  3. Both Comments above are very interesting.

    The aspiration for permanent youthful looks is a dream for many, especially the female gender in the human species,who use articial dyesto keep the hair dark or Botox to keep the face looking youthful! Even among the Apes as er research Conducted by a great lady scientist in the Congo who has been bestowed the title of Dame, in recent times.

    Looks like baby steps have started emerging on the road to physical immortality. However, we need to be careful as the mental impact of such “Immortality” may be disastrous and have unintended consequences. The Unitended Consequences of such permanent youth and rversal of physical aging may create youthful looking humans but the mental maturity not aligned with the reality of the physical appearance. Wonder how this is related to the Telomer research I was reading about some time back.

    Opinions expressed are Personal.

  4. What we don’t need is aged old rejuvenated grannies seducing young men.

  5. What we really need is to cure death because everyone is valuable and I want to see us all able to choose to either be friends or otherwise have a nice life in harmony, joy, celebration, art, free choice, sobriety, craft, thought, inquisitiveness, and many other unique traits to us and our ancestors which all worked together to bring us here. With nothing lost, and only everything recovered, we redeem all the prayers and dreams that always pointed forward, towards us and beyond.
    We’ll always argue, and no framework can fit every passion, but the exploration of each passion is always negotiable and there’s certainly a way to help everyone to be as lucidly/genuinely/understandingly/truly/fittingly celebratory as can be.

    • Torbjörn Larsson | December 1, 2020 at 12:55 pm | Reply

      Evolution is the basic process of biology and it happens in populations over generations. Without death, no life.

      • Populations can grow without bounds, or without meaningful bounds. Plenty of room in the solar system for many trillions of humans. And we will probably be able to spread to other systems before we fill this one.
        No need for aging death.

  6. What is where are these miracle ECM molecules you speak of?

  7. Leroy A Rodgers | August 25, 2021 at 8:30 am | Reply

    Where do I sign up

  8. There’s been a ton of new anti aging research even since 2020! There are now at least 15 different anti-aging scientific journals out there:

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