Genes for Regulating Stem Cell Aging Identified

The exact gene that caused stem cell aging has been identified.

Above – 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

University of Wisconsin-Madison researchers 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 lung. “Thus, we identified the GATA6/SHH/FOXP1 pathway as a key mechanism that regulates MSC aging and rejuvenation,” Dr. Li said.

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.

SOURCES- UW-Madison, Stem Cell Journal
Written By Brian Wang,

8 thoughts on “Genes for Regulating Stem Cell Aging Identified”

  1. The development of senolytics does precisely this. They course through the body clearing out senesent cells. A number of these are already in use, such as Dasatinib…

  2. Parthenogenetic animals and critters reproducing by budding and/or mitosis have also fared quite well for millions of years.

    The process of rejuvenation and production of young and clean cell lines coming from an old organism is a fact.

    We just need to understand the trick and apply it to living cells, while removing the damaged ones. Easier said than done, though.

  3. But DNA can be repaired and maintained and this is done on a routine basis. The human race, collectively with our non-human ancestors, has been maintaining viable DNA for around four billion years.

    A human is just a zygote's way of making more germ cells, that can then create more gametes, so the gametes can make more zygotes.*

    To put it another way, germ cells are highly specialized cells that make gametes. Germ cells are the only cells within an organism that contribute genes to offspring (all the other cells are somatic cells). A species can only continue if the DNA in germ cells is kept almost perfectly intact. This strongly indicates that germ cells can protect and repair their genetic information indefinitely. It is a kind of immortality.

    Somatic cells don't get this level of protection, probably because it is expensive and they don't need it to survive long enough for the germ cells to create gametes that combine with other gametes to create zygotes that then become humans that can produce more germ cells, gametes, and zygotes.

    So somatic cells are not designed to outlive their warranty period . . . yet we are the somatic cells! As individuals, we want somatic cells to be repaired. We want the germ cell secret. Even if It might be very expensive (among other things, it almost certainly will reduce fecundity) it might still be a price we are able and willing to pay.

    *With apologies to Robert Heinlein.

  4. Interesting as this is, "aging" is also classified as a buildup of damage to DNA due to external factors and isn't as easily reversed as we'd like to think. I think doing that would require healing at an internal level of which we aren't yet capable. One day, though.

    This is curious though, because it could possibly be used to slow the process of aging in some internal systems. Or is that wrong?

  5. We evolve to get old and die so our children will have food. Or something along those lines. No reason the *ability* to change this is not already programmed in as options already developed in the past (live longer). Epigenetic control of development as well as epigentic response to environment provide vast capabilities for life adaption and *evolution* without the drastic "mutations", just selecting from stuff that used to work in the past. Now, these guys were knocking out stuff for research, so this is not itself a treatment.

  6. "the expression of GATA6, . . ., was repressed in the reprogrammed cells". This is epigenetics at work, like Janov has been doing/changing for years.

  7. I think we need to be more precise when saying something is 'aging'.
    Are we simply talking about:
    – time passing (poor, never use this)
    – a statistical thing, such as 'everyone's learning ability deteriorates with time passing' (weak, avoid this)
    – a component or process deteriorating/ subject to errors in its 'intended' process/ service life, such as cells becoming senescent
    – a component being used up, such as with the thymus
    – a component affected in its service based on 'timed functions' – puberty, menopause
    – a component that deteriorates due to overuse, misuse, lack of easy maintenance; but is more prevalent due to extended period of 'neglect', such as being overweight.
    To me aging effects really only count if you have otherwise done everything possible to stay healthy.

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