Another possibility for antiaging drugs for removing senescent cells

by

The University of Exeter has new compounds which reduced the number of senescent cells (older cells that have deteriorated and stopped dividing) up to 50%.

The Exeter team also identified two splicing factors (a component of cells) that play a key role in when and how endothelial cells become senescent. The findings raise the possibility of future treatments not only for blood vessels – which become stiffer as they age, raising the risk of problems including heart attacks and strokes – but also for other cells.

Researchers tested three different compounds, all developed at the University of Exeter, and found each produced a 40-50% drop in the number of senescent blood vessel cells.

The compounds in question – AP39, AP123 and RT01 – have been designed by the Exeter team to selectively deliver minute quantities of the gas hydrogen sulfide to the mitochondria in cells and help the old or damaged cells to generate the ‘energy’ needed for survival and to reduce senescence.

Aging Journal – Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2.

Cellular senescence is a key driver of aging, influenced by age-related changes to the regulation of alternative splicing. Hydrogen sulfide (H2S) has similarly been described to influence senescence, but the pathways by which it accomplishes this are unclear. We assessed the effects of the slow release H2S donor Na-GYY4137 (100 µg/ml), and three novel mitochondria-targeted H2S donors AP39, AP123 and RT01 (10 ng/ml) on splicing factor expression, cell proliferation, apoptosis, DNA replication, DNA damage, telomere length and senescence-related secretory complex (SASP) expression in senescent primary human endothelial cells. All H2S donors produced up to a 50% drop in senescent cell load assessed at the biochemical and molecular level. Some changes were noted in the composition of senescence-related secretory complex (SASP); IL8 levels increased by 24% but proliferation was not re-established in the culture as a whole. Telomere length, apoptotic index and the extent of DNA damage were unaffected. Differential effects on splicing factor expression were observed depending on the intracellular targeting of the H2S donors. Na-GYY4137 produced a general 1.9 – 3.2-fold upregulation of splicing factor expression, whereas the mitochondria-targeted donors produced a specific 2.5 and 3.1-fold upregulation of SRSF2 and HNRNPD splicing factors only. Knockdown of SRSF2 or HNRNPD genes in treated cells rendered the cells non-responsive to H2S, and increased levels of senescence by up to 25% in untreated cells. Our data suggest that SRSF2 and HNRNPD may be implicated in endothelial cell senescence, and can be targeted by exogenous H2S. These molecules may have potential as moderators of splicing factor expression and senescence phenotypes.

Oisin Biotechnology

Oisin Biotechnologies seems to be ahead of the University of Exeter as their senescent cell clearing is over 80% and has been tested for over 7 months on mice and for months on monkeys.

21 thoughts on “Another possibility for antiaging drugs for removing senescent cells”

  3. If “coed” is short for “co-educational”, which means men and women attending the same establishment (gasp!) then doesn’t that make both the men AND the women “coeds”? One of those American words that don’t make sense to the rest of us.

  4. If coed”” is short for “”””co-educational”””””””” which means men and women attending the same establishment (gasp!) then doesn’t that make both the men AND the women “”””coeds””””?One of those American words that don’t make sense to the rest of us.”””

  7. proliferation was not re-established in the culture as a whole” I took that to mean that while the cells returned to functioning, they didn’t return to growth and division.

  8. proliferation was not re-established in the culture as a whole”” I took that to mean that while the cells returned to functioning”””” they didn’t return to growth and division.”””

  9. So, upside is you get yourself a sugar mamma, downside is you don’t get to sleep with a college girl any more.

  10. So upside is you get yourself a sugar mamma downside is you don’t get to sleep with a college girl any more.

  11. Jeret, Be aware that vuukle disapproves of evidence and citations. So any attempt to put a link in a post results in a meaningless half statement like you just posted. Give the plain name of where someone should go, so they can google it up and find it themselves. And give enough keywords that they aren’t left looking through 20 000 hits.

  12. JeretBe aware that vuukle disapproves of evidence and citations. So any attempt to put a link in a post results in a meaningless half statement like you just posted.Give the plain name of where someone should go so they can google it up and find it themselves. And give enough keywords that they aren’t left looking through 20 000 hits.

  14. If “coed” is short for “co-educational”, which means men and women attending the same establishment (gasp!) then doesn’t that make both the men AND the women “coeds”?

    One of those American words that don’t make sense to the rest of us.

  16. “proliferation was not re-established in the culture as a whole”
    I took that to mean that while the cells returned to functioning, they didn’t return to growth and division.

  18. Jeret,
    Be aware that vuukle disapproves of evidence and citations. So any attempt to put a link in a post results in a meaningless half statement like you just posted.
    Give the plain name of where someone should go, so they can google it up and find it themselves. And give enough keywords that they aren’t left looking through 20 000 hits.

  20. I’ve tried periodic high dose Quercetin, and noted that some of my more troubling aged spots on my skin became inflamed, and then came back better looking. But the recent research into it doesn’t look good, so I’ve been debating whether to resume using it. I had to lay off experimenting with supplements this last year, (Except for the SAMe, without which I’d barely be mobile!) due to the cost of putting my wife through college.

    But she’s graduated and starts work next week, so I should be able to resume supplementation. Time to review the literature and figure out what I should be taking.

  21. If I’m reading this correctly, they’re recovering cells from senescence rather than culling them. This raises a few questions, like, do we even want these cells to divide? Do they have poorly functioning mitochondria that their daughter cells will inherit, and other problems? On the other hand, strategies that focus on inducing apoptosis in senescent cells may not be safe all at once, given the rather extreme numbers of senescent cells the elderly can rack up. So maybe a combo strategy would be worthwhile. Recover what cells you can, kill the rest, later come back and kill some more.

Comments are closed.