LONGECITY

This idea sprung up in a discussion about some recent research where the removal of senescent cells improve the aging biomarkers of genetically altered mice.

It seems there are many questions about senescent cells. Our members are very curious about this recent research result and would like to find out what possible methods are available for removing senescent cells, or countering the pro-aging effects of these cells.

Does anyone know of a current database of information on senescent cells? Is there a dearth of knowledge on this subject? If so, would a literature review of senescent cells be a good project for Longecity to support. Some members have already shown interest in financially supporting something like this.

I would suggest a full literature review and the creation of a detailed wiki on senescent cells, their affects on aging, and possible techniques for removal from humans.

I suggest that this be a part of Longecity's science initiative, or perhaps we could fund someone from the SENS academic initiative.

Critiques please.
Edited by Mind, 09 November 2011 - 09:52 PM.

There are a number of publications and reviews on this topic already. I suspect even more will be emerging following the highly popularized results of the recent Mayo Clinic study. If you're looking to develop an information storage for your member base that seems like an interesting project, but in terms of a publication grade document for a peer-reviewed journal, those are already available.

Thanks Kelsi. I see Michael also wrote an extensive report here.

Just wondering if there is anything Longecity could add or help out with (besides just generically throwing money around to different organizations). Perhaps there are other aspects of aging (and the SENS 7) that could better use this type of effort. I do not have enough knowledge to determine.

Great suggestion Mind. The most important thing now is that this research gets replicated in normal mice. Maybe we should contact the authors and check if they are planning to do this. The cost of such a study is beyond what we can do. However, the method used would not be applicable to humans (they inserted a genetic construct that causes the cells to commit suicide when they become senescent), thus LongeCity might be able to help by funding research aimed at developping a method that is applicable to humans. For this to happen we need better insight in the molecular mechanisms of senescence. Maybe we can fund a bioinformatics study on gene expression changes in senescent cells (I don't know to what extend this has already been researched). Based on these data researchers would then be able to identify a pathway that we can interupt in senescent cells leading to their death. For LongeCity it would be a good idea to have a science article on senescent cells (I will look into this).

Another important discovery published last week was a way to make young iPS stem cells from old donors. This is very important for cell therapy because you don't want to get treated with old cells. We should commission a science article about iPS stem cells too.

I also think this a great idea.

Maybe an even broader scope would be possible? For instance a wiki that takes the SENS 7 deadly things as main index for organising information regarding related research. Otherwise we might end up with a bunch of articles that only reflect actuality, but lack a certain conceptual overview that SENS could provide.

This would be a more long term approach and hence would require a high level of endurance. Maybe this could be done in cooperation between imminst and heales?

Kelsi says everything is already known about this subject. I doubt it. There has to be some way Longecity can accelerate the development of this type of rejuvenation and/or find out if it is possible in humans.

Maybe I did misunderstand your idea Mind. I was referring more to an overview of existing research information. That could be an incentive for attraction of funding as well?

You understand just find. By contributing some time/money to organize (and discover) what is known about senescent cells and their removal, we should be able to accelerate this potential avenue for rejuvenation.

Kelsi says everything is already known about this subject. I doubt it. There has to be some way Longecity can accelerate the development of this type of rejuvenation and/or find out if it is possible in humans.

No, Kelsey said that reviews have already been written, he did not say that everything is already known. What he meant is that it wouldn't be like with glucosepane. Nobody had brought together the glucosepane research in an overview. But constantly new research is published and thus the need for new summaries continues to exist.

Campisi J. Cellular senescence: putting the paradoxes in perspective. Curr Opin Genet Dev, 2011, 21(1): 107-112.

Rodiers F, Campisi J. Four faces of cellular senescence. J Cell Biol, 2011, 192(4): 547-56.


Coppé JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol, 2010, 5:99-118.


Davalos AR, Coppe JP, Campisi J, Desprez PY. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev, 2010, 29(2): 273-283.


Ren JL, Pan JS, Lu YP, Sun P, Han J. Inflammatory signaling and cellular senescence. Cell Signal, 2009, 21(3): 378-383.

Adams PD. Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence. Mol Cell, 2009, 36(1): 2-14.

Kelsi says everything is already known about this subject. I doubt it. There has to be some way Longecity can accelerate the development of this type of rejuvenation and/or find out if it is possible in humans.

No, Kelsey said that reviews have already been written, he did not say that everything is already known. What he meant is that it wouldn't be like with glucosepane. Nobody had brought together the glucosepane research in an overview. But constantly new research is published and thus the need for new summaries continues to exist.

Campisi J. Cellular senescence: putting the paradoxes in perspective. Curr Opin Genet Dev, 2011, 21(1): 107-112.

Rodiers F, Campisi J. Four faces of cellular senescence. J Cell Biol, 2011, 192(4): 547-56.


Coppé JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol, 2010, 5:99-118.


Davalos AR, Coppe JP, Campisi J, Desprez PY. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev, 2010, 29(2): 273-283.


Ren JL, Pan JS, Lu YP, Sun P, Han J. Inflammatory signaling and cellular senescence. Cell Signal, 2009, 21(3): 378-383.

Adams PD. Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence. Mol Cell, 2009, 36(1): 2-14.

So what needs to be known in order to move this avenue of research into human trials? What is the next step?

what needs to be known in order to move this avenue of research into human trials? What is the next step?

Here is IMO the path to humans:
1- remove senescent cells in normally-long-lived mice, through genetic trick
2- test it on some disease in mice (like http://www.ncbi.nlm....pubmed/21886162 did with young plasma injections, for cognitive functions)
3- test it also on lifespan

1'- remove senescent cells in normal mice in a way that does not require genetic trick
2'- testing it on old mouse cognitive function
3'- testing it on cognitive function in humans

(1') should not be forgotten!

Perhaps people from LongeCity could ask the researchers how they would do that (1'), who is planning to do what, report it in the member section, and then we'd have the basis to decide how it can help.
Edited by AgeVivo, 13 November 2011 - 02:09 PM.

We could aim an upcoming fundraiser at a project in this area and collect applications.

A literature review to post on Longecity sounds great. We could spread that link instead of from other sources.

If Sven can get them to write an article that would be amazing. Somebody else in the field would be good too it seems.

Im interested to know where this might all be lined up centrally. I would like to see a list of the 7 known forms of damage, 7 columns, with links to all the various past, present and proposed research in the area. Same thing with other strategies. I see that as one of the main jobs of our science initiative, if it isnt already being done elsewhere.

I wonder if cell surface bound IL-1α could be a target? Perhaps a non-neutralizing IL-1α antibody could be used to tag senescent cells for elimination.
http://freepdfhostin.../d77cd2cd37.pdf
http://jcb.rupress.o...47.figures-only
Edited by revenant, 03 December 2011 - 10:13 PM.

We could aim an upcoming fundraiser at a project in this area and collect applications.

A literature review to post on Longecity sounds great. We could spread that link instead of from other sources.

Yes. Ideas for project as well as litterature investigation are going very fast on this thread:
http://www.longecity...ng/page__st__60