4 replies to this topic

[alc]

Embryonic gene Nanog reverses aging in adult stem cells


http://www.buffalo.e...016/07/023.html


and


NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression

http://onlinelibrary...17DAF0D3.f02t02

"

Abstract

Cellular senescence as a result of organismal aging or progeroid diseases leads to stem cell pool exhaustion hindering tissue regeneration and contributing to the progression of age related disorders. Here we discovered that ectopic expression of the pluripotent factor NANOG in senescent or progeroid myogenic progenitors reversed cellular aging and restored completely the ability to generate contractile force. To elicit its effects, NANOG enabled reactivation of the ROCK and Transforming Growth Factor (TGF)-β pathways—both of which were impaired in senescent cells—leading to ACTIN polymerization, MRTF-A translocation into the nucleus and serum response factor (SRF)-dependent myogenic gene expression. Collectively our data reveal that cellular senescence can be reversed and provide a novel strategy to regain the lost function of aged stem cells without reprogramming to the pluripotent state.

"

[Nate-2004]

Another related article: http://newatlas.com/...se-aging/44544/

[Turnbuckle]

Lithium is known to stimulate Nanog and also increase longevity in humans--

 

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors. The low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limited the potential application of iPSCs. Here we report that Lithium (Li), a drug used to treat mood disorders, greatly enhances iPSC generation from both mouse embryonic fibroblast and human umbilical vein endothelial cells. Li facilitates iPSC generation with one (Oct4) or two factors (OS or OK). The effect of Li on promoting reprogramming only partially depends on its major target GSK3β. Unlike other GSK3β inhibitors, Li not only increases the expression of Nanog, but also enhances the transcriptional activity of Nanog. We also found that Li exerts its effect by promoting epigenetic modifications via downregulation of LSD1, a H3K4-specific histone demethylase. 

 

http://www.ncbi.nlm....les/PMC3193456/

 

 

 

Edited by Turnbuckle, 05 August 2016 - 10:34 AM.

[Nate-2004]

Thing is though I've known people who had taken lithium for years and they are definitely not younger or staying the same age, my father being one of them.

[Turnbuckle]

Thing is though I've known people who had taken lithium for years and they are definitely not younger or staying the same age, my father being one of them.

 

From their data it looks like the in vitro effect is very sensitive to the LiCl concentration. Too much and you get less than the control. See Fig. 1B and Fig. 1I, where the effect peaks at 10 mM and plunges to zero at 40 mM. However the usual treatment dose for manic depression is much less than the peak. From another paper--

 

 

The effective dose range for lithium is 0.6-1.0 mM in serum and >1.5 mM may be toxic.

http://www.ncbi.nlm....pubmed/19523343

 

 

So something else will be needed. For instance, the paper in my previous post says that LiCl has a synergistic effect with Vc and VPA (vitamin C and valproic acid)--

 

Next we tested LiCl in combination with two reported reprogramming enhancers, VPA and Vc. The combination of LiCl and VPA displayed an additive effect (Figure 1G), suggesting that they act through different mechanisms. As the KSR supplement already contains Vc and additional Vc did not add effect to the overall reprogramming efficiency (11 and our own observation), the combination of LiCl and Vc were tested in mES medium supplemented with FBS. The reprogramming process was much slower and efficiency was much lower in mES medium compared to KSR medium. At day 12, both Vc and LiCl showed marginal effect in enhancing reprogramming on their own. To our surprise, the combination of two displayed a robust synergistic effect (Figure 1H), suggesting crosstalk of pathways or targets regulated by these two small molecules... 

 

Our data also indicates a synergistic effect of Li and Vc and the mechanism also remains to be elucidated. It is also interesting that Li, Vc and VPA have all been reported to have anti-aging effect, and all three have such potent effect on reprogramming.

 

http://www.ncbi.nlm....les/PMC3193456/

 

Edited by Turnbuckle, 05 August 2016 - 03:43 PM.