Hi,

This question has been posed and answered by many groups. If you are talking about cells in a dish, the answer is definitely yes. Many cell types (not all) can be made immortal by ectopic expression of hTERT alone. Many people have done this on various cell types. Many, but not all cell types in culture can be immortalised by hTERT alone. These cells exhibit normal characteristics and are not transformed (do not grow in soft agar or form tumours in nude mice). Although they are immortal, they still undergo the process of ageing as measured by the epigenetic changes to their genome (epigenetic clock).

If you are asking about making cells in a body immortal, then clearly this has not been done and I doubt will ever be done due to the huge uncertainty of the effect of ectopic expression of hTERT. In any case, it is perhaps not such a bad thing that we do not live forever.

Hope this helps.

Ken

Hello,

According to me it is not possible to modify mortal cells to immortal cells without making them cancerous, As most immortal cell lines are cancer cell lines or embryonic stem cell lines.  However, we can control aging by avoiding a telomere crisis by administration  of  stem cells mostly mesenchymal stem cells.

I have no idea about this..... but it seems to be a very important question.... keep searching!!! You wonderful person! 

I do not think that such a way could be effective. We proposed another way for the celllular life prolongation (see: Ostrovskii V.E., Kadyshevich E.A., Optimal nutrition and cellular life prolongation in the LOH-Theory content", Book "Safe food", Novi Sad, Serbia, 2014, pp 293-299; the paper is available at the ResearchGate site, see my ResearchGate pages).

There are numerous human stem cell populations that exhibit telomere shortening despite expressing telomerase, albeit at low levels (HSCs, intenstinal crypts, probably others). There's more to telomere maintenance than just expressing telomerase. The telomerase needs to be able to get to the telomeres, which are normally protected by the shelterin complex. Moreover, the telomeres undergo post-replication processing to specify the 3' and 5' end sequences, which also likely affects telomerase recruitment and shelterin binding. Finally, the catalytic activity of telomerase and the maturation of the telomerase holoenzyme is affected by many proteins in vivo. It's complicated.

The question of whether simply expressing more telomerase could overcome telomere shortening has been examined genetically, and remains contentious. Maria Blasco claims that Adenovirally delivered TERT can increase the mouse lifespan, without significantly increasing cancer rates (though I doubt she had the statistical power to reliably detect such an increase). DePinho's also done work on this topic, albeit in more-complicated scenario's than Blasco (e.g. in TERT KO mice). While it occasionally looks like TERT can do good things for cells, it also appears to promote the progression (though perhaps not the occurrence) of cancer. Ubiquitously and unconditionally expressing telomerase in vivo in mammals looks too dangerous. Blasco did test it in mice bearing additional copies of some tumor suppressors a while back (http://www.sciencedirect.com/science/article/pii/S0092867408011914).

I have my own pet ideas about how to mitigate some of these risks, but am not working in a lab that is interested in pursing this project.

@Dear Seema> exactly this is the point. I am wondering to know if we can do this work without arriving to the cancerous cells and healthy cells with immortal feature!!!

@Dear Charlene> Thanks for your kind attention.

@Dear Victor> I will read these references. thanks

@Dear Brian> Thank you so much for your detail. I will read more about these references and works which you pointed. 

Hi,

This question has been posed and answered by many groups. If you are talking about cells in a dish, the answer is definitely yes. Many cell types (not all) can be made immortal by ectopic expression of hTERT alone. Many people have done this on various cell types. Many, but not all cell types in culture can be immortalised by hTERT alone. These cells exhibit normal characteristics and are not transformed (do not grow in soft agar or form tumours in nude mice). Although they are immortal, they still undergo the process of ageing as measured by the epigenetic changes to their genome (epigenetic clock).

If you are asking about making cells in a body immortal, then clearly this has not been done and I doubt will ever be done due to the huge uncertainty of the effect of ectopic expression of hTERT. In any case, it is perhaps not such a bad thing that we do not live forever.

Hope this helps.

Ken

Hello Sir,

The question is to make cell immortal so that it is possible to avoid aging. This is very critical to determine when a proliferative cell population became cancerous. If U could able know that then u can create wonder. this is a complete balance between self renewal activity and proliferation and after achievement of optimum then addition of antiproliferative agent.

Cell division its differentiation and apoptosis are delicately balanced in every tissue. Nobody knows where is the Master clock but definitely there are hundreds of different factors which govern such complicated process. So if we disturb the balance between cell division, differentiation and apoptosis ( which certainly is required to delay senescence) it can create havoc in the system atleast in the invivo situation.

Dear Seema and Arash,

The potential contributory role of telomere length in aging in organisms has been sometimes debated. In adults of long–lived seabirds, telomere length in blood cells is not related to age. It has been indicated that the loss of telomere is probably not constant with age. Attrition of telomere as a variable in longevity has been reported to be confounded by body size.

It has been documented that primary melanomas, in spite of growing well, eventually arrested. It was shown that immortality is potentially only a feature of later-stage disease that is more likely to spread.

Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123747/

http://scienceblog.cancerresearchuk.org/2011/04/21/new-results-cast-doubt-on-cancers-immortality/

New results cast doubt on cancer’s immortality (Cancer Research UK).

“But Professor Bennett realised that nobody had ever actually proved the existence of ‘immortal’ cells in early-stage cancers, which haven’t yet acquired the ability to spread.”  

I'd add to the former answers that attempting to render somatic cells immortal would mean putting some kind of "regression" of complexity upon them (towards simpler forms of life) : very risky and anti-evolutive ! 

To Ken, Seema, Brian, Chithan, Guibert ...

One key limitation regarding many important biological issues, including the cancer/age, is the gene-centric thinking.  However, these issues need the answer from bio-systems point of view rather than a specific “magic” part, such as TERT.  In many artificial systems, we can prove our point, as many of you have mentioned.  However, the real life is not about the artificial systems we (scientists) created.  Sorry!

To illustrate this point, we have discussed the “parts of gene vs. genome system”, using cancer as an example.  See:

“Evolutionary mechanism unifies the hallmark of cancer”

http://www.ncbi.nlm.nih.gov/pubmed/24957955

To me, life is an evolutionary package with trade-offs.  We just cannot put too much “wishful thinking” into our favor pathways.  The challenge for many molecular researchers is to appreciate and understand evolution.  We know too much molecular information but the life.  Please see the evolutionary trade-off story about the cancer:

“Stress, genomic adaptation, and the evolutionary trade-off”

http://www.ncbi.nlm.nih.gov/pubmed/24795754

For those who want deeper analysis, please go to my new book:  Debating Cancer:  The Paradox in Cancer Research.   

http://www.worldscientific.com/worldscibooks/10.1142/8879

Thanks, and keep searching!

http://www.worldscientific.com/worldscibooks/10.1142/8879#t=toc