June 08, 2014
Genes For Long Telomeres Boost Brain Cancer Risk

Every time Icome across a report of some gene, protein, or hormone that is claimed to have the potential to make us live longer I am always very skeptical. Our bodies wear out and any effort to turn up the knob on activity in a type of cell or organ risks turning up the risk of cancer or some other disease that strikes when worn out cells are made to do more than they safely can do. This latest report provides an example. As the telomere caps on chromosomes wear down cells lose the ability to divide. So longer telomere caps good? Shorter telomere caps bad? Not that easy. Cells that can divide more times are cells that gain more chances to go cancerous.

New genomic research led by UC San Francisco scientists reveals that two common gene variants that lead to longer telomeres, the caps on chromosome ends thought by many scientists to confer health by protecting cells from aging, also significantly increase the risk of developing the deadly brain cancers known as gliomas.

The genetic variants, in two telomere-related genes known as TERT and TERC, are respectively carried by 51 percent and 72 percent of the general population. Because it is somewhat unusual for such risk-conferring variants to be carried by a majority of people, the researchers propose that in these carriers the overall cellular robustness afforded by longer telomeres trumps the increased risk of high-grade gliomas, which are invariably fatal but relatively rare cancers.

The research was published online in Nature Genetics on June 8, 2014.

A recurring theme at FuturePundit: If we could cure cancer we could run the risk of making cells able and eager to divide more times. The problem: On one hand, when aged cells replicate they run the risk of losing control and turning into cancer cells. On the other hand, we need cell replication in order to replace dead and damaged cells.

In undamaged cells long telomeres are good. In damaged cells restraints on cell divisions (and short telomeres are a restraint on cell division) protect against cancer.

“Though longer telomeres might be good for you as a whole person, reducing many health risks and slowing aging, they might also cause some cells to live longer than they’re supposed to, which is one of the hallmarks of cancer,” said lead author Kyle M. Walsh, PhD, assistant professor of neurological surgery and a member of the Program in Cancer Genetics at UCSF’s Helen Diller Family Comprehensive Cancer Center.

A story about how fasting seems to rejuvenate the immune system raises a similar question: Does a rejuvenated immune system as a result of fasting really reduce our risks of dying?

In the first evidence of a natural intervention triggering stem cell-based regeneration of an organ or system, a study in the June 5 issue of the Cell Stem Cell shows that cycles of prolonged fasting not only protect against immune system damage — a major side effect of chemotherapy — but also induce immune system regeneration, shifting stem cells from a dormant state to a state of self-renewal.

In both mice and a Phase 1 human clinical trial, long periods of not eating significantly lowered white blood cell counts. In mice, fasting cycles then “flipped a regenerative switch,” changing the signaling pathways for hematopoietic stem cells, which are responsible for the generation of blood and immune systems, the research showed.

Maybe some of those dormant old immune cells are genetically damaged and at risk of going cancerous. Maybe we are better off if we let cellular sleeping dogs keep sleeping.

What we need: the ability to tell cells with dangerous mutations to kill themselves. Cancers are the result of multiple dangerous mutations all happening in the same cell. If we could, say, send in gene therapy that would detect the risky pre-cancerous mutations and cause those cells to commit suicide (apoptosis for the biologically minded) then we could make our bodies safe enough for therapies that would turn up the knob on the healthy cells that aren't dividing enough.

Share |      Randall Parker, 2014 June 08 08:04 PM 


Comments
Peter Andrews said at June 10, 2014 5:31 AM:

I agree with the general point about not blindly increasing cell life but I think your reference to the second study about immune cell regeneration is slightly off the mark. The immune system rejuvenation occurs post multi-day fasting which does exactly what you were hoping for - accelerates detection and killing of damaged cells. In net, this type of fasting seems to be beneficial.

albatross said at June 10, 2014 10:32 AM:

In the future, I expect that we will be making sure our kids don't have cancer-associated genes (proto-oncogenes, non-functioning tumor suppressor genes). I wonder how the tradeoffs will work out then for things like lengthening telomere caps, by making it harder for the chain of mutations that turns a cell cancerous to happen. Are there any good estimates on what fraction of cancer is likely linked to your original genes?

Nick G said at June 10, 2014 2:52 PM:

What we need: a way to slow down the aging clock.

Nake mole rats live 10x longer than normal rats: both typical senescence *and* cancer are delayed.

I want to know why humans live twice as long (with neither degeneration or cancer) as chimps. Humans evolved relatively recently: what changed?

----------------------

It's reasonable to guess that many interventions will have a tradeoff, but I bet there are interventions that are simply a "panacea" - they just extend lifespan.

Tj Green said at June 11, 2014 5:11 PM:

We have to assume that the naked mole rat has a far superior protein manufacturing system than we have. Most of us die from old age.which is accumulating damage,so our ribosome must be the main contributor to this damage. What we need is a more efficient ribosome and a zero tolerant immune system.

Crocodile Chuck said at June 14, 2014 4:57 PM:

1) @ Nick G @ 2:52 pm: we don't 'need' a way to slow down the ageing clock. As a matter of fact, we have way too many homo sapiens crowding the lithosphere already http://biophilic.blogspot.com.au/2014/06/west-antarctic-ice-sheet-who-cares.html
Remember Steve Jobs' epic 2005 commencement address @ Stanford: 'Death is the greatest invention, ever'. Never forget this concise article of wisdom.

2) @ albatross @ 10:32 am "Are there any good estimates on what fraction of cancer is likely linked to your original genes?" A: a lot. Try this v stimulating paper on the topic by exobiologist Paul Davies:

http://cancer-insights.asu.edu/wp-content/uploads/2012/01/Cancer-tumors-as-Metazoa-1-0-tapping-genes-of-ancient-ancestors1.pdf

More here: http://cancer-insights.asu.edu/2012/02/is-cancer-an-ancient-throwback/

Peace.

Nick G said at June 16, 2014 10:05 AM:

C Chuck,

This may sound aggressive, but it seems like a logical question: why haven't you killed yourself?

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