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Can Aging Be Cured?

npr.org

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Re: Can Aging Be Cured?

#2
IIRC from my molecular biology class, the biggest (or maybe one of the biggest?) problems is about Telomeres[1].

I was impressed by this study[2]: "Lifestyle Changes May Lengthen Telomeres, A Measure of Cell Aging".

[1] http://en.wikipedia.org/wiki/Telomere

[2] http://www.ucsf.edu/news/2013/09/108886/lifestyle-changes-ma...

Re: Can Aging Be Cured?

#3
Here is the transcript for those who missed that easily-overlooked link:

http://www.npr.org/templates/transcript/transcript.php?story...

"Things that have only a 50 percent chance of happening in 20 years from now are supposed to sound like science fiction."

This interview with de Grey is one part of a longer piece with other interviews:

http://www.npr.org/programs/ted-radio-hour/408023272/the-fou...

Of which the one with Cynthia Kenyon is also interesting, particularly as a contrast on fundamental philosophy and strategy in the approach to treating aging as a medical condition:

http://www.npr.org/templates/transcript/transcript.php?story...

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Aubrey de Grey is the cofounder of the SENS Research Foundation and coordinator of rejuvenation research programs. Cynthia Kenyon worked on single gene manipulations that extend nematode longevity back in the 1990s, efforts that arguably kicked off the modern wave of interest in slowing aging.

In these two short interviews you can see illustrated the most important division in the modern work aimed at intervention into the aging process: on the one hand the mainstream approach of altering the operation of metabolism so as to slow down aging, based on traditional drug discovery methodologies, and on the other hand the radical, disruptive approach of repairing the damage caused by the normal operation of metabolism, requiring the development of new biotechnologies. The strategy here is to avoid changing the operation of metabolism, because that is very hard and far too little is known of the important details, but rather periodically clean up the consequences of normal metabolic activity in order to prevent that damage from overwhelming and altering biological systems so as to cause degenerative aging.

I'm greatly in favor of the latter approach because all the signs suggest it should be far more efficient and effective at extending healthy life spans, not to mention producing actual rejuvenation in the old. You can't greatly help the old by slowing down aging: better technologies are needed. Rejuvenation is needed. You can't bring aging under medical control by working on metabolic alteration to slow aging. Repair is needed, not merely dialing down the pace of new damage.

Re: Can Aging Be Cured?

#4
post #2

IIRC from my molecular biology class, the biggest (or maybe one of the biggest?) problems is about Telomeres[1]. I was impressed by this study[2]: "Lifestyle Changes May Lengthen Telomeres, A Measure of Cell Aging". [1] http://en.wikipedia.org/wiki/Telomere [2] http://www.ucsf.edu/news/2013/09/108886/lifestyle-changes-ma...

Telomeres are repeating sequences of nucleic acids that cap the ends of chromosomes in the cell nucleus and stop actual gene-coding DNA from being chopped off when a cell divides. The mechanisms of DNA replication require extra leg room at the ends of the strand, a trailing sequence that is not copied over to the new strand under assembly - and the primary role of telomeres is to be the part that is dropped on the floor. A little of their length is thus lost with every cell division. This shortening acts as a clock to count cell divisions, and cells with very short telomeres stop replicating - they either enter cellular senescence (which ideally then causes the immune system to destroy them) or destroy themselves directly via programmed cell death mechanisms.

Telomere length is more dynamic than this simple picture, however. In some cell populations, such as the various types of stem cell that maintain tissues and produce new cells to replace those lost or damaged, an enzyme called telomerase continually lengthens telomeres so as to allow a cell lineage to continue dividing indefinitely.

Ordinary, non-stem cell populations exhibit a range of telomere lengths, some short, some long. You might imagine that a population of cells replenished more frequently or recently by stem cells will have longer telomeres on average. A population that is receiving less support might have shorter telomeres. Researchers have shown that a higher proportion of short telomeres in white blood cells correlates well with ill health or stress, and somewhat correlates with age. Some more complex measures of telomere length, a step above just taking the average, have been shown to correlate well with age, however, and other techniques do a fair job of predicting future life expectancy in laboratory animals.

A few years back a brace of startup biotech companies were aiming to address aspects of aging by lengthening telomeres through the use of telomerase. None of that went anywhere, unfortunately, but it's possible that they were just too early - it is frequently the case that all of the first batch of companies in a new area of biotechnology fail. It's a tough business to be in. I was a skeptic at the time regarding their potential for success based on my expectation that telomere length will prove not to be a root cause of aging. It looks a lot more like a marker for (a consequence of) some of the responses to the root causes of aging, in particular the reduction in stem cell activity that is characteristic of old age.

Nonetheless, researchers are demonstrating extension of life in mice through telomerase these days, but it is as yet unknown as to exactly why this works. Perhaps it makes stem cells work harder to maintain tissues, perhaps there is just one critically limiting type of stem cell or tissue that benefits from more telomerase, or perhaps it involves other effects causes by increased levels of telomerase that have nothing to do with telomere length. It is worth bearing in mind that there are considerable differences in natural levels of telomerase and the resulting telomere dynamics between mice and people, however. Telomerase therapy is probably not something you'd want to just up and try without the research community first obtaining a much greater understanding of why it works to extend life in mice.

Why? Well, the risk of telomere lengthening in humans is cancer. Any mechanism that globally, or possibly even narrowly, extends telomere length in people will raise the risk of suffering cancer. The whole system of telomere dynamics and cellular senescence is intimately tied to the processes of cancer suppression, while all cancers evolve ways of lengthening their telomeres to allow unlimited cell division. Boosting your telomerase levels looks a lot more risky to me than, say, undergoing first generation stem cell transplants.

There continues to be a lot of activity in telomere research and development. The present brace of telomere-related biotech startups are commercializing ways to measure telomere length rather than extend it. The products are tests that will at first add another measure to inform patients on the state of their health, then possibly act as an effective biomarker of biological age, and perhaps later prove useful in further research if it turns out that telomerase-based therapies can be beneficial in humans.

Re: Can Aging Be Cured?

#5
post #2

IIRC from my molecular biology class, the biggest (or maybe one of the biggest?) problems is about Telomeres[1]. I was impressed by this study[2]: "Lifestyle Changes May Lengthen Telomeres, A Measure of Cell Aging". [1] http://en.wikipedia.org/wiki/Telomere [2] http://www.ucsf.edu/news/2013/09/108886/lifestyle-changes-ma...

Unfortunately, this "problem" was already solved a long time ago... by cancer cells ! [1]

It turns out that having immortal cells (by either avoiding death signals or by having "enhanced" replicative machinery is a great way to develop cancerous cells. So you have to carefully regulate the lifetime of the cell... which is what telomere are doing in the first place.

[1] Many many sources, but for instance the "Enabling Replicative Immortality" of Hanahan&Weinberg 2011, "The Hallmarks of Cancer: the next generation" http://www.sciencedirect.com/science/article/pii/S0092867411...

Re: Can Aging Be Cured?

#7
post #2

IIRC from my molecular biology class, the biggest (or maybe one of the biggest?) problems is about Telomeres[1]. I was impressed by this study[2]: "Lifestyle Changes May Lengthen Telomeres, A Measure of Cell Aging". [1] http://en.wikipedia.org/wiki/Telomere [2] http://www.ucsf.edu/news/2013/09/108886/lifestyle-changes-ma...

Unfortunately, this "problem" was already solved a long time ago... by cancer cells ! [1] It turns out that having immortal cells (by either avoiding death signals or by having "enhanced" replicative machinery is a great way to develop cancerous cells. So you have to carefully regulate the lifetime of the cell... which is what telomere are doing in the first place. [1] Many many sources, but for instance the "Enablin…

Right. Furthermore, our cells have many of other mechanism besides telomeres whose function is to prohibit immortality in a way that's difficult to bypass. (If it were easy to bypass, then it would be less effective at suppressing cancer.)
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