1. The study used two different DNA genome sequencing chips (analytical electronics), one for the control group and another for the study group. Although the chips were from the same company (Illumina), they are known to have different methodologies. This can lead to bias in the data.
2. The extraordinarily high prediction rate of 77% raises warning flags on general principles.
3. The relatively small number of people tested (sample size of about 1000) in the study.
4. The unusually large size of the SNPs involved. A ‘snip’ (SNP=single-nucleotide polymorphism) is a DNA sequence variation. The longer the SNP, the more likely for variation.
5. Many of the ‘new’ variants found in the study have never been associated with disease (presumably a connection needed for them to increase longevity).
6. None of the SNPs correlated to old age were verified with a different analytical system (from another company).

It is not necessary to grasp all the technical details (and there are many) to get the idea these collectively represent a serious challenge. In scientific parlance…this is a furor. It reaches this intensity when the subject matter is important. Predicting for old age certainly qualifies – knowing whether you have the genes to live to a ripe old age, while not everything, is certainly good (or bad) news. Perhaps more importantly, if these gene variations are really strongly correlated with old age, it means they are also strongly correlated with having good or bad health. That makes these genes potentially a rather large window into the relationships between genes, health, and living a long time. For scientists, it’s like having a new roadmap for ten or twenty years of research.

Naturally the scientists involved with the original study have their own opinions. Although somewhat taken aback by the immediate and often vociferous attack on their research, they were most surprised by the possibility of technical difficulty introduced by using two different generations of the Illumina analytical chip. Here are a few quotes from an interview with the principal authors of the study, Paola Sebastiani and Thomas Perls, both of Boston University:

Q: What do you make of the controversy? Did you expect the paper to be controversial?
P.S.: To be honest, I expected this to be controversial for the type of analysis, and not for some issues with the data. There are very innovative ideas in the paper, … the idea of not really looking at the effect of individual SNPs, but the global effects of several SNPs, … the idea of looking at patterns rather than individual variants. I expected that to generate discussion.
…
P.S.: I think there are errors in every paper. This is part of the scientific debate–from errors, sometimes you can come up with very good ideas.
Q: Do you feel that the results in the paper are generally correct, that they’ll hold up?
P.S.: We want to wait until all the analyses are done.
T.P.: That’s one of the problems that we do not want to contribute to. There have been very premature and harmful proclamations about what the data show or don’t show. I think people need to know that good science takes time, and while people are anxious to know and we completely understand that, we want to be able to do a thorough … analysis.

[Source: Science Insider]

So it’s back to the data for the authors, who promise to have their response(s) in relatively short order. This is called ‘debate’ – with the evidence as the focal point for the discussion. It is not a demonstration of the weakness of scientific research – it is one of the strengths. On the other hand, perhaps the criticism may hold up that this study was pushed forward more by a desire to capitalize on its more sensational aspects than to do a lot of painstaking fact checking. That too is valid scientific criticism as the attitude can sometimes be more powerful than what the evidence will bear.

- The 150 gene ‘markers’ were accurate in predicting longevity 77% of the time. (That’s pretty good, but obviously not perfect.)
- The oldest people, those at 110 or over, were the most likely to have the best prediction rate.
- The researchers developed new statistical techniques (Bayesian, mostly) that could be used to analyze similar gene variant patterns. (This may actually turn out to be one of the more important contributions of the study.)
- The study also analyzed the data for a correlation between the ‘longevity genes’ and the lack of gene variants associated with diseases, but found that people with longevity variants and the control group had about the same number of disease gene variants.
- The study called for specific research into how (and why) these specific SNPs are related to longevity. (That is a fuzzy area for genome-wide research. It provides interesting correlations, but the explanations will have to come much later after laborious research.)
- The presence of these gene variants does not override the importance of environmental and life-style factors in living to an old age. (If you get run over by a truck, they don’t matter. Ditto for smoking, drinking, and eating to excess.)

The authors of the study are (rightly) careful:

If these findings are confirmed, they would suggest that “predicting disease risk using disease-associated variants may be inaccurate and potentially misleading, without more information about other genetic variants that could attenuate such risk” the authors commented.
..
But they added: “This prediction is not perfect, however, and although it may improve with better knowledge of the variations in the human genome, its limitations confirm that environmental factors (e.g., lifestyle) also contribute in important ways to the ability of humans to survive to very old ages.”

Drs. Sebastiani and Perls also cautioned that they developed this genetic risk model as a way to dissect the complex genetic bases of exceptional longevity and to discover the different genetic paths to age 100 and older. An understanding of the implications of this model’s use in the general population would be necessary before this test is marketed, they said.

[Source: EurekAlert]

Will we someday (soon) ask, “You got gerontogenes?”

Telomeres are ‘tag ends’ of our DNA chromosomes. In the process of reproducing cells, the telomere signals where to stop transcribing genes. However, during the process of mitosis, when the DNA duplicates and a new cell is created, sometimes the telomere is cut (snipped) before the end. It becomes shorter. Eventually there may be no telomere remaining, and the cell will fail to replicate. This has been shown to relate to the aging process (SciTechStory, November 9, 2009: Study confirms telomere’s role in living longer).

Normally DNA attempts to keep the chromosomal telomeres at the proper length. In fact, it has at least one gene associated with the task: telomerase RNA component or TERC. The research shows that some people have variations, either in TERC or genes associated with it that prevent TERC from working properly. These people age early, or fall prey to diseases of old age earlier.

Professor Tim Spector from King’s College London and director of the TwinsUK study, who co-led this project, added:

“The variants identified lies near a gene called TERC which is already known to play an important role in maintaining telomere length. What our study suggests is that some people are genetically programmed to age at a faster rate. The effect was quite considerable in those with the variant, equivalent to between 3-4 years of ‘biological aging” as measured by telomere length loss. Alternatively genetically susceptible people may age even faster when exposed to proven ‘bad’ environments for telomeres like smoking, obesity or lack of exercise – and end up several years biologically older or succumbing to more age-related diseases. ”

[Source: EurekAlert]

Identification of the variant genes is, of course, just a start. Analyzing the relationship between ‘normal’ and ‘variant’ genes and how they affect the reproduction of telomeres is a next step. As with much of the work on gerontology – this avenue of approach is many years away from producing something to counteract the effects of aging.

Almost a third of the “impact areas” listed here at SciTechStory contribute to the coming reality of an Extended Lifespan (also an impact area): DNA Decoding, Cell Biology, Brain Enhancement, Medical Robotics, Major Disease Cures, Nano-medicine, Bio-implantation, Neuro-intelligence, Scientific Instruments, Sensor Technology, Stem Cells, and Synthetic Organs. Collectively these impact areas represent the research work – and important advances – in a fleet of disciplines: Neuroscience, genetics, molecular biology, nanotechnology, robotics, gerontology, pharmacology…to name but a few. It’s not like expanding the span of human life is the be-all-end-all for most of this research, but for most it’s a direct result. If major diseases can be cured, people will live longer. If cell biology discovers how to reverse the deterioration of aging, people will live longer. If body parts can be repaired or replaced through bio-implantation, synthetic organs, or stem cells, people will live longer. And so forth…

A recent article in the English publication, The Guardian, highlighted the issue: Great expectations: today’s babies are likely to live to 100, doctors predict.

Most babies born in the past few years in the UK will live to be 100 if current trends continue, experts say.

And people could be living not only longer, but better, according to doctors writing in the Lancet medical journal, who say that most evidence shows the under-85s are tending to remain more capable and mobile than before. They have more chronic illnesses, such as cancers and heart conditions, but people survive them because they are diagnosed earlier and get better treatment.

Professor Kaare Christensen and colleagues at the ageing research centre at the University of Southern Denmark calculate that at least half the babies born in the UK in the year 2000 will reach their 100th birthday. Life expectancy is increasing so fast that half the babies born in 2007 will live to be at least 103, while half the Japanese babies born in the same year will reach the age of 107.

The ‘we’re going to live longer’ scientific literature is becoming common. Perhaps you have heard or read about it yourself. Do you believe it? [Personal anecdote: My father was lamenting to my aunt about the poor state of the world. This was in 2001. My aunt replied, “Yes, but we’re living longer.” She died at 93, despite life-long epilepsy and eventually Alzheimer’s. My father lived to 99.] The confirming statistics are everywhere: The number of centenarians is increasing by about 7% a year. The average life-span in Medieval Britain was 20-30 years. By the early 20th Century it was 30-40 years. Now it is approximately 75 years.

The question about when this will happen – when will most people live to 100? – is answered by “starting now, in developed countries.” Starting probably within a few decades for much of the rest of the world. Keep in mind that the world average is already at 65 years of life.

All this means that we’d better not forget demographics when it comes to looking at the future. For example, how should we plan for social security (of whatever kind), when people routinely start living 90-100 years? What happens to the nature of work, and employment, when the difference between the end of work (now around 65) and death is no longer ten or twenty years, but thirty and forty years? How do our health care systems adjust to a radically aging population?

These questions barely scratch the surface.

Meanwhile the research goes on, not just apace but at an advancing pace. People living now will benefit from the discoveries yet to come, but it’s our children who will see the most change and have to deal with the most consequences.

Berkeley — A study led by researchers at the University of California, Berkeley, has identified critical biochemical pathways linked to the aging of human muscle. By manipulating these pathways, the researchers were able to turn back the clock on old human muscle, restoring its ability to repair and rebuild itself. The findings will be reported in the Sept. 30 issue of the journal EMBO Molecular Medicine, a peer-reviewed, scientific publication of the European Molecular Biology Organization.

The key point from this post in FuturePundit is that, yes we can probably induce more repair to muscle cells in older people, but there is almost always a trade off. Maybe we should call it the ‘trade-off principle’ of research, and apply it systematically.

If the body is turning down MAPK and suppressing stem cells as we age there’s probably a constructive reason for this. The most obvious possibility: the repair stem cells are turned down because as they age they become higher risks for turning cancerous. If that is the case (and I think it likely) then efforts to turn up stem cells to do more repair will put us at greater risk of cancer. Therefore we really need effective ways to kill pre-cancerous and cancerous cells as essential capabilities in order to do rejuvenation therapies.