Linking RAGE Variations to Longevity
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Advanced glycation end-products (AGEs) build up with age in our tissues, gumming together protein machinery and causing chronic inflammation and other bad behavior on the part of cells through the receptor for AGEs, or RAGE. Thus we should probably not be completely surprised to see associations between variations in RAGE and natural variations in longevity. This reinforces the need for AGE-breakers: treatments that can effectively break down and wash out AGEs, removing the harm that they do. Unfortunately few groups are working on this, despite the fact that there is apparently only one important type of AGE in human tissue.

Demographic and social changes in the last decades have resulted in improvements in health and longevity. The survival of elderly people has improved significantly and thus centenarians are becoming the fastest growing population group. Environmental, genetic, and accidental factors have influenced the human life span. Researchers have gained substantial evidence that advanced glycation end products may play an important role in the processes of physiological aging. The aim of the present study was to investigate any differences in the frequencies of -374T/A polymorphism [of the RAGE gene] in subjects aged 90 years or older and in middle-aged individuals.

We observed association between the A allele and genotype homozygous for this allele (AA) with a longer life expectancy in the male population. In particular, there was a prevalence of AA genotype and A allele in long-living subjects and a prevalence of the allele T in middle-aged subjects, indicating a possible protective role of the allele A to aging. In conclusion, our results support the hypothesis that longevity is the result of a good functioning of the immune system and a presumable hyper-expression of variants of anti-inflammatory genes of immunity. The differences in the genetic regulation of inflammatory processes may influence the presence of age-related disorders.

Link: http://dx.doi.org/10.3390/ijms141123203

Comments

I still don't understand why there isn't any pharma investment in this area?

If glucospane leads to a lose of elasticity in the skin, and inflammation in the skin, then surely an glucospane removal drug or enzyme would have a postive cosmetic effect on the skin of anyone over the age of 21.

So given this potentially huge financial sales reward, why is no major company investing in this??

Posted by: Jim at December 3, 2013 4:56 AM

The most likely reasons are because there's no theraputic target for it, and that there's too much risk that it won't pan out in some critical way.

"No theraputic target" is a very specific phrase, if you haven't heard it before: it means that there's no "treatable condition" associated with something. Yeah, that thing might obviously be bad, and yeah, you could make a pretty significant argument that getting rid of it would vastly improve things - but without a theraputic target, you can't point to a specific thing that it treats which is on the "list of approved maladies you're allowed to treat". It's a bureaucratic obstacle from a few decades ago, which is only beginning to be pried open in the face of new evidence, for example with 'frailty' only recently being considered a 'treatable condition'.

The "risk" reason merely compounds this. There's the chance that it will have very little effect, that finding cleaving agents is incredibly hard, that non-toxic cleaving agents can't be found, that breaking it actually causes more damage than it fixes, that the majority of linkages are protected in a way that makes them inaccessible, etc.

Those two together mean that it's effectively up to 'blue sky' research like SENS and universities, at least for the moment.

On a related topic, this is why the SENS K7C and A2E projects are so incredibly important: if these can be brought to human trials/proof of concept, it opens up an entire field of remedies which were previously off the table. It's not that SENS will do the work and save us all - it's that SENS is going ahead of everyone else, drawing maps, marking paths, and opening doors to make it easier for the heavy hitters to get involved.

Posted by: Dennis Towne at December 3, 2013 1:26 PM

Thanks Dennis, that is a really good, concise answer.

Posted by: Jim at December 3, 2013 6:16 PM
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