2 replies to this topic

[treonsverdery]

Ubiquination http://en.wikipedia.org/wiki/Ubiquitin is a cytoprocess that recycles proteins. The biochem tome Im looking at says The structural features that direct recyling are the N terminal amino acid on the protein, if it is asp, leu, lys, phe then the protein has a half life of just 2 or 3 minutes if it has ala, gly, met, ser, val then it has a half life over ten hours. so basically if you want any protein to be rapidly recycled you just end it with a 2or3 minute amino acid, if you want 200 times greater protein durability just end it with a ten hour amino acid

So when you look at a genetic change to any existing human protein coding gene to create superlongevity you could look at changing just that one amino acid on the gene at the N terminal to create a version 200 times more durable. Now of course this has a variety of interpretations, with CR protein recycling is actually more rapid, some have hypothesized that this keeps things looking new, thus functioning better. Thus changing the N terminal amino acid at some of the genes that code things like collagen, elastin, G coupled protein receptors, would create variously hyperdurable or quickly rebuilt versions, then we would see which mice have ever youthful skin as well as rapidly renewing keen senses.

Edited by treonsverdery, 08 February 2012 - 06:12 PM.

[treonsverdery]

changing one codon at TERT the telomerase gene to give 200 times longer duration at the cytosol giving greater longevity

[steampoweredgod]

Well the issue is that it is very likely the recycling rate per protein is set by evolution depending on multiple factors:

1. how resistant the protein is to damage(this depends on composition of aminos of the rest of the protein, where its at, what reactions might affect it, etc some proteins are more impervious to damage and can thus be recycled at a slower rate others need be recycled faster)
2. Regulation of protein function, it may need to be eliminated or diminished at certain times augmented at others depending on circumstances(the rate of recycling is likely optimized to work in conjunction with likely production changes for the protein involved and the time and concentration required for optimal function )
3. Costs of keeping damaged proteins around(if the protein is damage prone there may be varying levels of tolerance for having such damaged proteins around.)

From what I understand there are also changes such as AGEs, that cannot normally be reversed, in cases were multiple chemical steps are necessary, recycling faster will slow the accumulation of such damage. That said I've heard that birds manage to keep high levels of blood glucose as well as high temperature, both of which should increase the likelyhood of AGE formation, yet I've also heard that in some species tissue examination appears to show agelessness in certain tissues. It may be that either mechanisms to slow AGE formation are present or that there are mechanisms to deal with such in some species.


With regards to telomerase, you can achieve similar by increasing expression of it.*(either via genetic modification, or by pharmacological factors that may influence its regulation in a positive manner.) The long term problem is the possibility of a cancer that may run out of control.

Edited by steampoweredgod, 18 February 2012 - 11:44 PM.