[extropy-chat] ROS and aging

[Joao Magalhaes]

Hi,

Here are a couple of recent papers on ROS and aging that called my 
attention--hope this is not a repost.

First of all, overexpression of glutamate-cysteine ligase extends lifespan 
in Drosophila by up to 50%:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16148000&query_hl=210

Glutamate-cysteine ligase is involved in glutathione synthesis, that can 
act as an antioxidant. The highest life-extension was due to overexpression 
in the brain, which is similar to previous results with SOD. So far, 
manipulations of the glutathione system in mice have failed to affect 
aging, but this particular genes has not been tested. In mammals, I believe 
the glutathione system mostly acts on oxidative defence in 
erythrocytes--though it has other functions. Mutations in these genes in 
humans have been associated with anemia but polymorphisms have been linked 
with myocardial infarction. This system could thus be similar to what we 
saw with catalase: overexpression leads to life-extension in Drosophila 
and, in mice, has a protective effect of cardiac disease but does not 
impact on the whole aging process. We'll see if they develop some similar 
model in mice.

In the next paper they created a Drosophila strain with high levels of 
antioxidants and a lower production of ROS. Interestingly, the animals 
actually live less than controls:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15954861&query_hl=112

This seems to support the idea that ROS are not just damaging compounds, 
but essential biological molecules used in a myriad of functions. On this 
subject, I have a paper on ROS that could be of interest to some of you:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16226003&query_hl=116

Lastly, here's another recent paper showing that antioxidant protection 
does not correlate with longevity in rodents, in line with many other 
results suggesting that antioxidant protection is already optimized in mammals:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16087218&query_hl=112 


Cheers,

Joao


---

Joao Pedro de Magalhaes, PhD

Harvard Medical School, Dept. of Genetics
77 Avenue Louis Pasteur, Room 238
Boston, MA 02115
Telephone: 1-617-432-6512

http://www.senescence.info