cron-web.org

[A1CR]

Here's some more interesting evidence from CRON4healthyfuture (February 6, 2004 ) that free radicals may not be the "enemy," but in fact an important signaling mechanism to "tune your cells into higher tolerance for oxidative stress." The old adage -- "whatever doesn't kill you makes you stronger" (aka hormesis) may have some truth to it:

1) In the past, scientists had trouble reconciling their cherished
notion of a linear relationship between oxidative stress and aging
with the conventional wisdom that exercise, an enterprise flush with
radicals, is healthy. Organisms with constitutive defects in
oxidative stress management had shortened lifespan, so how could it
be that exercise helps you?

It is now becoming increasingly obvious that the relationship between
oxidative stress and aging is not linear, and that exercise may
actually "tune" your cells to higher tolerance for oxidative stress
through short-term exposure to "adverse" conditions. In fact, there
is some evidence that exercise will actually increase lifespan
14615275, and the generally adaptive and beneficial influence of
exercise on cellular "stress resistance" is being confirmed in
progressively more rigorous experimental condition. 14738474 14754995


Exercise physiologists are even beginning to advance the notion that
reactive oxygen species, or ROS, must be regarded as not a toxic
waste product but as a "signal". 14748544

2) Now this one is particularly fascinating. I wrote a dopey
description a good many months ago back in June of what scientists
call "plasmalogens", and there were some very preliminary suggestions
that these substances associate with DHA to "trap" radicals. DHA,
abundant in fish oil, is highly peroxidizeable, but when incorporated
into membranes, it only seems to help. Scientists had been toying
with the notion that DHA is a "fall guy" that lets itself be
oxidized, and that it "preferentially" tosses the "hot potato"
radical electron to "plasmalogens", these funky fatty acids that sit
around the membrane. These special "plasmalogens" soak up the
radicals from DHA and prevent a "chain reaction" from degrading the
entire membrane, for if that "hot potato" escaped, it will spread
like wildfire through polyunsaturated (vegetable) fats in the
membrane. So, the DHA-plasmalogen system is essentially a free
radical "sink". It's so weird I have trouble believing it entirely,
but it shows how things are complicated in biomembranes. This system
can apparently prevent the oxidation of cholesterol. 14748736
14748734

3) While double-strand breaks to DNA have recently emerged as a
potentially unifying concept in terms of understanding mammalian
aging, there is the issue of lipofuscin and "proteinaceous garbage"
accumulation that occurs in cells, especially as they senesce/age.
The preservation of the activity of lysosomes and "proteasomes" may
be necessary to prevent the accumulation of garbage like lipofuscin
throughout the cell. It has been found that in neurons, loss of the
ability to degrade garbage hurts the neurons and accelerates the
age-related increase in lipofusin 14742431. In contrast, if you beef
up the proteasome in cells, they get tough 12736271. IGF-1, a growth
factor currently implicated in CR, decreases the activity of the
proteasome and general housecleaning 14726748. Insulin itself also
decreases the activity of the proteasome 12773120. A very
fascinating demonstration of how slowly this "proteolytic" pathway
responds to "refeeding" is seen in 12563002, where despite higher
insulin and lower cortisol, rats that had been "starving" are still
on "catabolic" mode, further demonstrating the nonlinearity of
biological systems that may make the Mattson research very
interesting. CR cranks up the activity of the proteasome again, even
in old rodents 11976185.