Mortality, fidgeting and sitting

"As other studies have, the team found that longer time spent sitting was linked to mortality. Among women sat for more than seven hours per day and who didn’t fidget much, their risk of mortality was 43% higher than those who sat for less than five hours. (When the team adjusted for things like smoking and drinking, the mortality risk for sitting for more than seven hours a day was still higher by 30%.)

But what was really interesting was that being more fidgety seemed to counteract this effect: That is, the middle- and high-fidgeting groups didn’t have any greater risk of death even sitting more than seven hours every day."-forbes link

It seems that there is a way that might counteract the detrimental effects of prolonged sitting.  Simply moving a bit constantly appears to offset the increased mortality

Marathon improves mortality but it seems excess can wipe the benefits or does it?

 But while a study of 52,600 runners showed that pounding the pavement can yield a 19 percent lower mortality rate, that benefit was wiped out for those tallying 20 to 25 miles a week. Not exactly sure how those stats work because we all die eventually.-link

I'm planning to do about 12-15 miles per week as part of my training regimen

 ...As cardiologist Paul Thompson says in the WSJ piece, "The guys advancing the hypothesis that you can get too much exercise are manipulating the data... They have an agenda."
 ...
 Wen and colleagues reply that yes, they do have data -- and it doesn't show what O'Keefe et al. hope:
...
We were not able to identify an upper limit of physical activity, either moderate or vigorous, above which more harm than good will occur in terms of long-term life expectancy benefits...-link

It seems there are counterpoints to the arguments for moderation but still extremes should likely be cautiously avoided

Moderation seems to provide benefits with about 7mph being optimal at 10-15 miles per week with less than 7 days of running that is with resting days.

 
Regarding pace, individuals who ran six and seven miles per hour had a significant 21% and 27% lower risk of all-cause mortality, whereas those who ran eight or more miles per hour had a nonsignificant 7% lower risk of all-cause mortality.-link

There may be hope for damaged hearts

 In an act of transformation worthy of any magician, scientists have converted scar tissue in the hearts of living mice into beating heart cells. If the same trick works in humans (and we’re still several years away from a trial), it could lead us to a long-sought prize of medicine – a way to mend a broken heart.-link

In contrast to other oxidative modifications of amino acids, methionine sulfoxide can be enzymatically reduced back to methionine in proteins by the peptide methionine sulfoxide reductase system, composed of MsrA and MsrB. The expression of MsrA and one member of the MsrB family, hCBS-1, was analyzed during replicative senescence of WI-38 human fibroblasts. Gene expression decreased for both enzymes in senescent cells compared to young cells, and this decline was associated with an alteration in catalytic activity and the accumulation of oxidized proteins during senescence. These results suggest that downregulation of MsrA and hCBS-1 can alter the ability of senescent cells to cope with oxidative stress, hence contributing to the age-related accumulation of oxidative damage.-link

Methionine intake has been linked to lifespan, methionine is said to be easily damageable.  Methionine sulfoxide reductases help deal with this damage, yet it seems that senescence results in downregulation of these protective enzymes.   Some say the regular aging process also results in reduction of production of these enzymes, along with the said increase in membrane peroxidation index, the cells would become more damage prone with increasing age.   It is said every ten years, after approx maturity, there's a doubling of mortality.   Why are changes that increase cellular damage taking place?  It's clear that such changes might exceed the maintenance mechanisms of the cells and be behind this increased probability of death.