Module 4 · Free Radical and Mitochondrial Theories

Pérez and colleagues, 2009, citing that paper: oxygen free radicals formed in normal metabolism play a role in aging because oxidative damage to macromolecules increases. The 1956 paper has no abstract in Europe PMC (Figure 1).

Life span and average mass-specific metabolic rate are inversely proportional, as Vaanholt and colleagues, 2009, state it. They say it was rejected because birds have higher metabolic rates than mammals of the same size and yet live longer. The 1928 book has no Crossref DOI (Figure 1).

Sastre, Pallardó, and Viña, 2000, say Harman suggested that mitochondria might be the biological clock, with oxygen consumption setting the rate of free-radical damage to mitochondria. The 1972 paper has no abstract here. The title is a question (Figure 1).

They point to an inverse correlation between species longevity and the mitochondrial generation of superoxide and hydrogen peroxide, not to oxygen consumption itself. The Drosophila support in that abstract has no percentage (Figure 1).

Mitochondria-targeted catalase: average increases of 5 months in median lifespan and 5.5 months in maximum lifespan, with less damage. The abstract does not give the starting median, so 5 months is not converted to a percent (Figure 3).

Trifunovic: a three- to fivefold rise in point mutations, more deletions, a shorter life, and a premature-aging phenotype. Kujoth: accelerated-aging features without increased markers of oxidative stress. Do not give Kujoth's oxidative result to Trifunovic (Figure 3).

It is mitochondrial DNA versus nuclear DNA, in 10 people aged 42 to 97. The 15-fold is the same comparison in those older than 70. The abstract says the damage rose with age and does not give a fold for that rise (Figure 2).

Fifty percent manganese superoxide dismutase, more oxidative DNA damage, 100 percent more old mice with a tumor, and identical mean and maximum lifespan (Figure 3).

JAMA 2007: all trials together, relative risk 1.02, not significant; low-bias trials, 1.05, a small increase. The Cochrane review of that question is 2008, updated in 2012. It is not a 2007 Cochrane review. The 2012 authors found no evidence to support the supplements (Figure 3).

In healthy young men, four weeks of exercise raised insulin sensitivity only without vitamins C and E. It did not measure lifespan. Mitohormesis, as Ristow and Zarse name it, treats the reactive oxygen species as a signal (Figure 4).

They do not show that copying errors in blood, deleted mitochondrial DNA in a muscle disease, or an NAD precursor produced the historical rise in population life expectancy. The blood finding does not rule oxidative damage out of aging generally (Figure 5).