Nevner at respirasjonsrate styrer mer en 73% av livlengden. Respirasjonsrate er ikke det samme som pustefrekvens, men lavere pustefrekvens vil også påvirke respirasjonsraten i mitokondriene.

Den nevner to tilsynelatende motstridene teorier: den ene sier ROS aktivitet øker aldringshastighet, den andre sier at ROS akivitet setter igang forsvarsmekanismer som senker aldringshastighet.

Vi lever lengst om vi har høy respirasjonsrate og sterkt forsvar mot ROS.

I restitusjonspust, med høy CO2 som gir lav affinitet for O2 i blodcellene, vil mer O2 hoppe over til mitokondriene. Så selv om vi har lavere metabolisme får vi sannsynligvis både større utnyttelse av oksygen (høyere respirasjonsrate) og et sterkere forsvar mot ROS.

http://www.fasebj.org/content/21/4/1271.long

Moreover, we show that frh-1-inhibiting RNAi impairs oxygen consumption and that respiratory rate is positively correlated with life span in this multicellular eukaryote (r=0.8566), suggesting that >73% of life span variance in C. elegans is explained by changes in respiratory rate.

Not surprisingly, the underlying hypotheses are conflicting: one line of evidence suggests that down-regulation of mitochondrial metabolism causes decreased formation of reactive oxygen species (ROS), a mandatory by-product of mitochondrial electron transfer (20⇓ , 21)⇓ . This hypothesis is essentially a modernized version of the rate-of-living theory (22)⇓ , which in later years was focused on detrimental effects of ROS by Harman (23)⇓. The other and conflicting line of evidence suggests that induction of mitochondrial metabolism might induce a positive response to increased formation of ROS and other stressors, leading to a secondary increase in stress defense following primary induction of stress, cumulating in reduced net stress levels (24⇓ 25⇓ 26⇓ 27)⇓ . The process has been named hormesis (28)⇓ . Whether it applies to processes extending life span is currently a matter of fierce debate (26)⇓ .

Moreover, a potential role of increased respiration to extend life span in eukaryotes has been suggested for the unicellular eukaryote S. cerevisae in states of caloric restriction (29)⇓ , a known regimen to extend life span in eukaryotes including mammals (30⇓ , 31)⇓ . Recent evidence has questioned the role of increased respiration in regards to S. cerevisae (32)⇓ . It should be noted though that these observations are conflicting, but mechanistically not at all mutually exclusive, since both pathways (sirtuin-activation vs.mTOR) may coexist independently of each other.

We here have shown that life span in the multicellular eukaryote C. elegans is positively correlated to respiratory activity. Since increased respiration may cause increased formation of ROS, we tentatively assume that decreased life span due to reduced levels of respiration reflects a reduction of hormetic responses to systemic stressors. This assumption is supported by findings in fibroblasts where frataxin was overexpressed: these cells show increased respiration and increased oxidative phosphorylation (3)⇓ , while formation and accumulation of ROS in these cells are decreased due to induction of antioxidant defense capacity (33)⇓ .