Protein
turnover maintains the proteome’s functional integrity.
Here, protein turnover efficiency over time in wild-type Caenorhabditis elegans was assessed using inverse
[15N]-pulse labeling up to 7 days after the egg-laying
phase at 20 °C. Isotopic analysis of some abundant proteins was
executed favoring data quality over quantity for mathematical modeling.
Surprisingly, isotopic enrichment over time reached an upper limit
showing an apparent cessation of protein renewal well before death,
with protein fractions inaccessible to turnover ranging from 14 to
83%. For life span modulation, worms were raised at different temperatures
after egg laying. Mathematical modeling of isotopic enrichment points
either to a slowdown of protein turnover or to an increasing protein
fraction resistant to turnover with time. Most notably, the estimated
time points of protein turnover cessation from our mathematical model
were highly correlated with the observed median life span. Thrashing
and pumping rates over time were linearly correlated with isotopic
enrichment, therefore linking protein/tracer intake to protein turnover
rate and protein life span. If confirmed, life span extension is possible
by optimizing protein turnover rate through modulating protein intake
in C. elegans and possibly other organisms.
While proteome maintenance benefits from a high protein turnover rate,
protein turnover is fundamentally energy-intensive, where oxidative
stress contributes to damage that it is supposed to repair.
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