For example, calorie restriction, a well-studied manipulation that extends the life span in diverse organisms, was found to reduce macromolecular damage to proteins in rodents. (3,4) Support for the role of macromolecular damage in age-dependent decline arises from studies that explore the effects of life span-enhancing manipulations on macromolecular damage. (2) Accumulation of protein damage over time may result in organelles, cells, and eventually organ systems to lose their ability to execute functions required for the continued survival of the organism. Extrinsic factors include UV-light exposure, natural radiation, and food-induced biochemical reactions as well as posttranslational modifications. Intrinsic stress factors include modifications by chemical reactions including changes induced by reactive oxygen species from metabolic processes. (1) This is particularly true for proteins as the machinery of life. Many biological macromolecules are thermodynamically inherently unstable and therefore are constantly at risk of being damaged by intrinsic metabolic processes or extrinsic factors. 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. If confirmed, life span extension is possible by optimizing protein turnover rate through modulating protein intake in C. 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. Most notably, the estimated time points of protein turnover cessation from our mathematical model were highly correlated with the observed median life span. Mathematical modeling of isotopic enrichment points either to a slowdown of protein turnover or to an increasing protein fraction resistant to turnover with time. For life span modulation, worms were raised at different temperatures after egg laying. 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%. Isotopic analysis of some abundant proteins was executed favoring data quality over quantity for mathematical modeling. ![]() Here, protein turnover efficiency over time in wild-type Caenorhabditis elegans was assessed using inverse -pulse labeling up to 7 days after the egg-laying phase at 20 ☌. Protein turnover maintains the proteome’s functional integrity.
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