Statistical kinetic approach for modeling lifespan.
Lifespan regulation through gene expression involves complex biochemical processes. Unfortunately, current mathematical models for treating lifespan data afford little insight into the mechanisms that control longevity. In this work, we demonstrate the use of a novel kinetic model to successfully fit the lifespan curves of the nematode, Caenorhabditis elegans. Our findings show that population aging may be treated analogously to a dispersive chemical process [P.J. Skrdla, R.T. Robertson., J. Phys. Chem. B 109 10611 (2005)]. Much like the Gompertz model, only two fit parameters, alpha and beta, are needed to adequately describe the entire data set for each nematode population. These parameters relate a 'global first-order time constant' and a 'global second-order rate constant', with units of (time) and (time)(-2), respectively. In C. elegans, the increased longevity resulting from DAF-16 (a transcription factor) activity in the intestinal tissue correlates with a larger alpha value and a smaller beta value; the opposite is true for animals with shorter lifespans. A basic physical interpretation of the two parameters is provided.
Skrdla
Peter J
PJ
D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D015233:Models, Statistical; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans