title: Stability analysis of a model gene network links aging, stress resistance, and negligible senescence.
abstract: Several animal species are considered to exhibit what is called negligible senescence, i.e. they do not show signs of functional decline or any increase of mortality with age. Recent studies in naked mole rat and long-lived sea urchins showed that these species do not alter their gene-expression profiles with age as much as other organisms do. This is consistent with exceptional endurance of naked mole rat tissues to various genotoxic stresses. We conjectured, therefore, that the lifelong transcriptional stability of an organism may be a key determinant of longevity. We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable. Over a time it undergoes an exponential accumulation of gene-regulation deviations leading to death. However, should the repair systems be sufficiently effective, the gene network can stabilize so that gene damage remains constrained along with mortality of the organism. We investigate the relationship between stress-resistance and aging and suggest that the unstable regime may provide a mathematical basis for the Gompertz "law" of aging in many species. At the same time, this model accounts for the apparently age-independent mortality observed in some exceptionally long-lived animals.
authors: Moscow Institute of Physics and Technology, 141700, Institutskii per. 9, Dolgoprudny, Moscow Region, Russian Federation.|Gero Limited, Unit 1, 12/F, International Commerce Center, 1 Austin Road West, Kowloon, Hong Kong.
authors: Valeria
authors: V
authors: Kogan
authors: Moscow Institute of Physics and Technology, 141700, Institutskii per. 9, Dolgoprudny, Moscow Region, Russian Federation.|Gero Limited, Unit 1, 12/F, International Commerce Center, 1 Austin Road West, Kowloon, Hong Kong.
authors: Ivan
authors: I
authors: Molodtsov
authors: Gero Limited, Unit 1, 12/F, International Commerce Center, 1 Austin Road West, Kowloon, Hong Kong.|Northern (Arctic) Federal University, 163002, Severnaya Dvina Emb. 17, Arkhangelsk, Russian Federation.
authors: Leonid I
authors: LI
authors: Menshikov
authors: Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.|Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: Robert J
authors: RJ
authors: Shmookler Reis
authors: Moscow Institute of Physics and Technology, 141700, Institutskii per. 9, Dolgoprudny, Moscow Region, Russian Federation.|Gero Limited, Unit 1, 12/F, International Commerce Center, 1 Austin Road West, Kowloon, Hong Kong.
authors: Peter
authors: P
authors: Fedichev
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D031204:Caloric Restriction; D004331:Drosophila melanogaster / Q000235:genetics; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D008136:Longevity / Q000235:genetics; D008957:Models, Genetic; D019577:Mole Rats; D025341:Principal Component Analysis; D013312:Stress, Physiological / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics