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Stability analysis of a model gene network links aging, stress resistance, and negligible senescence.

Kogan V, Molodtsov I, Menshikov LI, Shmookler Reis RJ, Fedichev P - Sci Rep (2015)

Bottom Line: 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.We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable.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.

View Article: PubMed Central - PubMed

Affiliation: Moscow Institute of Physics and Technology, 141700, Institutskii per. 9, Dolgoprudny, Moscow Region, Russian Federation.

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.

No MeSH data available.


Related in: MedlinePlus

Stability diagram of the model gene network.Below the separatrix defined by Eq. (6) the solutions of Eqs. (1,2) are unstable and correspond to “normally” aging animals. The stable solutions exist above the separatrix and may describe “negligible senescence”.
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f4: Stability diagram of the model gene network.Below the separatrix defined by Eq. (6) the solutions of Eqs. (1,2) are unstable and correspond to “normally” aging animals. The stable solutions exist above the separatrix and may describe “negligible senescence”.

Mentions: and are always real. Both values are negative and hence correspond to stable solutions, provided the genome and the proteome-maintenance system efficiencies are sufficiently high. This corresponds to area above the phase boundary, the separatrix line βpGK/cδ = 1, on the stability diagram (see Fig. 4).


Stability analysis of a model gene network links aging, stress resistance, and negligible senescence.

Kogan V, Molodtsov I, Menshikov LI, Shmookler Reis RJ, Fedichev P - Sci Rep (2015)

Stability diagram of the model gene network.Below the separatrix defined by Eq. (6) the solutions of Eqs. (1,2) are unstable and correspond to “normally” aging animals. The stable solutions exist above the separatrix and may describe “negligible senescence”.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4551969&req=5

f4: Stability diagram of the model gene network.Below the separatrix defined by Eq. (6) the solutions of Eqs. (1,2) are unstable and correspond to “normally” aging animals. The stable solutions exist above the separatrix and may describe “negligible senescence”.
Mentions: and are always real. Both values are negative and hence correspond to stable solutions, provided the genome and the proteome-maintenance system efficiencies are sufficiently high. This corresponds to area above the phase boundary, the separatrix line βpGK/cδ = 1, on the stability diagram (see Fig. 4).

Bottom Line: 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.We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable.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.

View Article: PubMed Central - PubMed

Affiliation: Moscow Institute of Physics and Technology, 141700, Institutskii per. 9, Dolgoprudny, Moscow Region, Russian Federation.

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.

No MeSH data available.


Related in: MedlinePlus