Kl;Pai1

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Genetic mutants with Kl, Pai1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Diet
ad libitum, standard rodent chow diet
Lifespan (days)
163.0
Lifespan comparisons
Double mutant kl(KO);pai-1(KO) has a lifespan of 163.0 days, while single mutant kl(KO) has a lifespan of 58.0 days.
Citation
View abstract
Eren M et al., 2014, PAI-1-regulated extracellular proteolysis governs senescence and survival in Klotho mice. Proc Natl Acad Sci U S A. 111(19):7090-5 24778222 Click here to select all mutants from this PubMed ID in the graph
Abstract
Cellular senescence restricts the proliferative capacity of cells and is accompanied by the production of several proteins, collectively termed the "senescence-messaging secretome" (SMS). As senescent cells accumulate in tissue, local effects of the SMS have been hypothesized to disrupt tissue regenerative capacity. Klotho functions as an aging-suppressor gene, and Klotho-deficient (kl/kl) mice exhibit an accelerated aging-like phenotype that includes a truncated lifespan, arteriosclerosis, and emphysema. Because plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor (SERPIN), is elevated in kl/kl mice and is a critical determinant of replicative senescence in vitro, we hypothesized that a reduction in extracellular proteolytic activity contributes to the accelerated aging-like phenotype of kl/kl mice. Here we show that PAI-1 deficiency retards the development of senescence and protects organ structure and function while prolonging the lifespan of kl/kl mice. These findings indicate that a SERPIN-regulated cell-nonautonomous proteolytic cascade is a critical determinant of senescence in vivo.

Diet
ad libitum, standard rodent chow diet
Lifespan (days)
246.0
Lifespan comparisons
Double mutant kl(KO);pai-1(KO) has a lifespan of 246.0 days, while single mutant kl(KO) has a lifespan of 58.0 days.
Citation
View abstract
Eren M et al., 2014, PAI-1-regulated extracellular proteolysis governs senescence and survival in Klotho mice. Proc Natl Acad Sci U S A. 111(19):7090-5 24778222 Click here to select all mutants from this PubMed ID in the graph
Abstract
Cellular senescence restricts the proliferative capacity of cells and is accompanied by the production of several proteins, collectively termed the "senescence-messaging secretome" (SMS). As senescent cells accumulate in tissue, local effects of the SMS have been hypothesized to disrupt tissue regenerative capacity. Klotho functions as an aging-suppressor gene, and Klotho-deficient (kl/kl) mice exhibit an accelerated aging-like phenotype that includes a truncated lifespan, arteriosclerosis, and emphysema. Because plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor (SERPIN), is elevated in kl/kl mice and is a critical determinant of replicative senescence in vitro, we hypothesized that a reduction in extracellular proteolytic activity contributes to the accelerated aging-like phenotype of kl/kl mice. Here we show that PAI-1 deficiency retards the development of senescence and protects organ structure and function while prolonging the lifespan of kl/kl mice. These findings indicate that a SERPIN-regulated cell-nonautonomous proteolytic cascade is a critical determinant of senescence in vivo.

Search genes: Kl Pai1

Entrez ID
Symbol
GenAge
MGI ID

16591
Kl
View on GenAge (Kl)
MGI:1101771

klotho

Symbol
GenAge

Pai1
View on GenAge (Pai1)

No gene information for Pai1

Orthologs of Kl;Pai1 in SynergyAge

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Orthologs of Kl in SynergyAge

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Orthologs of Pai1 in SynergyAge

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SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.