PAI-1 expression increases with age, and is implicated in cellular senescence, inflammation, and detrimental remodeling of tissue, such as the generation of fibrosis. These line items are all connected, as a burden of lingering senescent cells tissues has been shown to be sufficient to cause the other two, but nothing is biochemistry is ever as simple as it first appears.
PAI-1 in the context of aging has received increased research interest since the discovery of a small population of human loss-of-function mutants who live perhaps 7 years longer their their near neighbor peers. In such small samples numbers should probably be taken with a grain of salt, but the biochemistry suggests that there is something interesting going on under the hood.
In today’s open access paper, researchers report on an investigating of the role of PAI-1 in muscle aging in mice. Interestingly, loss of function is only protective in female mice when it comes to age-related loss of muscle mass and bone mineral density. This is not what one might expect for a protein that has a large effect size on life span and aspects of degenerative aging in other tissues, but nothing is simple in biochemistry.
Roles of plasminogen activator inhibitor-1 in aging-related muscle and bone loss in mice
Aging-related sarcopenia and osteoporosis are musculoskeletal disorders characterized by accelerated muscle and bone loss. Plasminogen activator inhibitor-1 (PAI-1), a fibrinolysis inhibitor, is involved in various pathological conditions, including sarcopenia and osteoporosis; however, its roles in aging-related sarcopenia and osteoporosis have yet to be fully investigated. Therefore, we investigated the roles of PAI-1 in aging-related sarcopenia and osteoporosis using PAI-1-gene-deficient and wild-type mice. Aging-related changes in muscle and bone were assessed by comparing the values in 24-month-old mice to those in 6-month-old mice.
Regardless of sex, differences in muscle and bone parameters were observed between 24-month-old and 6-month-old mice. Aging increased PAI-1 expression in the gastrocnemius and soleus muscles of both female and male mice. PAI-1 deficiency significantly blunted aging-related decreases in lower limb muscle mass, muscle tissue weights, and grip strength in female mice but not in males. Moreover, PAI-1 deficiency significantly blunted aging-related cortical bone loss at the femurs and tibias of female but not male mice. These results indicate that PAI-1 is partly involved in aging-related sarcopenia and osteopenia in female mice, although the corresponding mechanisms remain unknown.
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