image: Figure 5. Aging-related tissue fibrosis in the gastrocnemius muscles of female mice. Picro-Sirius Red-stained cross-sections of the gastrocnemius muscles from 6- and 24-month-old female mice with PAI-1 gene deficiency (PAI-1−/−) and their wild-type counterparts (PAI-1+/+) are shown (A). Photomicrographs of four regions in each muscle section were analyzed, and the mean occupancy of collagen-containing fibrotic areas in tissue sections was calculated (B) (n = 3 in each group). Scale bars = 100 μm. Data are presented as mean ± standard error of the mean. *P < 0.05.
Credit: Copyright: © 2025 Ohira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“These results indicate that PAI-1 is partly involved in aging-related sarcopenia and osteopenia in female mice, although the corresponding mechanisms remain unknown.”
BUFFALO, NY — October 23, 2025 — A new research paper was published in Volume 17, Issue 9 of Aging-US on September 11, 2025, titled “Roles of plasminogen activator inhibitor-1 in aging-related muscle and bone loss in mice.”
In this study led by first author Takashi Ohira and corresponding author Hiroshi Kaji from Kindai University Faculty of Medicine, researchers found that female mice lacking the gene for plasminogen activator inhibitor-1 (PAI-1) were protected from age-related muscle weakness and bone thinning. This suggests that PAI-1 could be a potential target for future treatments to reduce frailty in aging populations.
As the global population continues to age, more people are affected by conditions such as sarcopenia and osteoporosis. These disorders involve the progressive loss of skeletal muscle mass and bone density, leading to reduced mobility, a greater risk of falls, and a lower quality of life.
To investigate the role of PAI-1 in aging, researchers compared young (6-month-old) and aged (24-month-old) male and female mice, with and without the PAI-1 gene. They found that PAI-1 levels increased with age in both sexes. However, only female mice lacking the PAI-1 gene experienced a significant reduction in age-related muscle and bone loss.
Female mice without PAI-1 maintained stronger grip strength and greater muscle mass in their lower limbs. They also showed less cortical bone loss in their femurs and tibias. In contrast, male mice did not experience the same benefits, despite also showing increased levels of PAI-1 with age. These results suggest that PAI-1 contributes to aging-related decline in a sex-specific manner.
“The present study found that lower limb muscle mass, gastrocnemius and soleus muscle tissue weights, and grip strength were significantly lower in 24-month-old male and female wild-type mice than in their 6-month-old counterparts.”
PAI-1 plays key roles in blood clotting, inflammation, and cellular senescence—a process in which aging cells release harmful molecules that affect nearby tissues. One of these molecules, interleukin-6 (IL-6), is a major driver of inflammation. The researchers found that aged female mice lacking PAI-1 had lower IL-6 levels in both muscle and blood, suggesting that PAI-1 may contribute to muscle and bone loss by promoting inflammation. These protective effects were also not associated with changes in muscle protein turnover or reductions in fibrous tissue, reinforcing the idea that PAI-1’s impact is likely driven by inflammatory signaling.
This study highlights PAI-1 as a promising therapeutic target for slowing or preventing age-related declines in muscle and bone health, particularly in women. Since postmenopausal women are especially vulnerable to osteoporosis and frailty, a better understanding of how PAI-1 contributes to aging could lead to new strategies for maintaining strength and mobility in later life. Further research is needed to explore how PAI-1 interacts with other age-related biological changes and why its effects differ between sexes.
DOI: https://doi.org/10.18632/aging.206318
Corresponding author: Hiroshi Kaji — hkaji@med.kindai.ac.jp
Abstract video: https://www.youtube.com/watch?v=hg4qKf-oO2I
Keywords: plasminogen activator inhibitor-1, aging, sarcopenia, osteoporosis, sex
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Roles of plasminogen activator inhibitor-1 in aging-related muscle and bone loss in mice
Article Publication Date
11-Sep-2025
COI Statement
The authors declare no conflicts of interest related to this study.