image: Figure 1. Arg-ii-/- mice reveal improved physical activity in aging. Diurnal voluntary physical activities (as revolution/hour on an average of 7 days in the wheel running cages under 12:12 light-dark conditions: 0-12, light-on (resting phase, white bar); 12–24, light-off (active phase, black bar) of young and old wild type (wt) and arg-ii-/- (ko) male (A–C) and female mice (D–F). (A, D) General activities of wheel running in males and females respectively; (B, E) Quantification of the general or total wheel-running activities during light-on and light-off in males and females, respectively. Graphs show the counting of total wheel revolutions during 24 hours in the young and old wt and ko mice. (C, F) Graphs show wheel running activities during light-on (white bar) and light-off (black bar) in males and females, respectively. Data are reported as means ± SEM. Combined one-way ANOVA and unpaired t-test with Welch’s correction were applied. n = 4 to 5 mice for each group. (G) Non-voluntary physical activities (treadmill fatigue test) in old male and female wt and arg-ii-/- mice. A parametric unpaired t-test with Welch’s correction was applied. n = 5 animals for each group. *p < 0.05. (H) Body weight in old male and female wt and arg-ii-/- mice. One-way ANOVA was applied with n = 5 animals for each group. ***p < 0.001. (I) Traction test measuring the success rate of lifting their weight to lean all the paws on a horizontally suspended bar. A contingency test was performed with n = 11–12 mice for each group. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 between the indicated groups.
Credit: © 2024 Caretti et al.
“Our results suggest that increased Arg-II in non-skeletal muscle cells promotes age-associated sarcopenia, particularly in male mice.”
BUFFALO, NY- January 22, 2025 – A new research paper was published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) on December 12, 2024, Volume 16, Issue 22, titled “Arginase-II gene deficiency reduces skeletal muscle aging in mice.”
Researchers Matteo Caretti, Duilio Michele Potenza, Guillaume Ajalbert, Urs Albrecht, Xiu-Fen Ming, Andrea Brenna, and Zhihong Yang from the University of Fribourg found that removing a specific gene, called arginase-II (Arg-II), can slow down muscle aging in mice. Their research showed that older mice lacking this gene stayed more active and had healthier skeletal muscles compared to normal aging mice. This discovery could lead to new treatments to help people maintain muscle strength and mobility as they become older.
As people age, their muscles naturally get weaker, leading to reduced physical activity and overall quality of life. This condition, known as sarcopenia, occurs because of muscle fiber loss, inflammation, and scar tissue buildup. The study found that the Arg-II gene contributes to this process.
The research team compared normal mice with mice lacking the Arg-II gene and discovered that in general, the mice without the gene had improved muscle health, reduced inflammation, and fewer signs of age-related muscle decline. It was also found that older male mice deficient in the Arg-II gene were more active, particularly during their peak nighttime activity. These mice had stronger muscles and performed better in physical tests. Interestingly, the benefits of Arg-II gene removal were more pronounced in male mice compared to females, suggesting that hormonal or genetic differences might play a role in age-related muscle loss.
“The improved phenotype of arg-ii-/- mice in aging is associated with reduced sarcopenia, cellular senescence, inflammation, and fibrosis, whereas age-associated decline of microvascular endothelial cell density, satellite cell numbers, and muscle fiber types in skeletal muscle is prevented in arg-ii-/- mice.”
ARG-II protein was not found in muscle fibers but instead in surrounding cells such as fibroblasts and blood vessel cells, which makes scientists believe this gene influences muscle aging indirectly. Independently of that, the findings suggest that targeting the Arg-II gene could help slow down age-related muscle deterioration and improve muscle function in older adults.
“[…] we demonstrate an increased arg-ii gene expression level in aging skeletal muscle and found Arg-II protein expression in endothelial cells and fibroblasts, but not in skeletal muscle fibers, macrophages, and satellite cells.”
While these results are promising, further research is needed to determine whether blocking the Arg-II gene in humans could provide similar benefits. Furthermore, understanding why male and female mice responded differently to the gene removal will be essential before personalized treatments for age-related muscle loss. If future studies confirm these findings in humans, targeting Arg-II could become a valuable strategy to help adults maintain muscle strength, mobility, and overall quality of life as they age.
Read the full paper: DOI: https://doi.org/10.18632/aging.206173
Corresponding authors: Andrea Brenna – andrea.brenna@unifr.ch, and Zhihong Yang – zhihong.yang@unifr.ch
Keywords: aging, arginase-II, cellular senescence, fibrosis, physical activity, skeletal muscle
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About Aging:
The journal Aging aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Arginase-II gene deficiency reduces skeletal muscle aging in mice
Article Publication Date
12-Dec-2024
COI Statement
The authors declare there are no conflicts of interest related to this study.