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No effect of aging on skeletal muscle insulin-like growth factor mRNAs
M T Hamilton1, D R Marsh, D S Criswell
1Department of Integrative Biology, University of Texas Medical School, Houston 77030, USA.
Abstract:
This study examined the hypothesis that during aging insulin-like growth factor (IGF) mRNAs are reduced in skeletal muscle. IGF-I, IGF-II, and IGF-binding protein-5 (IGFBP-5) mRNAs were measured with a ribonuclease protection assay in the gastrocnemius of specific pathogen-free Fischer-344 rats. We hypothesized that IGF-I, IGF-II, and IGFBP-5 mRNA concentration (normalized to 18S RNA) in the gastrocnemius muscle of growing animals (3 mo) would be downregulated in a coordinated manner with muscle size during aging-associated atrophy. As indicated by muscle wet weight and total protein content, the gastrocnemius muscle was growing in the 3-mo group (P < 0.01 smaller compared with 12 mo), fully developed at 12 mo, and was atrophied at 24 mo of age (P < 0.05 compared with 12 mo). IGF-I mRNA concentration in the gastrocnemius of 12- and 24-mo-old rats was 39-49% less than in 3-mo-old rats (P < 0.05). Contrary to our hypothesis, there was not a significant skeletal muscle IGF-I mRNA difference between middle age (12 mo) and senescence (24 mo). Thus IGF-I mRNA changed during maturation (3-12 mo) but not during aging (12-24 mo). Skeletal muscle IGF-II mRNA concentration was not different among 3-, 12-, and 24-mo-old animals. Furthermore, animal age did not have an effect on IGFBP-5 mRNA concentration. We conclude that the aging-associated atrophy of skeletal muscle is not caused by altered pretranslational regulation of IGF-I, IGF-II, or IGFBP-5 in skeletal muscle.
Insights
Aging skeletal muscle atrophy is not caused by changes in insulin-like growth factor (IGF) mRNA levels. This study found no significant differences in IGF-I, IGF-II, or IGFBP-5 mRNA between middle-aged and old rats.
Area of Science:
- Molecular Biology
- Aging Research
- Skeletal Muscle Physiology
Background:
- Skeletal muscle atrophy is a hallmark of aging.
- Insulin-like growth factors (IGFs) play a role in muscle growth and maintenance.
- Previous research suggested IGF mRNA may decrease with age.
Purpose of the Study:
- To investigate the hypothesis that aging reduces insulin-like growth factor (IGF) mRNAs in skeletal muscle.
- To determine if IGF-I, IGF-II, and IGFBP-5 mRNA levels correlate with age-related muscle atrophy.
- To examine the pretranslational regulation of IGFs during skeletal muscle aging.
Main Methods:
- Measurement of IGF-I, IGF-II, and IGFBP-5 mRNA concentrations in rat gastrocnemius muscle using ribonuclease protection assay.
- Normalization of mRNA levels to 18S RNA.
- Comparison of mRNA levels across different age groups: 3 months (growing), 12 months (mature), and 24 months (aged).
Main Results:
- IGF-I mRNA was significantly lower in 12- and 24-month-old rats compared to 3-month-old rats, indicating changes during maturation but not aging.
- No significant difference in IGF-I mRNA was observed between middle-aged (12 months) and senescent (24 months) rats.
- Skeletal muscle IGF-II and IGFBP-5 mRNA concentrations did not differ significantly across the studied age groups.
Conclusions:
- Aging-associated skeletal muscle atrophy is not caused by altered pretranslational regulation of IGF-I, IGF-II, or IGFBP-5.
- IGF-I mRNA levels change during muscle maturation but not during the aging process from middle age to senescence.
- The findings do not support the hypothesis that reduced IGF mRNA is the primary driver of age-related muscle atrophy.