Surreal illustration of muscle fibers with microRNA strands, symbolizing the fight against muscle aging.

Unlocking the Secrets of Aging: Can MicroRNA Hold the Key to Muscle Health?

Elliot Brynn in Health & Wellness December 2025 • 5 min read.

"New research sheds light on how non-coding RNAs impact age-related muscle decline, offering potential pathways for future therapies."

Maintaining muscle mass and function is crucial for overall health and mobility as we age. However, as we get older, our muscles naturally decline, leading to reduced strength, slower movement, and increased risk of falls. This age-related muscle loss, known as sarcopenia, is a significant health concern, but scientists are working hard to understand its causes and develop effective treatments.

Recent research has focused on the role of small molecules called microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in regulating muscle development and function. These molecules don't code for proteins but instead fine-tune gene expression, influencing a wide range of cellular processes. Understanding how miRNAs and lncRNAs change with age could provide valuable insights into the mechanisms behind sarcopenia and potential targets for intervention.

A new study published in Frontiers in Genetics investigates the expression of miRNAs and lncRNAs in the skeletal muscle of mice from early growth to old age. The findings reveal striking dysregulation of a specific genomic region called the Callipyge locus, suggesting a potential new pathway for age-related muscle decline. Let's delve into this research and explore its implications for future strategies to promote healthy aging.

How Do MicroRNAs and Long Non-Coding RNAs Influence Muscle Aging?

Surreal illustration of muscle fibers with microRNA strands, symbolizing the fight against muscle aging.

MicroRNAs (miRNAs) play a vital role in skeletal muscle development, controlling muscle mass, function, and metabolism throughout life. Long non-coding RNAs (lncRNAs) are also emerging as key players in muscle regulation. This study builds upon previous research that mapped the expression patterns and potential functions of 768 miRNAs in the quadriceps muscle of young mice. Researchers extended this investigation to include 28-month-old mice to identify age-related changes in miRNA and lncRNA expression.

The study revealed that twelve miRNAs were significantly downregulated in the older mice compared to younger ones. Interestingly, ten of these miRNAs were clustered at the Dlk1-Dio3 locus, also known as the 'Callipyge' region. This region is known to influence muscle development and hypertrophy (muscle growth). The collective downregulation of these miRNAs was accompanied by decreased expression of the maternally expressed imprinted LncRNA coding genes Meg3 and Rian, which also originate from the same chromosomal region.

Here's a breakdown of the key findings:

Downregulation of miRNAs: Twelve miRNAs were significantly reduced in older muscle, with ten clustering at the Dlk1-Dio3 locus.
Decreased LncRNA expression: The maternally expressed genes Meg3 and Rian also showed reduced expression with age.
Preserved expression of some LncRNAs: The paternally expressed Dlk1-Dio3 locus members (Rtll, Dio3, and Dlk1) and muscle-related IncRNAs (IncMyoD1, Neat_v1, Neat_v2, and Malatl) remained relatively stable with age, suggesting their roles are more critical during early development.

In contrast, the study found that other lncRNAs related to muscle function, such as IncMyoD1, Neat_v1, Neat_v2 and Malatl, experienced changes during growth but remained stable after 12 weeks, suggesting their importance is mainly limited to the early stages of muscle development and growth. These findings suggest that the Dlk1-Dio3 locus, particularly the maternally expressed genes, could play a critical role in age-related muscle decline.

What Does This Mean for the Future of Muscle Health?

This research provides a valuable step towards understanding the complex mechanisms that govern muscle aging. By identifying the dysregulation of the Dlk1-Dio3 locus and specific miRNAs and lncRNAs, scientists have opened new avenues for potential therapeutic interventions. Future studies could focus on targeting these molecules to prevent or reverse age-related muscle decline, ultimately promoting healthier and more active lives for older adults. While more research is needed, these findings offer hope for developing effective strategies to combat sarcopenia and enhance longevity.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3389/fgene.2018.00548, Alternate LINK

Title: Microrna And Long Non-Coding Rna Regulation In Skeletal Muscle From Growth To Old Age Shows Striking Dysregulation Of The Callipyge Locus

Subject: Genetics (clinical)

Journal: Frontiers in Genetics

Publisher: Frontiers Media SA

Authors: Jasmine Mikovic, Kate Sadler, Lauren Butchart, Sarah Voisin, Frederico Gerlinger-Romero, Paul Della Gatta, Miranda D. Grounds, Séverine Lamon

Published: 2018-11-16

Everything You Need To Know

What are microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and what role do they play in muscle aging?

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are small molecules that don't code for proteins but fine-tune gene expression, influencing many cellular processes. In muscle aging, specific miRNAs and lncRNAs regulate muscle development, function, and metabolism. The study highlights that changes in the expression of these molecules, particularly those related to the Dlk1-Dio3 locus, are associated with age-related muscle decline. Further research could explore how these molecules interact with other factors influencing muscle health, such as protein synthesis rates and degradation pathways.

How does the dysregulation of the Callipyge locus (Dlk1-Dio3) contribute to age-related muscle decline, according to the research?

The study indicates that the Callipyge locus, also known as the Dlk1-Dio3 locus, shows striking dysregulation in aged muscle tissue. Specifically, several miRNAs clustered at this locus are significantly downregulated in older mice. This downregulation is accompanied by decreased expression of the maternally expressed genes Meg3 and Rian, which originate from the same chromosomal region. Since this genomic region is known to influence muscle development and hypertrophy, changes here could be a crucial factor in age-related muscle decline, but understanding the full scope of the locus function requires further study of the interplay between other genomic regions and environmental factors.

The research mentions IncMyoD1, Neat_v1, Neat_v2 and Malatl. What role do these specific lncRNAs play in muscle development, and how does their behavior change with age?

The lncRNAs IncMyoD1, Neat_v1, Neat_v2, and Malatl, are related to muscle function. These lncRNAs experience changes during growth, but their expression remains relatively stable after 12 weeks. This suggests their roles are more critical during the early stages of muscle development and growth, rather than in later stages of aging. These findings highlight the dynamic nature of gene regulation during different life stages, and suggest the importance of understanding the specific timing of molecular events to design effective therapies for age-related conditions.

What potential therapeutic avenues are opened by identifying the dysregulation of the Dlk1-Dio3 locus and specific miRNAs and lncRNAs in the context of muscle aging?

Identifying the dysregulation of the Dlk1-Dio3 locus and specific miRNAs and lncRNAs provides new potential therapeutic avenues for age-related muscle decline. By targeting these molecules, it might be possible to prevent or reverse sarcopenia. Future studies could focus on developing interventions that restore the normal expression patterns of these miRNAs and lncRNAs, potentially leading to healthier and more active lives for older adults. Further studies must consider how the modulation of miRNAs and lncRNAs interact with other potential therapeutic strategies, such as exercise and nutrition.

The study focuses on miRNAs and lncRNAs. How do other factors, such as protein synthesis, degradation pathways, and hormonal changes, interplay with these non-coding RNAs to affect muscle aging, and why is this important?

While the research highlights the role of miRNAs and lncRNAs in muscle aging, it's crucial to recognize that other factors also contribute. Protein synthesis and degradation pathways, hormonal changes, and cellular senescence all interact with these non-coding RNAs to influence muscle health. A comprehensive understanding of muscle aging requires considering all these factors. Furthermore, understanding the interplay between these factors could reveal synergistic therapeutic targets, where combining multiple interventions yields greater benefits than addressing individual pathways in isolation.