MicroRNA Dynamics in Aging and Age-Related Diseases

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the post-transcriptional level and have emerged as central orchestrators of ageing and age-related diseases. Their levels shift dynamically across tissues, circulation and extracellular vesicles, reflecting both systemic and organ-specific processes. In model organisms, miRNAs influence pathways such as autophagy, proteostasis and inter-tissue signalling, while human studies link specific circulating miRNA signatures to cardiovascular, neurodegenerative and metabolic disorders. Understanding these dynamics unveils the molecular drivers of ageing, informs minimally invasive biomarker development and points towards innovative therapeutic strategies.

Research from Nature Portfolio

Recent studies have generated comprehensive maps of noncoding RNA expression across multiple organs in ageing and rejuvenated mice, identifying a core set of broadly deregulated miRNAs. Among these, miR-29c-3p emerged as a systemic regulator, its restoration by heterochronic parabiosis aligning aged tissues with youthful profiles and implicating extracellular matrix remodelling pathways in rejuvenation. In a parallel investigation using Caenorhabditis elegans, age-dependent miRNAomic profiling of isolated tissues and extracellular vesicles revealed extensive inter-tissue trafficking. Notably, muscle-derived mir-1 modulates the DAF-16/FOXO longevity axis in the intestine, exemplifying miRNA-mediated inter-organ communication. Foundational blood profiling in healthy and diseased cohorts uncovered nonlinear, age-linked shifts in miRNA abundance and mature strand usage, establishing a framework for age-specific disease biomarkers.

MicroRNA Dynamics in Aging and Age-Related Diseases publication trend

The graph below shows the total number of articles in microrna dynamics in aging and age-related diseases across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): Short noncoding RNA (∼22 nucleotides) that binds target mRNAs to repress translation or promote degradation.

Extracellular vesicle (EV): Membrane-bound particle released by cells carrying proteins, lipids and nucleic acids, including miRNAs, to mediate intercellular communication.

Heterochronic parabiosis: Experimental technique connecting the circulatory systems of young and old animals to study systemic factors in ageing and rejuvenation.

DAF-16/FOXO: Conserved transcription factor regulating stress resistance and longevity, modulated by insulin/IGF-1 signalling and miRNA activity.

Multimorbidity: Co-existence of two or more chronic conditions in one individual, often complicating biomarker interpretation in ageing research.

References

1. Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues. Nature Biotechnology (2023).
2. Tissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans. Nature Communications (2024).
3. Elucidation of how the Mir-23-27-24 cluster regulates development and aging. Experimental & Molecular Medicine (2024).
4. Low circulating levels of miR-17 and miR-126-3p are associated with increased mortality risk in geriatric hospitalized patients affected by cardiovascular multimorbidity. GeroScience (2023).
5. Common diseases alter the physiological age-related blood microRNA profile. Nature Communications (2020).