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MicroRNAs in Age-Related Proteostasis and Stress Responses
1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Aging is associated with the accumulation of damaged and misfolded proteins through a decline in the protein homeostasis (proteostasis) machinery, leading to various age-associated protein misfolding diseases such as Huntington's or Parkinson's. The efficiency of cellular stress response pathways also weakens with age, further contributing to the failure to maintain proteostasis. MicroRNAs (miRNAs or miRs) are a class of small, non-coding RNAs (ncRNAs) that bind target messenger RNAs at their 3'UTR, resulting in the post-transcriptional repression of gene expression. From the discovery of aging roles for lin-4 in C. elegans, the role of numerous miRNAs in controlling the aging process has been uncovered in different organisms. Recent studies have also shown that miRNAs regulate different components of proteostasis machinery as well as cellular response pathways to proteotoxic stress, some of which are very important during aging or in age-related pathologies. Here, we present a review of these findings, highlighting the role of individual miRNAs in age-associated protein folding and degradation across different organisms. We also broadly summarize the relationships between miRNAs and organelle-specific stress response pathways during aging and in various age-associated diseases.
Insights
MicroRNAs (miRNAs) are crucial regulators of protein homeostasis, a process that declines with aging. This review highlights how miRNAs impact protein folding and degradation, offering insights into age-related diseases.
Area of Science:
- Molecular Biology
- Genetics
- Aging Research
Background:
- Aging leads to decreased protein homeostasis (proteostasis) and accumulation of misfolded proteins.
- Impaired cellular stress responses exacerbate proteostasis failure in aging.
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression post-transcriptionally.
Purpose of the Study:
- To review the role of miRNAs in regulating protein folding and degradation during aging.
- To summarize the connection between miRNAs and organelle-specific stress responses in aging and disease.
Main Methods:
- Literature review of studies on miRNAs, aging, and proteostasis.
- Analysis of findings across different organisms and age-associated pathologies.
Main Results:
- Numerous miRNAs have been identified as key regulators of the aging process.
- miRNAs modulate components of the proteostasis machinery and cellular stress responses.
- Specific miRNAs influence protein folding, degradation, and organelle stress pathways relevant to aging.
Conclusions:
- miRNAs play a significant role in maintaining or failing proteostasis during aging.
- Understanding miRNA functions provides insights into age-related protein misfolding diseases.
- miRNA-mediated regulation of stress responses is critical in aging and associated pathologies.
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