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Updated: Jun 5, 2025

Imaging and Quantifying Mitochondrial Morphology in C. elegans During Aging
Published on: January 17, 2025
Ageing drop by drop: Disturbance of the membrane-less organelle biogenesis as an aging hallmark
Baraa M G A Saqr1, Nikolay O Kotoyants1, Semen V Nesterov2
1Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Institutskiy pereulok, 9, Dolgoprudny, 141700, Russia.
Abstract:
Despite extensive research, the features associated with the aging phenotype are not all-inclusive and need to be updated on a regular basis to incorporate new findings. We propose to include the dysfunction of membrane-less organelle (MLO) as a new aging hallmark. Special scaffold proteins with a high degree of intrinsic disorder drive the formation of MLOs via the liquid-liquid phase separation (LLPS) process. Aberrant behavior of MLOs was shown to be associated with the pathogenesis of many neurodegenerative diseases. In this work, we challenge the aging through bidirectional bioinformatics analysis of human proteins found in Granulome consisting of 7264 protein and Ageome containing 1624 aging-related proteins. The analysis indicates the interconnectivity of MLOs and aging. Approximately 67 % of the Ageome are presented in Granulome thereby constituting the Intersectome that include 1084 proteins showing an enrichment significantly higher than for the random datasets of the same size. Furthermore, for proteins in 10 representative MLOs, we analyzed in detail molecular functions, association with the already known aging hallmarks, and the roles in MLO formation (scaffold, client, or regulator). Cumulatively, our results strengthen the hypothesis that the dysfunction of MLOs can serve as a potent new aging hallmark.
Insights
Dysfunctional membrane-less organelles (MLOs) are proposed as a new aging hallmark. Bioinformatics analysis reveals significant overlap between MLO proteins and aging-related proteins, supporting this hypothesis.
Area of Science:
- Biogerontology
- Molecular and Cellular Biology
- Bioinformatics
Background:
- Aging hallmarks require regular updates with new scientific findings.
- Membrane-less organelles (MLOs) form via liquid-liquid phase separation (LLPS) and are implicated in neurodegenerative diseases.
- Scaffold proteins with intrinsic disorder are key to MLO formation.
Purpose of the Study:
- To investigate the potential of MLO dysfunction as a novel hallmark of aging.
- To analyze the relationship between proteins involved in MLOs and known aging-related proteins.
Main Methods:
- Bidirectional bioinformatics analysis of human proteins from Granulome (7264 proteins) and Ageome (1624 proteins).
- Identification and analysis of the 'Intersectome' of proteins common to both datasets.
- Detailed analysis of molecular functions and roles of proteins within 10 representative MLOs.
Main Results:
- A significant overlap (67%) was found between Ageome and Granulome proteins, forming an 'Intersectome' of 1084 proteins.
- The Intersectome showed significantly higher enrichment than random datasets.
- Proteins within 10 MLOs were analyzed for their functions, links to aging, and roles in MLO formation.
Conclusions:
- The study provides strong evidence supporting the dysfunction of MLOs as a potential new hallmark of aging.
- The interconnectivity between MLOs and aging processes is highlighted.
- Further research into MLOs could offer new insights into aging mechanisms and age-related diseases.
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