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.

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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