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GPCR systems coordinate cellular resilience against aging-associated stress.

Tabitha Boeringer1, Mia Pardo1, Carter J Craig1

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Cellular damage causes aging diseases, but G protein-coupled receptors (GPCRs) help resilience. Stable GPCR complexes, called receptorsomes, act as hubs to sense and mitigate stress, potentially delaying aging pathologies.

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G protein-coupled receptoradaptoragingallostasisresiliencestresstherapeutic

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Area of Science:

  • Cellular biology
  • Molecular medicine
  • Aging research

Background:

  • Aging is linked to cumulative cellular damage from various stressors.
  • G protein-coupled receptors (GPCRs) are crucial for cellular stress resilience.
  • Existing research highlights GPCRs' role in cellular defense mechanisms.

Purpose of the Study:

  • To introduce the concept of "receptorsomes" as stable GPCR complexes.
  • To explore how receptorsomes integrate and mitigate stress across cellular compartments.
  • To link receptosome composition to aging hallmarks and stress responses.

Main Methods:

  • Literature review synthesizing evidence on GPCR complexes and stress.
  • Analysis of receptosome composition and its role in cellular resilience.
  • Mapping receptosome functions to specific aging hallmarks and stress types (oxidative, proteostatic, hypoxic).

Main Results:

  • Receptorsomes are proposed as adaptive hubs comprising GPCRs and specific adaptors (e.g., β-arrestins, GIT2, RGS proteins, ASK1, YAP/TAZ).
  • These complexes enable G protein-independent signaling for stress detection, damage repair, and homeostasis.
  • Receptosome composition is linked to cellular responses against diverse stressors relevant to aging.

Conclusions:

  • Receptorsomes represent a novel framework for understanding cellular adaptation to stress.
  • Therapeutic modulation of receptosome adaptors may enhance resilience and health span.
  • Targeting receptorsomes offers a potential strategy to delay age-related diseases and promote longevity.