Related Experiment Video

Updated: Feb 10, 2026

A Flow Cytometry-Based Cytotoxicity Assay for the Assessment of Human NK Cell Activity
06:08

A Flow Cytometry-Based Cytotoxicity Assay for the Assessment of Human NK Cell Activity

Published on: August 9, 2017

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Overactivation of Cdc42 GTPase Impairs the Cytotoxic Function of NK Cells From Old Individuals Towards Senescent

Albert Kallon Koroma1,2, Karmveer Singh1,2, Yongfang Wang1

  • 1Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany.

Aging Cell
|February 8, 2026
PubMed

Insights

Aging impairs natural killer (NK) cells, hindering their ability to clear senescent fibroblasts. This dysfunction stems from elevated Cdc42 activity, which can be targeted to restore NK cell function and combat age-related diseases.

Area of Science:

  • Immunology
  • Cell Biology
  • Gerontology

Background:

  • Senescent fibroblasts accumulate with age, contributing to organ aging and related diseases.
  • Natural killer (NK) cells are crucial for clearing senescent cells, but their function declines with age.
  • Mechanisms behind age-related NK cell dysfunction and senescent cell accumulation are not fully understood.

Purpose of the Study:

  • Investigate the mechanisms behind impaired NK cell function in aging.
  • Determine the role of NK cells in clearing senescent fibroblasts in aged individuals.
  • Identify potential therapeutic targets to restore NK cell function in aging.

Main Methods:

  • Compared NK cell function in young and old adults/mice.
  • Assessed perforin and granzyme B release from NK cells.
  • Analyzed Cdc42 Rho GTPase activation and its effect on microtubular organization.
  • Utilized CASIN, a Cdc42 inhibitor, to evaluate its impact on aged NK cell function.

Main Results:

  • Aged NK cells exhibit reduced ability to clear senescent fibroblasts due to impaired perforin and granzyme B release.
  • Elevated Cdc42 activity in aged NK cells disrupts microtubular organization, hindering cytotoxic granule release and energy homeostasis.
  • Inhibition of Cdc42 with CASIN restored NK cell function, improving cytotoxic capacity against senescent cells.

Conclusions:

  • Dysfunctional NK cells, characterized by impaired cytotoxic granule release due to elevated Cdc42 activity, contribute to senescent fibroblast accumulation in aging.
  • Targeting Cdc42 offers a promising therapeutic strategy to rejuvenate NK cell function and combat age-related diseases driven by senescent cells.
Keywords:
CASINCdc42NK cellaginggranzyme Bmalignant lymphoma cellsperforinsenescent fibroblasts

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