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Proteostasis in T cell aging.

A Elisabeth Gressler1, Houfu Leng2, Heidi Zinecker3

  • 1Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Str. 10, 13125 Berlin, Germany.

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|September 14, 2023
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Summary

Aging impairs T cell function by disrupting proteostasis, the balance of proteins within cells. This review explores how this decline affects immunity and discusses interventions to rejuvenate aging T cells.

Keywords:
AgingDegradationInflamm-agingProteostasisT cellTranslation

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Area of Science:

  • Immunology
  • Cellular Biology
  • Gerontology

Background:

  • Aging causes immune cell dysfunction, increasing susceptibility to infections and age-related diseases.
  • T cells, crucial for adaptive immunity, exhibit reduced function with age, potentially due to impaired proteostasis.
  • Proteostasis, the maintenance of a stable proteome, involves protein synthesis, quality control, and degradation pathways.

Purpose of the Study:

  • To review molecular mechanisms affecting proteostasis in T cells during aging.
  • To elucidate the consequences of compromised T cell proteostasis on immune function and inflamm-aging.
  • To discuss strategies for improving proteostasis and rejuvenating aged T cells.

Main Methods:

  • Literature review focusing on molecular processes impacting T cell proteostasis.
  • Analysis of functional and quantitative changes in proteostasis pathways with aging.
  • Synthesis of data on the biological outcomes of impaired T cell proteostasis.

Main Results:

  • Aging disrupts T cell proteostasis through alterations in protein synthesis, folding, and degradation.
  • Compromised proteostasis leads to impaired T cell activation, reduced effector functions, and enhanced inflamm-aging.
  • Specific molecular pathways affected include the proteasome, autophagy, and lysosomal degradation.

Conclusions:

  • Disturbed proteostasis is a key driver of age-related T cell decline.
  • Restoring proteostasis holds promise for enhancing immune function in the elderly.
  • Pharmacological and physical interventions targeting proteostasis pathways may rejuvenate aged T cells.