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The Proteasome and Ageing

Ashok N Hegde1, Lindsey M Duke2, Logan E Timm2

  • 1Department of Biological and Environmental Sciences, Georgia College and State University, Milledgeville, GA, USA. ashok.hegde@gcsu.edu.

Sub-Cellular Biochemistry
|January 4, 2023
PubMed

Insights

The proteasome, a cellular complex, degrades damaged proteins but declines with age, leading to protein accumulation. This decline may link to aging and neurodegenerative diseases, impacting longevity.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biogerontology

Background:

  • The proteasome is a vital cellular complex responsible for degrading proteins, essential for both normal physiological regulation and cellular protection against damage.
  • Protein damage can arise from internal sources (e.g., reactive oxygen species) and external factors (e.g., UV radiation), with the proteasome playing a key role in eliminating these damaged proteins.
  • With advancing age, the proteasome's efficiency in degrading damaged proteins diminishes, a phenomenon observed across various tissues.

Purpose of the Study:

  • To review the multifaceted roles of the proteasome in the aging process.
  • To examine the evidence linking proteasome function and dysfunction to age-related cellular changes and diseases.
  • To explore the potential connection between proteasome activity and longevity.

Main Methods:

  • Review of existing literature on proteasome function in aging.
  • Analysis of studies investigating proteasome activity in cultured cells.
  • Examination of data from model organisms and human studies on aging and proteasome function.

Main Results:

  • Age-related decline in proteasome catalytic activity and altered subunit expression are evident in muscle, skin, and brain tissues.
  • Reduced proteasome function contributes to the accumulation of damaged and misfolded proteins.
  • Impaired proteasome activity is implicated in age-related neurodegenerative diseases and the pathology of protein aggregate formation.

Conclusions:

  • Proteasome dysfunction is a significant factor in the aging process, contributing to cellular damage and disease.
  • Deficits in proteasome activity may underlie the accumulation of aberrant proteins, a hallmark of aging and neurodegeneration.
  • Evidence suggests a correlation between proteasome function and lifespan, highlighting its importance in longevity.
Keywords:
LongevityMisfolded proteinsNeurodegenerationOxidative damageProtein degradationProteolysisProteostasisSenescenceUbiquitin

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