Identification of long-lived proteins reveals exceptional stability of essential cellular structures

Cell. 2013 Aug 29;154(5):971-982. doi: 10.1016/j.cell.2013.07.037.


Intracellular proteins with long lifespans have recently been linked to age-dependent defects, ranging from decreased fertility to the functional decline of neurons. Why long-lived proteins exist in metabolically active cellular environments and how they are maintained over time remains poorly understood. Here, we provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complexes (NPCs) are maintained over a cell's life through slow but finite exchange of even its most stable subcomplexes. This maintenance is limited, however, as some nucleoporin levels decrease during aging, providing a rationale for the previously observed age-dependent deterioration of NPC function. Our identification of a long-lived proteome reveals cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process. PAPERCLIP:

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology*
  • Brain / metabolism
  • Cellular Senescence*
  • Neuroglia / metabolism
  • Neurons / metabolism
  • Nuclear Pore / metabolism
  • Nuclear Pore Complex Proteins / metabolism*
  • Protein Biosynthesis
  • Proteome / metabolism*
  • Rats


  • Nuclear Pore Complex Proteins
  • Proteome