Aging in Mouse Brain Is a Cell/Tissue-Level Phenomenon Exacerbated by Proteasome Loss

Biological aging is often described by its phenotypic effect on individuals. Still, its causes are more likely found on the molecular level. Biological organisms can be considered as reliability-engineered, robust systems and applying reliability theory to their basic nonaging components, proteins,...

Full description

Saved in:
Bibliographic Details
Published inJournal of proteome research Vol. 9; no. 7; pp. 3551 - 3560
Main Authors Mao, Lei, Römer, Irmgard, Nebrich, Grit, Klein, Oliver, Koppelstätter, Andrea, Hin, Sascha C, Hartl, Daniela, Zabel, Claus
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 02.07.2010
Subjects
Aging - metabolism
Analysis of Variance
Animals
Electrophoresis, Gel, Two-Dimensional - methods
Mice
Mice, Inbred C57BL
Proteasome Endopeptidase Complex - metabolism
Proteins - chemistry
Proteome - metabolism
Proteomics - methods
Regression Analysis
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods
proteasome
aging
mouse brain
redundancy
reliability theory
proteome
Online AccessGet full text

Cover

More Information
Summary:Biological aging is often described by its phenotypic effect on individuals. Still, its causes are more likely found on the molecular level. Biological organisms can be considered as reliability-engineered, robust systems and applying reliability theory to their basic nonaging components, proteins, could provide insight into the aging mechanism. Reliability theory suggests that aging is an obligatory trade-off in a fault-tolerant system such as the cell which is constructed based on redundancy design. Aging is the inevitable redundancy loss of functional system components, that is proteins, over time. In our study, we investigated mouse brain development, adulthood, and aging from embryonic day 10 to 100 weeks. We determined redundancy loss of different protein categories with age using reliability theory. We observed a near-linear decrease of protein redundancy during aging. Aging may therefore be a phenotypic manifestation of redundancy loss caused by nonfunctional protein accumulation. This is supported by a loss of proteasome system components faster than dictated by reliability theory. This loss is highly detrimental to biological self-renewal and seems to be a key contributor to aging and therefore could represent a major target for therapies for aging and age-related diseases.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1535-3893
1535-3907
DOI:10.1021/pr100059j