Two-dimensional gel electrophoretic studies on the cellular aging

Accumulation of alpha-2-macroglobulin in human fibroblasts with aging

T. Kondo, Masakiyo Sakaguchi, M. Namba

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

To understand the mechanisms that control life span and age-related phenotypes, we used two-dimensional (2D) gel electrophoresis to study the intracellular proteins whose amounts change during the process of cellular aging. We found that the amount of an alpha-2-macroglobulin (A2M) fragment derived from culture medium increased in the cells with aging. A2M is linked to Alzheimer's disease both genetically and functionally. This is the first report of accumulation of an A2M fragment in senescent fibroblasts. We also studied 2D gel profiles of human fibroblasts immortalized by treatment with either 60Co gamma rays or 4-nitroquinoline 1-oxide. As immortalized cells overcome cellular senescence to gain an unlimited life span, the proteins whose amounts change after immortalization may be relevant to the age-related phenotypes. 2D gel analysis revealed that the A2M fragment was down-regulated in the immortalized cells, compared with their normal counterparts, regardless of their passage. We also found that the other four proteins increased in amount with aging and decreased in amount after immortalization. Our results suggest: (1) the A2M incorporation into the cells is increased in the process of cellular aging; and (2) A2M may be linked to the age-related phenotypes that were lost during the process of immortalization of human cells.

Original languageEnglish
Pages (from-to)487-495
Number of pages9
JournalExperimental Gerontology
Volume36
Issue number3
DOIs
Publication statusPublished - 2001

Fingerprint

alpha-Macroglobulins
Cell Aging
Fibroblasts
Aging of materials
Gels
Electrophoresis, Gel, Two-Dimensional
Phenotype
4-Nitroquinoline-1-oxide
Proteins
Gamma Rays
Electrophoresis
Gamma rays
Culture Media
Alzheimer Disease
Cells

Keywords

  • alpha-2-Macroglobulin
  • Alzheimer's disease
  • Cellular aging
  • Immortalization of human cells
  • Two-dimensional gel electrophoresis

ASJC Scopus subject areas

  • Ageing
  • Medicine(all)

Cite this

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abstract = "To understand the mechanisms that control life span and age-related phenotypes, we used two-dimensional (2D) gel electrophoresis to study the intracellular proteins whose amounts change during the process of cellular aging. We found that the amount of an alpha-2-macroglobulin (A2M) fragment derived from culture medium increased in the cells with aging. A2M is linked to Alzheimer's disease both genetically and functionally. This is the first report of accumulation of an A2M fragment in senescent fibroblasts. We also studied 2D gel profiles of human fibroblasts immortalized by treatment with either 60Co gamma rays or 4-nitroquinoline 1-oxide. As immortalized cells overcome cellular senescence to gain an unlimited life span, the proteins whose amounts change after immortalization may be relevant to the age-related phenotypes. 2D gel analysis revealed that the A2M fragment was down-regulated in the immortalized cells, compared with their normal counterparts, regardless of their passage. We also found that the other four proteins increased in amount with aging and decreased in amount after immortalization. Our results suggest: (1) the A2M incorporation into the cells is increased in the process of cellular aging; and (2) A2M may be linked to the age-related phenotypes that were lost during the process of immortalization of human cells.",
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