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Increased resistance of lipofuscin-loaded prematurely senescent fibroblasts to starvation-induced programmed cell death

Overview of attention for article published in Biogerontology, July 2006
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Title
Increased resistance of lipofuscin-loaded prematurely senescent fibroblasts to starvation-induced programmed cell death
Published in
Biogerontology, July 2006
DOI 10.1007/s10522-006-9029-7
Pubmed ID
Authors

Yuri Stroikin, Uno Johansson, Sofia Asplund, Karin Öllinger

Abstract

Alterations of cellular structures often found in ageing cells is mainly the result of production of reactive oxygen species and a consequence of aerobic life. Both oxidative stress and decreased degradative capacity of lysosomal system cause accumulation of intralysosomal age-related pigment called lipofuscin. To investigate the influence of lipofuscin on cell function, we compared survival of lipofuscin-loaded and control human fibroblasts following complete starvation induced by exposure to phosphate-buffered saline (PBS). Starving of control fibroblasts resulted in lysosomal alkalinisation, relocation of cathepsin D to the cytosol, caspase-3 activation and, finally, cell death, which became evident 72 h after the start of exposure to PBS. Increase of lysosomal pH was significantly less prominent in lipofuscin-loaded cells than in controls and was accompanied neither by leakage of cathepsin D nor by caspase-3 activation even 96 h after the initiation of starvation. Suppression of autophagy by 3-methyladenine (3-MA) accelerated cell death, while inhibition of cathepsin D delayed it, implying an important role of autophagy in cell survival during starvation and showing the involvement of lysosomes in starvation-induced cell death. Disturbed apoptotic response found in lipofuscin-loaded cells can be interpreted as an example of hormesis--an adaptation to low doses of otherwise harmful agents, in this case of lipofuscin, which has a protective effect at moderate amounts but becomes toxic at large quantities.

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The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 5%
Australia 1 5%
Unknown 18 90%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 35%
Researcher 6 30%
Student > Bachelor 2 10%
Professor 1 5%
Other 1 5%
Other 2 10%
Unknown 1 5%
Readers by discipline Count As %
Agricultural and Biological Sciences 12 60%
Philosophy 1 5%
Environmental Science 1 5%
Biochemistry, Genetics and Molecular Biology 1 5%
Social Sciences 1 5%
Other 2 10%
Unknown 2 10%