NDLI: What Goes Wrong with Lon in Ageing?

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What Goes Wrong with Lon in Ageing?

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What Goes Wrong with Lon in Ageing?

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Davies, Kelvin J. A.
Description	Country affiliation: United States Author Affiliation: Davies KJ ( University of Southern California, Andrus Gerontology Center of the Davis School of Gerontology, and Division of Molecular & Computational Biology, College of Letters, Arts & Sciences, USA.)
Abstract	We have shown previously that the product of the human lon gene, the Lon protease, selectively degrades oxidized mitochondrial proteins, thus preventing their aggregation and cross-linking. We have also shown that lon is a stress-responsive gene, whose protease product is a stress-responsive protein that is induced by multiple stressors, including heat shock, serum starvation, and oxidative stress. Lon induction, by pre-treatment with low-level stress, protects against oxidative protein damage, diminished mitochondrial function, and loss of cell proliferation, induced by toxic levels of hydrogen peroxide. Blocking Lon induction, with lon siRNA, also blocks this induced protection. All of these results were obtained in young, healthy cells. In senescent cells, and in older primary cells, however, Lon activity declines, and adaptational responses become sluggish or even ineffectual. Studies in Drosophila melanogaster flies and in mice now suggest that declining Lon activity and declining responsiveness to stress, may contribute to the ageing process, and to various age-associated diseases. We propose that Lon is a generalized stress-protective enzyme whose decline may contribute to the increased levels of protein damage and mitochondrial dysfunction observed in ageing and various age-related diseases. We further propose that impaired ability to induce lon, and other stress-responsive genes, now needs to be included in any Free Radical Theory of Ageing.
File Format	HTM / HTML
ISSN	08915849
Issue Number	Suppl 1
Journal	Free Radical Biology and Medicine
Volume Number	75
e-ISSN	18734596
Language	English
Publisher	Elsevier
Publisher Date	2014-10-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Content Type	Text
Resource Type	Article
Subject	Physiology (medical) Biochemistry

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