dNAGLU Extends Life Span and Promotes Fitness and Stress Resistance in Drosophila
To identify new factors that promote longevity and healthy aging, we studied , an ortholog of the human gene, a lysosomal enzyme overexpressed in centenarians. We found that the overexpression of ( ) ubiquitously, or tissue specifically, in the nervous system or fat body could extend fly life span....
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Published in | International journal of molecular sciences Vol. 23; no. 22; p. 14433 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
20.11.2022
MDPI |
Subjects | |
Online Access | Get full text |
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Summary: | To identify new factors that promote longevity and healthy aging, we studied
, an ortholog of the human
gene, a lysosomal enzyme overexpressed in centenarians. We found that the overexpression of
(
) ubiquitously, or tissue specifically, in the nervous system or fat body could extend fly life span. It also extended the life span of flies overexpressing human Aβ42, in a
Alzheimer's disease (AD) model. To investigate whether
could influence health span, we analyzed the effect of its overexpression on AD flies and found that it improved the climbing ability and stress resistance, including desiccation and hunger, suggesting that
improved fly health span. We found that the deposition of Aβ42 in the mushroom body, which is the fly central nervous system, was reduced, and the lysosomal activity in the intestine was increased in
over-expressing flies. When
was overexpressed in human U251-APP cells, which expresses a mutant form of the Aβ-precursor protein (APP), APP-p.M671L, these cells exhibited stronger lysosomal activity and and enhanced expression of lysosomal pathway genes. The concentration of Aβ42 in the cell supernatant was reduced, and the growth arrest caused by APP expression was reversed, suggesting that
could play a wider role beyond its catalytic activity to enhance lysosomal activity. These results also suggest that
overexpression could be explored to promote healthy aging and to prevent the onset of neurodegenerative diseases, including AD. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
ISSN: | 1422-0067 1661-6596 1422-0067 |
DOI: | 10.3390/ijms232214433 |