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Is heat shock protein mediated protection against ageing and protein oxidation tissue specific?


Aging is a biological process that is not yet understood. The free radical hypothesis of aging states that is a causal relationship between the oxidation status and lifespan such that the progressive deterioration of aging organisms is a consequence of cumulative oxidation damage. In line with this, intracellular accumulation of misfolded and oxidatively damaged proteins, e.g. carbonylated proteins, has repeatedly been associated with aging and the diseases of aging. Such accumulation can be counteracted by over-expression of molecular chaperones and proteases, e.g. the Heat shock proteins (HSPs), and also of oxidant defence proteins like Superoxide dismutase (SOD).

Interestingly, elevated levels of specific HSPs as well as SOD can also prolong lifespan markedly. For example, the Tanguay lab has demonstrated that over-expression of HSP22 in mitochondria of motorneurons of the fruitfly Drosophila melanogaster increases the mean lifespan by over 30% and resistance to oxidative stress by 35%, and that the ef fect was cell type specific. In addition to carbonylation, the formation of advanced glycation end-products (AGEs) on proteins has been demonstrated to increase with age and age-related diseases and to destroy protein function and structure. AGEs are mostly formed via oxidative reactions such as carbohydrate and lipid oxidation and can therefore serve as a biomarker of those events.

In this project I will use Drosophila to address the following questions:
1) Do the levels and localization patterns of protein carbonylation and HSPs in cells and tissues differ between; a) young and old flies, b) short lived versus long lived flies.
2) Is overproduction of HSP22 and other HSPs (e.g. HSP70) reducing protein carbonylation and if so, in what tissues?
3) Is AGE-formation tissue and celltype specific in Drosophila?

I will use the bioimaging and immunocytochemistry techniques available at the Tanguay lab together with the proteomic tools I have applied during my PhD work.

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100 Göteborg

Participants (1)

Lab Cell & Developmental Genetics Pavillon Marchand