Abstract
Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O2) and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses.
Highlights
Dietary restriction (DR) increases the life span in a variety of organisms such as yeasts, nematodes, fruit flies and mammals [1,2,3]
We used male Drosophila for three reasons (i) their tissues are composed of postmitotic cells as are mammalian hearts and brains, (ii) their survival is independent of energy investment into egg production and (iii) their feeding behaviour seems to be independent of the quality of the food [13]
Chronic hypoxia decreased the life span of male Drosophila and this effect can be partially reversed by restriction of dietary amino acids
Summary
Dietary restriction (DR) increases the life span in a variety of organisms such as yeasts, nematodes, fruit flies and mammals [1,2,3] In humans, it reduces the incidence of age related chronic diseases such as diabetes, cancer and cardiovascular diseases [4]. Candidate genes that contribute to the longevity of model organisms have been identified using genetic approaches [5,6,7,8,9,10,11] Their products are involved in insulin signalling, nutrient sensing and chromosome remodelling. For example, is a major cause of cardiac and neuronal cell death in myocardial infarction and stroke It imposes conditions which are unique and probably not found in other pathological situations such as cancers or neurodegenerative diseases. Identifying the mechanisms which contribute to hypoxic cell death is a major objective to develop new strategies that would slow down ageing of human brains and hearts
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