Calories do not explain extension of life span by dietary restriction in Drosophila

Abstract

Dietary restriction (DR) extends life span in diverse organisms, including mammals, and common mechanisms may be at work. DR is often known as calorie restriction, because it has been suggested that reduction of calories, rather than of particular nutrients in the diet, mediates extension of life span in rodents. We here demonstrate that extension of life span by DR in Drosophila is not attributable to the reduction in calorie intake. Reduction of either dietary yeast or sugar can reduce mortality and extend life span, but by an amount that is unrelated to the calorie content of the food, and with yeast having a much greater effect per calorie than does sugar. Calorie intake is therefore not the key factor in the reduction of mortality rate by DR in this species.

Figure 1. Feeding Rates of Female Drosophila on Food Media with Different Nutrient Concentrations

Feeding rates were recorded by direct observation as the proportion of time flies spent on the surface of the media with their proboscis extended and touching the food (y-axis). Replicate measurements of the proportion of females feeding versus those not feeding were recorded during a 2-h period on the days shown. No significant different was seen between flies fed different diets on days 3, 7, 11, and 24 as assessed by chi-squared tests (p > 0.01, Bonferroni correction for multiple comparisons). There was a significant difference in feeding rates on day 17 (p = 0.0068) with flies on the DR yeast/control sugar media eating less. These data show that Drosophila does not exhibit compensatory feeding behaviour for the DR regime imposed.

Figure 2. Survivorship (l_x) Analysis of Life Span of Female Drosophila on Different Food Regimes

Colour/Symbol of the curves shows yeast level while the line type represents sugar levels in the respective foods. (A) and (B) are independent repeats. In both cases, changing caloric content of the food by altering yeast levels had a much greater effect on life span than that seen when the same change in caloric content was brought about by manipulating sugar levels.

Figure 3. Plot of Median Life Span of Female Drosophila against the Estimated Caloric Content of the Food Medium

(A) and (B) represent independent repeats. Red arrows link pairs of food types where differences in caloric content are due to different yeast concentrations. Blue arrows link pairs of food types where differences in caloric content are due to different sugar concentrations. Green arrow links food types where differences in caloric content are due to both different sugar and yeast concentrations. Life span is extended to a greater extent per calorie by reducing yeast concentration from control to DR levels than by reducing sugar. This is in contrast to what would be predicted if calorie intake were the key mediator of life-span extension by DR in fruit flies.

Figure 4. Effect of Tetracycline on Life Span of Female D. melanogaster

The addition of the antibiotic tetracycline to the food media did not have a significant effect on life span at either control or DR concentration food media.

Figure 5. The Acute Effects on Age-Specific Mortality in Drosophila of Changes in Nutritional Content of the Food Midway through Life

Vertical line represents switch day. Mortality trajectories were truncated when n < 40. (A) Switching between control and DR yeast (Y) diets midway though life results in rapid changes in age-specific mortality rates within 48 h similar to those seen previously for whole food dilutions [24]. Control yeast intake caused no irreversible damage since flies switched from control yeast to DR yeast at day 25 rapidly became no more likely to die than those flies given DR yeast levels throughout adulthood. Flies with a history of DR yeast levels showed rapid increases in mortality rate when moved to control yeast levels at day 25, but mortality rates did not become as high as those of flies that had been maintained on control yeast levels permanently. (B) Changing caloric intake to the same extent via changes to sugar (S) levels rather than yeast did not cause rapid changes in mortality rate. Despite flies chronically fed control sugar and DR yeast having increased mortality rate compared to the DR control, switching from DR to control sugar late in life did not increase mortality rate.