Sneha Singhal, Jaypee Institute of information technology
For examining the activity of aging control genes, scientists fed Drosophila (fruit fly) with antibiotics. Activities of most of the aging control genes get changed, and surprisingly, these antibiotics extended the lives of the flies. Drosophila’s life increased by six days after being fed antibiotics. 70% of the genes in Drosophila reflect how the body reacts to bacteria. The rest are associated with aging (30%). As fruit flies live for 12-14 days or two weeks, it’s like gaining about 20 years of life for a human being. Yet results have suggested that rather than the aging process, the activity of these genes is more a function of the presence of bacteria as most of the genes are classical hallmarks of aging.
It was not clear what effect the antibiotics had on these genes (that control stress and immunity) when researchers starved some flies or infected others with harmful bacteria. The antibiotics helped flies to survive starvation or infection longer than normal at some ages. At other ages, the drugs either reduced the chances of survival or did not affect. The same trend was observed in further experiments on gene activity. The experiments were performed in a completely sterile environment without the use of antibiotics. The data from the original study that had raised flies on antibiotics were also analyzed. In antibiotic-fed flies, the rate of gene activity change decreased with age at a slower rate than in unfed flies. This explains why antibiotic-fed flies lived longer than unfed flies.
Moreover, an experiment with flies has shown that these genes contribute to aging. Antibiotics treated flies, and thus an enhanced tendency that with age, awake flies’ behavior decreases.
Those Caenorhabditis Elegans that are grown without a bacterial microbiome (axenic) live twice as long as those grown normally (with a bacterial microbiome). Growth conditions influence the lifespan of Drosophila, so axenic growth increases lifespan. The bacteria themselves act as a food source.
With the microbiome, there is compensation for a diet with low protein content. Conventionally median raised flies were survived for 57.5 ± 0.5 days, whereas axenic flies survived longer with a median survival of 63.9 ± 0.9 days. On plating fly extract on multiple bacterial growth media and by PCR for 16S rDNA using universal bacterial probe sets, we can verify the absence of bacterial contamination of the axenic cultures. RNA was isolated from heads of conventionally raised or axenic male flies at various ages (3, 10, 30, and 45 days) to quantify the genome-wide RNA expression profile using microarrays. Flies younger than ten days are physiologically immature, have a distinct and rapidly changing gene expression profile, so we performed the age calculation only on 10-to 45-day-old axenic flies. Interpretation of the gene expression data, beyond 45 days large numbers of flies begin to die. We limited our analysis to one sex (male) for maintaining the experimental variance.
The microbiome is responsible for 70% of the changes to gene expression that occur during aging. Germ-free flies never display some of the typical signs of aging. Almost all metabolic changes, immunity, and stress responses are dependent on microbiomes. Age-related features independent of the microbiome can serve as biomarkers.
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References:
- Shukla, A. K., Johnson, K., & Giniger, E. (2021). Common features of aging fail to occur in Drosophila raised without a bacterial microbiome. IScience, 24(7), 102703. https://doi.org/10.1016/j.isci.2021.102703
- Guo, Y., Luo, J., Wang, J., Wang, Y., & Wu, R. (2011). How to compute which genes control drug resistance dynamics. Drug Discovery Today, 16(7–8), 339–344. https://doi.org/10.1016/j.drudis.2011.02.004
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