Dietary restriction (DR) is a robust environmental method to slow aging and age-related diseases in diverse organisms.

Age-related disruption of gut integrity has been observed in both mammals and fruit flies and is a determinant of lifespan. In Drosophila, DR is able to slow the age-related decline in gut integrity.

Although commensal dysbiosis has been proposed as a leading cause of gut barrier dysfunction, antibiotic treatment does not prevent the age-related increase in gut permeability.

We identify that an intrinsic mechanism regulates gut barrier function through regulation of enterocyte apoptosis by ‘cell competition’.

We show DR up-regulates dMyc expression in the gut which enhances enterocyte cellular fitness, prevents the age-related decline in gut integrity, and contributes to DR-induced lifespan extension.

Conversely, on a rich diet, inhibition of dMyc in the enterocytes leads to cell death that enhances gut permeability and leads to systemic inflammation and shortened lifespan.

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