Adult-onset, short-term dietary restriction reduces cell aging in mice

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The first study to show that short-term Dietary Restriction (DR) reduced frequencies of senescent (aged) cells in solid tissues. It is important to note that the magnitude of the reductions, amounting to between 3.3 and 6.5% depending on the tissue compartment, is very substantial given the short duration of the treatment (Male C57/BL mice were subjected to three months of DR by average 26% of food restriction starting at 14 months of age.) Frequencies of senescent cells increase with age in intestinal crypts and liver at rates below 0.5% per month, indicating that 3 months DR probably reduced levels of senescent cells beyond that at the start of the treatment. Available data indicate that senescent hepatocytes are turned over slowly in liver. Turnover rates of senescent enterocytes in intestinal crypts are unknown. DR could block the induction of senescent cells, increase the rate of their turnover, or both

Dietary restriction (DR) extends the lifespan of a wide variety of species and reduces the incidence of major age-related diseases. Cell senescence has been proposed as one causal mechanism for tissue and organism ageing. We show for the first time that adult-onset, short-term DR reduced frequencies of senescent cells in the small intestinal epithelium and liver of mice, which are tissues known to accumulate increased numbers of senescent cells with advancing age. This reduction was associated with improved telomere maintenance without increased telomerase activity. We also found a decrease in cumulative oxidative stress markers in the same compartments despite absence of significant changes in steady-state oxidative stress markers at the whole tissue level. The data suggest the possibility that reduction of cell senescence may be a primary consequence of DR which in turn may explain known effects of DR such as improved mitochondrial function and reduced production of reactive oxygen species.

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