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We have previously shown that autophagy is required for chronological longevity in the budding yeast Saccharomyces cerevisiae. Here we examine the requirements for autophagy during extension of chronological life span (CLS) by calorie restriction (CR). We find that autophagy is upregulated by two CR interventions that extend CLS: water wash CR and low glucose CR. Autophagy is required for full extension of CLS during water wash CR under all growth conditions tested. In contrast, autophagy was not uniformly required for full extension of CLS during low glucose CR, depending on the atg allele and strain genetic background. Leucine status influenced CLS during CR. Eliminating the leucine requirement in yeast strains or adding supplemental leucine to growth media extended CLS during CR. In addition, we observed that both water wash and low glucose CR promote mitochondrial respiration proficiency during aging of autophagy-deficient yeast. In general, the extension of CLS by water wash or low glucose CR was inversely related to respiration deficiency in autophagy-deficient cells. Also, autophagy is required for full extension of CLS under non-CR conditions in buffered media, suggesting that extension of CLS during CR is not solely due to reduced medium acidity. Thus, our findings show that autophagy is: (1) induced by CR, (2) required for full extension of CLS by CR in most cases (depending on atg allele, strain, and leucine availability) and, (3) promotes mitochondrial respiration proficiency during aging under CR conditions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The receptor for advanced glycation end products (RAGE) is a multiligand receptor expressed in a number of cell types, including gingival epithelia. RAGE mediates inflammation and induces cellular oxidative stress. Upregulation of RAGE is associated with various diseases, such as periodontal and cardiovascular diseases. This study examines the hypothesis that the gingiva of rats fed a calorie-restriction (CR) diet expresses lower levels of RAGE than the gingiva of rats fed an ad libitum (AL) diet., Methods: Male F344BN rats (n = 16) from the National Institute on Aging (NIA) were fed a CR (n = 8) or AL (n = 8) diet according to NIA recommendations. Rats were sacrificed by guillotine at 8 (n = 5), 18 (n = 3), 29 (n = 4), and 38 (n = 4) months of age. The gingiva from around the molars was dissected and submitted for histologic and molecular analyses., Results: Immunohistochemistry revealed that RAGE was expressed in the plasma membrane and cytoplasm of gingival epithelial cells and endothelial cells from both groups. RAGE mRNA levels were quantified relative to levels of GAPDH mRNA by real-time reverse-transcriptase polymerase chain reaction. The mean relative RAGE mRNA level in the CR group (7.26 ± 0.54) was lower than in the AL group (10 ± 1.4) (P <0.05). There were no detectable differences in RAGE expression according to animal age., Conclusion: Gingival RAGE expression in rats is reduced by calorie restriction.