Michael R Posted March 29, 2018 Report Share Posted March 29, 2018 All: Aging Cell. 2018 Mar 25:e12746. doi: 10.1111/acel.12746. [Epub ahead of print]The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon.Fontana L1,2, Mitchell SE3, Wang B4, Tosti V1, van Vliet T4, Veronese N1, Bertozzi B1, Early DS1, Maissan P4, Speakman JR3,5, Demaria M... Here, we show that a number of classical transcriptomic markers of senescent cells are reduced in adult but relatively young mice under CR. [FULL: "mice were aged 20 weeks when they entered four levels of CR for 12 weeks: 10%, 20%, 30%, and 40% restriction from baseline food intake"]. Moreover, we demonstrate that such senescence markers are not induced in the colon of middle-age human volunteers under CR in comparison with age-matched volunteers consuming normal Western diets.[specifically: "we recruited and studied 12 middle‐aged (61.7 ± 8.4 years), weight‐stable very lean (BMI = 19.1 ± 1.3 kg/m2) members of the Calorie Restriction Society who have been practicing ~30% CR with adequate nutrition (at least 100% of RDI for each nutrient) for an average of 10.1 years ... and a control group of 12 nonobese (BMI = 27.4 ± 2.5 kg/m2) age‐matched sedentary controls eating a typical Western diet (WD‐o; Figure 2a) ... [whom] we compared ... with younger (24.3 ± 2.0 years, range 21–27 years) nonobese (BMI = 25.7 ± 0.9 kg/m2) humans (WD‐y). All the genes measured were expressed at higher level in WD‐o than in WD‐y volunteers.""Levels of p16 were significantly lower in the CR compared to WD‐o volunteers (Figure 2b). Levels of p21 followed the trend observed in p16, but did not reach statistical significance (Figure 2c). In accordance with a previous study, we observed significantly lower level of the pro‐inflammatory cytokine IL‐6 in the CR colon mucosa (Figure 2d; You, Sonntag, Leng & Carter, 2007). The other SASP factors analyzed Cxcl1, Il8, Il1a, and Mmp9 followed similar trends, but only the latter two reached statistical significance (Figure 2e)." [i can't post the Figure here due to Forum software rules, but see https://wol-prod-cdn.literatumonline.com/cms/attachment/ea5d511e-f43a-42f1-9361-9284e344a7fa/acel12746-fig-0002-m.jpg[MR: the gist of it, tho' the numbers are not all statistically significant, is pretty clearly that 61-y.o. CR practitioners' senescent cell burden is clearly much closer to that of 24-y.o. AL than to age-matched AL controls, with p16, IL-6, and IL-1α (which last enforces the SASP through a positive feedback loop) being the most dramatic.]PMID: 29575469 https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12746 Diet quality may play into this, and the fact that the 27.4 ± 2.5 kg/m2 average BMI in the controls includes some significantly overweight people. And it's n-12, and only in the colon, where narrow diet effects might be most strongly observed (note that dietary influences on colorectal and GI cancers are more consistent than other tissues). But it seems pretty good evidence that human CR suppresses SC accumulation rather strongly, consistent with CR's tranlatability. Quote Link to comment Share on other sites More sharing options...
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