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. 2023 Dec 8;14:8142. doi: 10.1038/s41467-023-43672-7

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — a Schematic overview of isofalcarintriol (1a) supplementation study with aged C57BL/6NRj mice on chow diet. b Glucose tolerance test 20-month-old male mice (DMSO: n = 10; IFT: n = 11 mice; 15 min: p = 0.03) and (c) fasted blood glucose levels at 29 months of age (n = 21 mice per treatment). d Glucose tolerance test in 20-month-old female mice (n = 12 per treatment) and (e) fasted blood glucose levels at 29 months of age (n = 18 mice per treatment). Total frailty index (FI) score of (f) male (22 months: p = 0.0078; 25 months: p = 0.0005; 28 months: p = 0.0254, 31 months: p = 0.0007) and (h) female mice (p = 0.03) (n = as indicated below bars). Calculated phenotypical age based on FI scores, (g) of male mice (28 months: p = 0.0169; 31 months: p = 0.0246) and (i) of female mice (n = as indicated in panels). Sex-independent frailty parameters, shown as males and females combined, including (j) endurance capacity (p = 0.03) (n = 37 mice per treatment), (k) total frailty index score at individual endpoints (p = 0.01), as well as (l) grimace and (m) breathing scores (28 months: p = 0.0378). Sex-dependent health parameters in either male or female mice, including (n) grip strength of male mice (month 28) (DMSO: n = 16; IFT: n = 15 mice) (p = 0.0036), o heart rate variability (HRV) (p = 0.0014) and p coefficient of variation (CV) (p = 0.002) as measured via electrocardiogram (ECG) in female mice (month 27) (DMSO: n = 18; IFT: n = 17 mice), q White blood cell count (WBC) (p = 0.04), and number of lymphocytes (LYM) (p = 0.048) (DMSO: n = 11; IFT: n = 8) as well as concentration of anti-inflammatory cytokines (r) IL-4 (p = 0.0064) and (s) IL-10 (p = 0.0070) in female plasma (month 29) (n = 7 mice per treatment). Data in (b)–(e), (j), and (n)–(r) are represented as average + SD or ± SD. Box plots indicate median (middle line), 25^th, 75^th percentile (box) and min, max values (whiskers). Data in (l) and (m) show the average ± SEM. Statistics: two-sided unpaired student’s t-test; two-way repeated measures ANOVA; mixed effects analysis; Mann–Whitney test. Source data are provided as a Source Data file.