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. 2022 Aug 16;13:4827. doi: 10.1038/s41467-022-32552-1

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© The Author(s) 2022

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Human samples from Cohort A (bone and bone marrow biopsies) and cohort B (highly enriched osteocyte fractions) were used for transcriptome-wide RNA-seq analyses; b Making use of TRRUST analyses³⁰, we found several inflammation- and stress-associated genes, including SIRT1 and NFKB1, to be upregulated in the elderly women; p values were adjusted according to Benjamini–Hochberg. c In both gene sets, CDKN1A/P21^Cip1 and several SASP markers such as CCL2 and IL6 showed consistent upregulation with aging, while CDKN2A/p16^Ink4a (due to comparatively low expression) did not change significantly. Two-sided unpaired t-tests except for CCL2, where a Kolmogorov–Smirnov test was used (cohort A: CDKN2A: p = 0.0834; CDKN1A: p < 0.0001; CCL2: p = 0.0034; IL6: p = 0.6391; cohort B: CDKN2A: p = 0.1658, CDKN1A: p < 0.0001; CCL2: p < 0.0001, IL6: p = 0.0017). d The commonly used senescence/SASP gene set (R-HSA-2559582) failed to predict the aging process in either human cohort. Nominal p value, calculated as two-sided t-test, no adjustment since only one gene set was tested; e The SenMayo gene set includes growth factors, transmembrane receptors, and cytokines/chemokines that are highly influenced by other members of the gene set. The circle size depicts groupwise interactions, arrows point the direction of these interactions. f SenMayo encodes a dense network of nine different protein classes within a strong interaction network. The size of each circle represents the connectivity with other members of the gene set, grey lines represent interactions⁹²; g Genes included in the SenMayo gene set were significantly enriched with aging in both human cohorts. Nominal p value, calculated as two-sided t-test, no adjustment since only one gene set was tested Cohort A: n = 38 (19 young, 19 old, all ♀), Cohort B: n = 30 (15 young, 15 old, all ♀). **p < 0.01, ****p < 0.0001. Fig. 1a was designed using Biorender.com. Depicted are mean ± SEM. Source data are provided as a Source Data file.