SenoIndex: S100A8/S100A9 as a novel aging biomarker

Zhang, Baohu; Yan, Haoteng; Liu, Xiaoqian; Sun, Liang; Ma, Shuai; Wang, Si; Qu, Jing; Liu, Guang‐Hui; Zhang, Weiqi

doi:10.1093/lifemedi/lnad022

Cited by 15 publications

(2 citation statements)

References 8 publications

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“…Therefore, downregulation of MMP12 by formula could have antiaging effects. S1007A, S100A8 and S100A9 27 were all downregulated. S100A7 is induced by telomere dysfunction 28 and S100A8 and A9 are involved in Psoriasis vulgaris 29 .…”

Section: Resultsmentioning

confidence: 96%

Senomorphic activity of a combination of niacinamide and hyaluronic acid: correlation with clinical improvement of skin aging

Bogdanowicz,

Bensadoun,

Noizet

et al. 2024

Sci Rep

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Intrinsic and extrinsic factors, including lifestyle and sun exposure, can contribute to cell senescence, which impairs skin homeostasis, that may in turn lead to skin aging. Senescent cells have a specific secretome, called the senescence-associated secretory phenotype (SASP) that includes MMPs, CXCLs and S100A8/9. Reducing the SASP with senotherapeutics is a promising strategy to reduce skin aging. Here we evaluated the effect of a formula containing niacinamide and hyaluronic acid, which are known to limit senescence and skin aging. We conducted three different studies. (1) Ex vivo explants treated with the formula had more collagen and glycosaminoglycan. (2) In a clinical trial with forty-four women, two months of treatment improved fine lines, wrinkles, luminosity, smoothness, homogeneity, and plumpness. (3) In a third study on thirty women, we treated one arm for two months and took skin biopsies to study gene expression. 101 mRNAs and 13 miRNAs were differentially expressed. We observed a likely senomorphic effect, as there was a decrease in many SASP genes including MMP12 and CXCL9 and a significant downregulation of autocrine signaling genes: S100A8 and S100A9. These pharmaco-clinical results are the first to demonstrate the senomorphic properties of an effective anti-aging formula in skin.

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Section: Resultsmentioning

confidence: 96%

Senomorphic activity of a combination of niacinamide and hyaluronic acid: correlation with clinical improvement of skin aging

Bogdanowicz,

Bensadoun,

Noizet

et al. 2024

Sci Rep

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“…ApoE isoform-dependent differences are also observed in the phagocytosis of fibrillar Aβ, which is regulated also by S100A9 [27,28]. Although it was suggested that S100A9 and ApoE may interact with each other, there is no evidence of their direct interaction available to date [29].…”

Section: Introductionmentioning

confidence: 99%

ApoE Isoforms Inhibit Amyloid Aggregation of Proinflammatory Protein S100A9

Ghosh,

Tamilselvi,

Williams

et al. 2024

IJMS

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Increasing evidence suggests that the calcium-binding and proinflammatory protein S100A9 is an important player in neuroinflammation-mediated Alzheimer’s disease (AD). The amyloid co-aggregation of S100A9 with amyloid-β (Aβ) is an important hallmark of this pathology. Apolipoprotein E (ApoE) is also known to be one of the important genetic risk factors of AD. ApoE primarily exists in three isoforms, ApoE2 (Cys112/Cys158), ApoE3 (Cys112/Arg158), and ApoE4 (Arg112/Arg158). Even though the difference lies in just two amino acid residues, ApoE isoforms produce differential effects on the neuroinflammation and activation of the microglial state in AD. Here, we aim to understand the effect of the ApoE isoforms on the amyloid aggregation of S100A9. We found that both ApoE3 and ApoE4 suppress the aggregation of S100A9 in a concentration-dependent manner, even at sub-stoichiometric ratios compared to S100A9. These interactions lead to a reduction in the quantity and length of S100A9 fibrils. The inhibitory effect is more pronounced if ApoE isoforms are added in the lipid-free state versus lipidated ApoE. We found that, upon prolonged incubation, S100A9 and ApoE form low molecular weight complexes with stochiometric ratios of 1:1 and 2:1, which remain stable under SDS-gel conditions. These complexes self-assemble also under the native conditions; however, their interactions are transient, as revealed by glutaraldehyde cross-linking experiments and molecular dynamics (MD) simulation. MD simulation demonstrated that the lipid-binding C-terminal domain of ApoE and the second EF-hand calcium-binding motif of S100A9 are involved in these interactions. We found that amyloids of S100A9 are cytotoxic to neuroblastoma cells, and the presence of either ApoE isoforms does not change the level of their cytotoxicity. A significant inhibitory effect produced by both ApoE isoforms on S100A9 amyloid aggregation can modulate the amyloid-neuroinflammatory cascade in AD.

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