Biological senescence risk score. A practical tool to predict biological senescence status

Ortiz-Morales, Ana M; Alcalá‐Díaz, Juan F.; Rangel‐Zúñiga, Oriol A.; Corina, Andreea; Quintana-Navarro, Gracia M.; Cardelo, Magdalena P.; Yubero‐Serrano, Elena M.; Malagón, Marı́a M.; Delgado-Lista, Javier; Ordovás, José M.; Pérez‐Martínez, Pablo

doi:10.1111/eci.13305

Cited by 4 publications

(4 citation statements)

References 42 publications

(61 reference statements)

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“…It was documented that IGFBP-5 seems to play a critical role in the control of cellular senescence and inflammation [41]. In addition, it was proposed that adipokines (resistin and leptin) could be used as markers of biological aging [42]. These results allow us to hypothesize that senescent osteocytes and their SASPs may contribute to radiation-induced bone loss.…”

Section: Discussionmentioning

confidence: 99%

Radiation-Induced Osteocyte Senescence Alters Bone Marrow Mesenchymal Stem Cell Differentiation Potential via Paracrine Signaling

Wang

et al. 2021

IJMS

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Cellular senescence and its senescence-associated secretory phenotype (SASP) are widely regarded as promising therapeutic targets for aging-related diseases, such as osteoporosis. However, the expression pattern of cellular senescence and multiple SASP secretion remains unclear, thus leaving a large gap in the knowledge for a desirable intervention targeting cellular senescence. Therefore, there is a critical need to understand the molecular mechanism of SASP secretion in the bone microenvironment that can ameliorate aging-related degenerative pathologies including osteoporosis. In this study, osteocyte-like cells (MLO-Y4) were induced to cellular senescence by 2 Gy γ-rays; then, senescence phenotype changes and adverse effects of SASP on bone marrow mesenchymal stem cell (BMSC) differentiation potential were investigated. The results revealed that 2 Gy irradiation could hinder cell viability, shorten cell dendrites, and induce cellular senescence, as evidenced by the higher expression of senescence markers p16 and p21 and the elevated formation of senescence-associated heterochromatin foci (SAHF), which was accompanied by the enhanced secretion of SASP markers such as IL-1α, IL-6, MMP-3, IGFBP-6, resistin, and adiponectin. When 0.8 μM JAK1 inhibitors were added to block SASP secretion, the higher expression of SASP was blunted, but the inhibition in osteogenic and adipogenic differentiation potential of BMSCs co-cultured with irradiated MLO-Y4 cell conditioned medium (CM- 2 Gy) was alleviated. These results suggest that senescent osteocytes can perturb BMSCs’ differential potential via the paracrine signaling of SASP, which was also demonstrated by in vivo experiments. In conclusion, we identified the SASP factor partially responsible for the degenerative differentiation of BMSCs, which allowed us to hypothesize that senescent osteocytes and their SASPs may contribute to radiation-induced bone loss.

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Section: Discussionmentioning

confidence: 99%

Radiation-Induced Osteocyte Senescence Alters Bone Marrow Mesenchymal Stem Cell Differentiation Potential via Paracrine Signaling

Wang

et al. 2021

IJMS

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“…Glucose measurements were performed using the hexokinase method, and highly sensitive C-reactive protein levels were measured using ELISA techniques (BioCheck, Inc., Foster City, CA, USA). Reduced (GSH) and oxidized glutathione (GSSG) were determined following the methodology previously published in [23]. GSH and GSSG content were determined in the plasma samples using the BIOXYTECH ® GSH-400 Kit, catalog number 21011 (OXIS International Inc., Portland, OR, USA), and the GSH-412 Kit, catalog number 21040 (OXIS International Inc., Portland, OR, USA), respectively.…”

Section: Laboratory Measurementsmentioning

confidence: 99%

Telomere Maintenance Is Associated with Type 2 Diabetes Remission in Response to a Long-Term Dietary Intervention without Non-Weight Loss in Patients with Coronary Heart Disease: From the CORDIOPREV Randomized Controlled Trial

Ojeda-Rodriguez,

Alcala-Diaz,

Rangel-Zuñiga

et al. 2024

Antioxidants

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In order to evaluate whether telomere maintenance is associated with type 2 diabetes remission, newly diagnosed type 2 diabetes patients without glucose-lowering treatment (183 out of 1002) from the CORDIOPREV study (NCT00924937) were randomized to consume a Mediterranean or low-fat diet. Patients were classified as Responders, those who reverted from type 2 diabetes during the 5 years of dietary intervention (n = 69), and Non-Responders, who did not achieve diabetes remission by the end of the follow-up period (n = 104). We found no differences in diabetes remission between the two diets, and we determined telomere length (TL) by measuring qPCR, telomerase activity using the TRAP assay, and direct redox balance based on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) via colorimetric assay. Responders exhibited higher baseline TL in comparison with Non-Responders (p = 0.040), and a higher TL at baseline significantly predicted a higher probability of type 2 diabetes remission (OR 2.13; 95% CI, 1.03 to 4.41). After the dietary intervention, Non-Responders showed significant telomere shortening (−0.19, 95% CI −0.32 to 0.57; p = 0.005). Telomere shortening was significantly pronounced in type 2 diabetes patients with a worse profile of insulin resistance and/or beta-cell functionality: high hepatic insulin resistance fasting, a high disposition index (−0.35; 95% CI, −0.54 to −0.16; p < 0.001), and a low disposition index (−0.25; 95% CI, −0.47 to −0.01; p = 0.037). In addition, changes in TL were correlated to the GSH/GSSG ratio. Responders also showed increased telomerase activity compared with baseline (p = 0.048), from 0.16 (95% CI, 0.08 to 0.23) to 0.28 (95% CI, 0.15 to 0.40), with a more marked increase after the dietary intervention compared with Non-Responders (+0.07; 95% CI, −0.06–0.20; p = 0.049). To conclude, telomere maintenance may play a key role in the molecular mechanisms underlying type 2 diabetes remission in newly diagnosed patients. However, further larger-scale prospective studies are necessary to corroborate our findings.

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Section: Oxs-and Inflammation-related Parametersmentioning

confidence: 99%

“…As a sample of the total population of the study, oxidative-stress and inflammationrelated data from 353 participants from the CORDIOPREV Study were acquired in the set of the PI13-00185 Grant (see acknowledgments), as previously published by our group [28]. Lipid peroxidation products (LPO), total glutathione, reduced (GSH) and oxidized glutathione (GSSG) and the GSH/GSSG ratio were determined, as previously defined [28]. GSH and GSSG content were measured in the plasma samples using the BIOXYTECH ® GSH-400 Kit (OXIS International Inc., Portland, OR, USA) and the GSH-412 Kit (OXIS International Inc., Portland, OR, USA), respectively.…”

Section: Oxs-and Inflammation-related Parametersmentioning

confidence: 99%

Diet and SIRT1 Genotype Interact to Modulate Aging-Related Processes in Patients with Coronary Heart Disease: From the CORDIOPREV Study

et al. 2022

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We investigated whether long-term consumption of two healthy diets (low-fat (LF) or Mediterranean (Med)) interacts with SIRT1 genotypes to modulate aging-related processes such as leucocyte telomere length (LTL), oxidative stress (OxS) and inflammation in patients with coronary heart disease (CHD). LTL, inflammation, OxS markers (at baseline and after 4 years of follow-up) and SIRT1-Single Nucleotide Polymorphisms (SNPs) (rs7069102 and rs1885472) were determined in patients from the CORDIOPREV study. We analyzed the genotype-marker interactions and the effect of diet on these interactions. Regardless of the diet, we observed LTL maintenance in GG-carriers for the rs7069102, in contrast to carriers of the minor C allele, where it decreased after follow-up (p = 0.001). The GG-carriers showed an increase in reduced/oxidized glutathione (GSH/GSSG) ratio (p = 0.003), lower lipid peroxidation products (LPO) levels (p < 0.001) and a greater decrease in tumor necrosis factor-alpha (TNF-α) levels (p < 0.001) after follow-up. After the LF diet intervention, the GG-carriers showed stabilization in LTL which was significant compared to the C allele subjects (p = 0.037), although the protective effects found for inflammation and OxS markers remained significant after follow-up with the two diets. Patients who are homozygous for the SIRT1-SNP rs7069102 (the most common genotype) may benefit from healthy diets, as suggested by improvements in OxS and inflammation in patients with CHD, which may indicate the slowing-down of the aging process and its related diseases.

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Biological senescence risk score. A practical tool to predict biological senescence status

Cited by 4 publications

References 42 publications

Radiation-Induced Osteocyte Senescence Alters Bone Marrow Mesenchymal Stem Cell Differentiation Potential via Paracrine Signaling

Radiation-Induced Osteocyte Senescence Alters Bone Marrow Mesenchymal Stem Cell Differentiation Potential via Paracrine Signaling

Telomere Maintenance Is Associated with Type 2 Diabetes Remission in Response to a Long-Term Dietary Intervention without Non-Weight Loss in Patients with Coronary Heart Disease: From the CORDIOPREV Randomized Controlled Trial

Diet and SIRT1 Genotype Interact to Modulate Aging-Related Processes in Patients with Coronary Heart Disease: From the CORDIOPREV Study

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