Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone?
Cellular senescence is a state of permanent cell cycle arrest accompanied by metabolic activity and characteristic phenotypic changes. This process is crucial for developing age-related diseases, where excessive calorie intake accelerates metabolic dysfunction and aging. Overnutrition disturbs key m...
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| Format: | Article |
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MDPI AG
2025-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/1/99 |
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| author | Lara Russo Serena Babboni Maria Grazia Andreassi Jalil Daher Paola Canale Serena Del Turco Giuseppina Basta |
| author_facet | Lara Russo Serena Babboni Maria Grazia Andreassi Jalil Daher Paola Canale Serena Del Turco Giuseppina Basta |
| author_sort | Lara Russo |
| collection | DOAJ |
| description | Cellular senescence is a state of permanent cell cycle arrest accompanied by metabolic activity and characteristic phenotypic changes. This process is crucial for developing age-related diseases, where excessive calorie intake accelerates metabolic dysfunction and aging. Overnutrition disturbs key metabolic pathways, including insulin/insulin-like growth factor signaling (IIS), the mammalian target of rapamycin (mTOR), and AMP-activated protein kinase. The dysregulation of these pathways contributes to insulin resistance, impaired autophagy, exacerbated oxidative stress, and mitochondrial dysfunction, further enhancing cellular senescence and systemic metabolic derangements. On the other hand, dysfunctional endothelial cells and adipocytes contribute to systemic inflammation, reduced nitric oxide production, and altered lipid metabolism. Numerous factors, including extracellular vesicles, mediate pathological communication between the vascular system and adipose tissue, amplifying metabolic imbalances. Meanwhile, caloric restriction (CR) emerges as a potent intervention to counteract overnutrition effects, improve mitochondrial function, reduce oxidative stress, and restore metabolic balance. CR modulates pathways such as IIS, mTOR, and sirtuins, enhancing glucose and lipid metabolism, reducing inflammation, and promoting autophagy. CR can extend the health span and mitigate age-related diseases by delaying cellular senescence and improving healthy endothelial–adipocyte interactions. This review highlights the crosstalk between endothelial cells and adipocytes, emphasizing CR potential in counteracting overnutrition-induced senescence and restoring vascular homeostasis. |
| format | Article |
| id | doaj-art-3f197f7340be43a7b925bbb2145958ab |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-3f197f7340be43a7b925bbb2145958ab2025-01-24T13:19:29ZengMDPI AGAntioxidants2076-39212025-01-011419910.3390/antiox14010099Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone?Lara Russo0Serena Babboni1Maria Grazia Andreassi2Jalil Daher3Paola Canale4Serena Del Turco5Giuseppina Basta6Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, ItalyInstitute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, ItalyInstitute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, ItalyDepartment of Biology, Faculty of Arts and Sciences, University of Balamand, El-Koura 100, LebanonInstitute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, ItalyInstitute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, ItalyInstitute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, ItalyCellular senescence is a state of permanent cell cycle arrest accompanied by metabolic activity and characteristic phenotypic changes. This process is crucial for developing age-related diseases, where excessive calorie intake accelerates metabolic dysfunction and aging. Overnutrition disturbs key metabolic pathways, including insulin/insulin-like growth factor signaling (IIS), the mammalian target of rapamycin (mTOR), and AMP-activated protein kinase. The dysregulation of these pathways contributes to insulin resistance, impaired autophagy, exacerbated oxidative stress, and mitochondrial dysfunction, further enhancing cellular senescence and systemic metabolic derangements. On the other hand, dysfunctional endothelial cells and adipocytes contribute to systemic inflammation, reduced nitric oxide production, and altered lipid metabolism. Numerous factors, including extracellular vesicles, mediate pathological communication between the vascular system and adipose tissue, amplifying metabolic imbalances. Meanwhile, caloric restriction (CR) emerges as a potent intervention to counteract overnutrition effects, improve mitochondrial function, reduce oxidative stress, and restore metabolic balance. CR modulates pathways such as IIS, mTOR, and sirtuins, enhancing glucose and lipid metabolism, reducing inflammation, and promoting autophagy. CR can extend the health span and mitigate age-related diseases by delaying cellular senescence and improving healthy endothelial–adipocyte interactions. This review highlights the crosstalk between endothelial cells and adipocytes, emphasizing CR potential in counteracting overnutrition-induced senescence and restoring vascular homeostasis.https://www.mdpi.com/2076-3921/14/1/99senescenceendothelial dysfunctionadipocytescaloric restrictionoxidative stress |
| spellingShingle | Lara Russo Serena Babboni Maria Grazia Andreassi Jalil Daher Paola Canale Serena Del Turco Giuseppina Basta Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone? Antioxidants senescence endothelial dysfunction adipocytes caloric restriction oxidative stress |
| title | Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone? |
| title_full | Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone? |
| title_fullStr | Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone? |
| title_full_unstemmed | Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone? |
| title_short | Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone? |
| title_sort | treating metabolic dysregulation and senescence by caloric restriction killing two birds with one stone |
| topic | senescence endothelial dysfunction adipocytes caloric restriction oxidative stress |
| url | https://www.mdpi.com/2076-3921/14/1/99 |
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