NF-κB-Specific Suppression in Cardiomyocytes Unveils Aging-Associated Responses in Cardiac Tissue
<b>Background/Objectives</b>: Aging is associated with structural and functional changes in the heart, including hypertrophy, fibrosis, and impaired contractility. Cellular mechanisms such as senescence, telomere shortening, and DNA damage contribute to these processes. Nuclear factor ka...
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2025-01-01
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| author | Letícia Aparecida Lopes Morgado Larissa Maria Zacarias Rodrigues Daiane Cristina Floriano Silva Bruno Durante da Silva Maria Claudia Costa Irigoyen Ana Paula Cremasco Takano |
| author_facet | Letícia Aparecida Lopes Morgado Larissa Maria Zacarias Rodrigues Daiane Cristina Floriano Silva Bruno Durante da Silva Maria Claudia Costa Irigoyen Ana Paula Cremasco Takano |
| author_sort | Letícia Aparecida Lopes Morgado |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Aging is associated with structural and functional changes in the heart, including hypertrophy, fibrosis, and impaired contractility. Cellular mechanisms such as senescence, telomere shortening, and DNA damage contribute to these processes. Nuclear factor kappa B (NF-κB) has been implicated in mediating cellular responses in aging tissues, and increased NF-κB expression has been observed in the hearts of aging rodents. Therefore, NF-κB is suspected to play an important regulatory role in the cellular and molecular processes occurring in the heart during aging. This study investigates the in vivo role of NF-κB in aging-related cardiac alterations, focusing on senescence and associated cellular events. <b>Methods</b>: Young and old wild-type (WT) and transgenic male mice with cardiomyocyte-specific NF-κB suppression (3M) were used to assess cardiac function, morphology, senescence markers, lipofuscin deposition, DNA damage, and apoptosis. <b>Results</b>: Kaplan–Meier analysis revealed reduced survival in 3M mice compared to WT. Echocardiography showed evidence of eccentric hypertrophy, and both diastolic and systolic dysfunction in 3M mice. Both aged WT and 3M mice exhibited cardiac hypertrophy, with more pronounced hypertrophic changes in cardiomyocytes from 3M mice. Additionally, cardiac fibrosis, senescence-associated β-galactosidase activity, p21 protein expression, and DNA damage (marked by phosphorylated H2A.X) were elevated in aged WT and both young and aged 3M mice. <b>Conclusions</b>: The suppression of NF-κB in cardiomyocytes leads to pronounced cardiac remodeling, dysfunction, and cellular damage associated with the aging process. These findings suggest that NF-κB plays a critical regulatory role in cardiac aging, influencing both cellular senescence and molecular damage pathways. This has important implications for the development of therapeutic strategies aimed at mitigating age-related cardiovascular diseases. |
| format | Article |
| id | doaj-art-f9e7b9817e074121b0f83444fa9c346a |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-f9e7b9817e074121b0f83444fa9c346a2025-01-24T13:24:28ZengMDPI AGBiomedicines2227-90592025-01-0113122410.3390/biomedicines13010224NF-κB-Specific Suppression in Cardiomyocytes Unveils Aging-Associated Responses in Cardiac TissueLetícia Aparecida Lopes Morgado0Larissa Maria Zacarias Rodrigues1Daiane Cristina Floriano Silva2Bruno Durante da Silva3Maria Claudia Costa Irigoyen4Ana Paula Cremasco Takano5Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, BrazilDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, BrazilDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, BrazilUnidade de Hipertensao, Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (InCor-HCFMUSP), Sao Paulo 05403-000, BrazilUnidade de Hipertensao, Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (InCor-HCFMUSP), Sao Paulo 05403-000, BrazilDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil<b>Background/Objectives</b>: Aging is associated with structural and functional changes in the heart, including hypertrophy, fibrosis, and impaired contractility. Cellular mechanisms such as senescence, telomere shortening, and DNA damage contribute to these processes. Nuclear factor kappa B (NF-κB) has been implicated in mediating cellular responses in aging tissues, and increased NF-κB expression has been observed in the hearts of aging rodents. Therefore, NF-κB is suspected to play an important regulatory role in the cellular and molecular processes occurring in the heart during aging. This study investigates the in vivo role of NF-κB in aging-related cardiac alterations, focusing on senescence and associated cellular events. <b>Methods</b>: Young and old wild-type (WT) and transgenic male mice with cardiomyocyte-specific NF-κB suppression (3M) were used to assess cardiac function, morphology, senescence markers, lipofuscin deposition, DNA damage, and apoptosis. <b>Results</b>: Kaplan–Meier analysis revealed reduced survival in 3M mice compared to WT. Echocardiography showed evidence of eccentric hypertrophy, and both diastolic and systolic dysfunction in 3M mice. Both aged WT and 3M mice exhibited cardiac hypertrophy, with more pronounced hypertrophic changes in cardiomyocytes from 3M mice. Additionally, cardiac fibrosis, senescence-associated β-galactosidase activity, p21 protein expression, and DNA damage (marked by phosphorylated H2A.X) were elevated in aged WT and both young and aged 3M mice. <b>Conclusions</b>: The suppression of NF-κB in cardiomyocytes leads to pronounced cardiac remodeling, dysfunction, and cellular damage associated with the aging process. These findings suggest that NF-κB plays a critical regulatory role in cardiac aging, influencing both cellular senescence and molecular damage pathways. This has important implications for the development of therapeutic strategies aimed at mitigating age-related cardiovascular diseases.https://www.mdpi.com/2227-9059/13/1/224cardiac agingcardiac remodelingNF-κBsenescence |
| spellingShingle | Letícia Aparecida Lopes Morgado Larissa Maria Zacarias Rodrigues Daiane Cristina Floriano Silva Bruno Durante da Silva Maria Claudia Costa Irigoyen Ana Paula Cremasco Takano NF-κB-Specific Suppression in Cardiomyocytes Unveils Aging-Associated Responses in Cardiac Tissue Biomedicines cardiac aging cardiac remodeling NF-κB senescence |
| title | NF-κB-Specific Suppression in Cardiomyocytes Unveils Aging-Associated Responses in Cardiac Tissue |
| title_full | NF-κB-Specific Suppression in Cardiomyocytes Unveils Aging-Associated Responses in Cardiac Tissue |
| title_fullStr | NF-κB-Specific Suppression in Cardiomyocytes Unveils Aging-Associated Responses in Cardiac Tissue |
| title_full_unstemmed | NF-κB-Specific Suppression in Cardiomyocytes Unveils Aging-Associated Responses in Cardiac Tissue |
| title_short | NF-κB-Specific Suppression in Cardiomyocytes Unveils Aging-Associated Responses in Cardiac Tissue |
| title_sort | nf κb specific suppression in cardiomyocytes unveils aging associated responses in cardiac tissue |
| topic | cardiac aging cardiac remodeling NF-κB senescence |
| url | https://www.mdpi.com/2227-9059/13/1/224 |
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