The genetic association of FOXO3 genotypes with human longevity is well established, although the mechanism is not fully understood. We now report on the relationship of the FOXO3 longevity variant rs2802292 with telomere length, telomerase activity, FOXO3 expression, and inflammatory cytokine levels in men and women. In agreement with earlier work, the FOXO3 longevity variant conferred protection against telomere shortening of peripheral blood mononuclear cells from adults aged 55 years and older. This was accompanied by higher levels of telomerase activity in mononuclear cells for carriers of the longevity-associated FOXO3 G-allele of SNP rs2802292 (P = 0.015). FOXO3 mRNA expression increased slightly with age in both young (P = 0.02) and old (P = 0.08) G-allele carriers. Older female G-allele carriers displayed a modest decline in levels of pro-inflammatory cytokine IL-6 with age (P = 0.07). In contrast, older male G-allele carriers displayed an age-dependent increase in levels of anti-inflammatory cytokine IL-10 with age (P = 0.04). Thus, FOXO3 may act through several different pro-longevity mechanisms, which may differ by age and sex.
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http://dx.doi.org/10.1038/s41514-024-00142-8 | DOI Listing |
Chin Med
January 2025
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Road, Nanjing, 211198, China.
Background: Cell membrane chromatography (CMC) is a biochromatography with a dual function of recognition and separation, offering a distinct advantage in screening bioactive compounds from Chinese medicines (CMs). Yindan Xinnaotong soft capsule (YD), a CM formulation, has been widely utilized in the treatment of cardiovascular disease. However, a comprehensive mapping of the myocardial protective active compounds remains elusive.
View Article and Find Full Text PDFMethods Mol Biol
November 2024
ABC-RI, Algarve Biomedical Center Research Institute, Algarve Biomedical Center, Faro, Portugal.
In mammals, the FOXO protein family consists of four distinct isoforms: FOXO1, FOXO3, FOXO4, and FOXO6. These isoforms are key players in a wide spectrum of physiological and pathological processes, including context-specific tumor suppression. FOXO3, in particular, has emerged as a gene associated with extraordinary human longevity.
View Article and Find Full Text PDFMethods Mol Biol
November 2024
ABC-RI, Algarve Biomedical Center Research Institute, Algarve Biomedical Center, Faro, Portugal.
Forkhead box O (FOXO) transcription factors constitute a mammalian family of proteins, comprising FOXO1, FOXO3, FOXO4, and FOXO6. Originally recognized as downstream regulators within the insulin pathway, FOXO factors exhibit the ability to bind to diverse target gene promoters, thereby governing crucial facets of cellular homeostasis. These encompass cellular energy generation, resilience against oxidative stress, and the modulation of cell viability and proliferation.
View Article and Find Full Text PDFJ Gerontol A Biol Sci Med Sci
December 2024
Department of Research, Kuakini Honolulu Heart Program, Center of Biomedical Research Excellence (COBRE) for Clinical and Translational Research on Aging, Kuakini Medical Center, Honolulu, Hawaii.
Background: This study tested whether the carriage of the longevity-associated G-allele of FOXO3 SNP rs2802292 (TG/GG) protects against incident coronary artery disease (CAD) in men with hypertension.
Methods: Subjects were American men residing on Oahu having Japanese (n = 5415) or Okinawan (n = 897) ancestry and free of CAD at baseline (1965-1968) when aged 45-68 years.
Results: During the follow-up, there were 1 629 incident CAD cases.
Nutrients
September 2024
Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60286, Indonesia.
Background: Fasting potentially alters the aging process induced by obesity by regulating telomere integrity, which is related to longevity genes. However, the impact of periodic fasting (PF) on the expression of longevity genes, particularly Forkhead Box O Transcription Factors (FOXO3a) and the Human Telomerase Reverse Transcriptase (hTERT), is not fully understood. This study aimed to analyze the effects of PF, specifically on FOXO3a, hTERT expression, and other associated factors.
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