Опубликована: Янв. 1, 2024
Язык: Английский
Aging Cell, Год журнала: 2023, Номер 23(2)
Опубликована: Ноя. 14, 2023
Abstract Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR healthy young‐to‐middle‐aged individuals would reduce circulating biomarkers of cellular senescence, fundamental mechanism aging and aging‐related conditions. Using plasma specimens from Comprehensive Assessment Long‐term Effects Reducing Intake Energy (CALERIE™) phase 2 study, found significantly reduced concentrations several senescence at 12 24 months compared to an ad libitum diet. machine learning, changes biomarker emerged as important predictors change HOMA‐IR insulin sensitivity index months, resting metabolic rate residual months. Finally, using adipose tissue RNA‐sequencing data subset participants, observed significant reduction senescence‐focused gene set response both baseline. Our results understanding effects humans further support link between health.
Язык: Английский
Процитировано
28
Nutrients, Год журнала: 2024, Номер 16(17), С. 2878 - 2878
Опубликована: Авг. 28, 2024
As the population ages, promoting healthy aging through targeted interventions becomes increasingly crucial. Growing evidence suggests that dietary can significantly impact this process by modulating fundamental molecular pathways. This review focuses on potential of strategies in and mechanisms which specific nutrients patterns influence key pathways involved cellular repair, inflammation, metabolic regulation. Caloric restriction, intermittent fasting, Mediterranean diet, as well ketogenic diet showed promising effects aging, possibly mTORC1 AMPK, an insulin signaling pathway. By understanding intricate interplay between pathways, we develop personalized not only prevent age-related diseases, but also promote overall health well-being throughout process.
Язык: Английский
Процитировано
8
Aging Cell, Год журнала: 2024, Номер 23(6)
Опубликована: Март 5, 2024
The identification of protein targets that exhibit anti-aging clinical potential could inform interventions to lengthen the human health span. Most previous proteomics research has been focused on chronological age instead longevity. We leveraged two large population-based prospective cohorts with long follow-ups evaluate proteomic signature longevity defined by survival 90 years age. Plasma was measured using a SOMAscan assay in 3067 participants from Cardiovascular Health Study (discovery cohort) and 4690 Age Gene/Environment Susceptibility-Reykjavik (replication cohort). Logistic regression identified 211 significant proteins CHS cohort Bonferroni-adjusted threshold, which 168 were available replication 105 replicated (corrected p value <0.05). most GDF-15 N-terminal pro-BNP both cohorts. A parsimonious protein-based prediction model built 33 selected LASSO 10-fold cross-validation validated 27 validation cohort. This outperformed basic traditional factors (demographics, height, weight, smoking) improving AUC 0.658 0.748 discovery 0.755 0.802 also found associations 169 out partially mediated physical and/or cognitive function. These findings contribute biomarkers pathways aging therapeutic delay age-related diseases.
Язык: Английский
Процитировано
7
Cell Metabolism, Год журнала: 2024, Номер 36(9), С. 1914 - 1944
Опубликована: Авг. 23, 2024
Язык: Английский
Процитировано
5
Transplantation, Год журнала: 2024, Номер 108(12), С. 2434 - 2445
Опубликована: Июнь 24, 2024
Chronic systemic inflammation is associated with mortality in patients chronic kidney disease, cardiovascular and diabetes. The goal of this study was to examine the relationship between pretransplant inflammatory biomarkers (growth differentiation factor-15 [GDF-15], interleukin-6 [IL-6], soluble tumor necrosis factor receptor-1, monokine induced by gamma interferon/chemokine [C-X-C motif] ligand 9 [MIG/CXCL9], monocyte chemoattractant protein-1, FAS, factor-α, interleukin-15, interleukin-1β) death function (DWF) after transplantation (KT).
Язык: Английский
Процитировано
4
Aging Cell, Год журнала: 2024, Номер 23(11)
Опубликована: Авг. 14, 2024
Abstract White adipose tissue (WAT) is a robust energy storage and endocrine organ critical for maintaining metabolic health as we age. Our aim was to identify cell‐specific transcriptional aberrations that occur in WAT with aging. We leveraged full‐length snRNA‐Seq histology characterize the cellular landscape of human abdominal subcutaneous prospective cohort 10 younger (≤30 years) older individuals (≥65 balanced sex body mass index (BMI). The group had greater cholesterol, very‐low‐density lipoprotein, triglycerides, thyroid stimulating hormone, aspartate transaminase compared ( p < 0.05). highlight aging associated adipocyte hypertrophy, increased proportions lipid‐associated macrophages mast cells, an upregulation immune responses linked fibrosis pre‐adipocyte, adipocyte, vascular populations, CXCL14 biomarker these processes. show has elevated levels senescence marker p16 adipocytes subpopulation driving this profile. confirm phenotypical changes without overt have comparable insulin sensitivity individuals.
Язык: Английский
Процитировано
4
Mechanisms of Ageing and Development, Год журнала: 2024, Номер 222, С. 111995 - 111995
Опубликована: Окт. 9, 2024
Fisetin, a flavonoid naturally occurring in plants, fruits, and vegetables, has recently gained attention for its potential role as senotherapeutic agent the treatment of age-related chronic diseases. Senotherapeutics target senescent cells, which accumulate with age disease, both circulating immune cell populations solid organs tissues. Senescent cells contribute to development many diseases, primarily by eliciting systemic inflammation through their senescence-associated secretory phenotype. Here, we explore whether fisetin can eliminate thereby alleviate examining current evidence from vitro studies animal models that investigate fisetin's impact on well phase I/II trials various patient populations. We discuss application humans, including challenges future directions. Our review available data suggests targeting offers promising strategy managing multiple potentially transforming healthcare older multimorbid patients. However, further are needed establish safety, pharmacokinetics, efficacy senotherapeutic, identify relevant reliable outcome measures human trials, optimize dosing, better understand possible limitations agent.
Язык: Английский
Процитировано
4
European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177290 - 177290
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102690 - 102690
Опубликована: Фев. 1, 2025
Aging strongly affects the peripheral nervous system (PNS), triggering alterations that vary depending on innervated tissue. The most frequent alteration in nerve aging is reduced fiber and glial density which can lead to abnormal functionality. Interestingly, activation of a destructive phenotype takes place macrophages across PNS while number neuronal bodies unique feature some enteric ganglia. Single cell/nucleus RNA-sequencing has unveiled striking complexity cell populations nerves, these refined type annotations could facilitate better understanding aging. While effects senescence individual types requires further characterization, use senolytics appears improve general function models Here, we review current age-related changes intracardiac, musculoskeletal, sub-sections PNS, highlighting their commonalities differences.
Язык: Английский
Процитировано
0
Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 244 - 244
Опубликована: Фев. 12, 2025
Background: Cellular senescence is a state of irreversible cell cycle arrest that serves as critical regulator tissue homeostasis, aging, and disease. While transient contributes to development, wound healing, tumor suppression, chronic drives inflammation, dysfunction, age-related pathologies, including cataracts. Lens epithelial cells (LECs), essential for maintaining lens transparency, are particularly vulnerable oxidative stress-induced senescence, which accelerates aging cataract formation. This review examines the dual role in LEC function its implications cataractogenesis, alongside emerging senotherapeutic interventions. Methods: synthesizes findings on molecular mechanisms focusing stress, mitochondrial senescence-associated secretory phenotype (SASP). It explores evidence linking formation, highlighting key studies stress responses, DNA damage, antioxidant defense. Recent advances senotherapeutics, senolytics senomorphics, analyzed their potential mitigate delay progression. Conclusions: driven by impaired redox homeostasis. These factors activate path-ways, p53/p21 p16/Rb, resulting SASP-mediated inflammation. The accumulation senescent LECs reduces regenerative capacity, disrupts cataractogenesis. Emerging such dasatinib, quercetin, metformin, show promise reducing burden modulating SASP preserve transparency.
Язык: Английский
Процитировано
0