Biogerontology最新文献

The chronic inflammation present in aged individuals is generally depicted as a detrimental player for longevity. Here, it is discussed several beneficial effects associated with the cytokines that are chronically elevated in inflammaging. These cytokines, such as IL-1β, type I interferons, IL-6 and TNF positively regulate macroautophagy, mitochondrial function, anti-tumor immune responses and skeletal muscle biogenesis, possibly contributing to longevity. On the other side, the detrimental and antagonistic role of these cytokines including the induction of sarcopenia, tissue damage and promotion of tumorigenesis are also discussed, underscoring the dichotomy associated with inflammaging and its players. In addition, it is discussed the role of the anti-inflammatory cytokine IL-10 and other cytokines that affect aging in a more linear way, such as IL-11, which promotes senescence, and IL-4 and IL-15, which promotes longevity. It is also discussed more specific regulators of aging that are downstream cytokines-mediated signaling.

Coronary heart disease (CHD) and cognitive impairment frequently co-occur in aging populations, yet the molecular mechanisms linking these conditions remain unclear. This study aims to elucidate the roles of key aging-related genes (ARGs), specifically FKBP5 and DDIT3, in the pathophysiology of CHD and cognitive impairment, and to evaluate the therapeutic potential of stellate ganglion block (SGB). Using single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data, we identified FKBP5 and DDIT3 as pivotal genes upregulated in both conditions. Experimental findings show that SGB effectively modulates these ARG-related pathways through autonomic regulation, specifically suppressing estrogen and NF-κB signaling pathways, thereby reducing the expression of pro-inflammatory cytokines such as SRC, MMP2, FKBP5, IRAK1, and MYD88, while upregulating the vasodilation-related gene NOS3. This modulation improved endothelial and cardiac function and enhanced cerebral blood flow (CBF), leading to cognitive improvement. Behavioral assessments, including novel object recognition (NOR) and Morris water maze (MWM) tests, demonstrated that SGB-treated rats outperformed untreated MI rats, with significant cognitive recovery over time. Further support from laser Doppler flowmetry (LDF) and electroencephalogram (EEG) analyses revealed increased left frontal blood flow and stabilized neural activity, indicating a favorable neurophysiological environment for cognitive rehabilitation. Our findings suggest that left stellate ganglion block (LSGB) provides both cardiac and cognitive benefits through targeted gene modulation, establishing its therapeutic potential for addressing the intersecting pathologies of CHD and cognitive impairment.

GdVO₄:Eu³⁺ nanoparticles (OVNPs) have previously been shown to exhibit anti-aging effects in old rats.The accelerated aging model (overnutrition in early postnatal ontogenesis (POF)) was used to confirm the effect of OVNPs as a potential geroprotector. A comparative study of the effect of OVNPs, calorierestriction (CR) and CR-mimetic-metformin was carried out using a number of criteria: survival, prooxidant-antioxidant balance in the liver and blood, physiological parameters of male Wistar rats with accelerated aging. It was found that the survival of rats with POF was lower than that of control animals.It was found that the rate of superoxide radical formation and the content of lipid hydroperoxides in the mitochondria and microsomes of the liver and blood serum of rats with POF were higher, and the activities of glutathione peroxidases and the GSH content were significantly lower than in the control animals.It was also found that POF leads to perturbation of physiological parameters (body weight, liver weight, liver mass coefficient, body temperature and blood thyroxine concentration) characterizing the quality of life. Long-term use of OVNPs, CR or metformin in rats with accelerated aging normalized the imbalance of the prooxidant-antioxidant system, improved the physiological parameters, and increased the survival of these experimental animals. Moreover, the increase in survival was most pronounced with the use of CR and OVNPs. Considering our results andthe inadmissibility of long-term use of CR, it should be concluded that GdVO₄:Eu³⁺ nanoparticles are promising for the development of agents that slow down the accelerated aging of an organism.

Endothelial cell (EC) senescence is a major contributor in atherosclerosis (AS) development. Herein, the role of forkhead box P transcription factor 1 (FOXP1) and insulin-like growth factor (IGF)-1 in regulating EC senescence during AS progression was investigated. The mRNA and protein expressions were assessed using qRT-PCR and western blot. IL-1β and IL-18 secretion levels were analyzed by ELISA. Cell viability and pyroptosis were determined by MTT assay and flow cytometry, respectively. SA β-Gal staining was used to measure cell senescence. Tube formation assay was adopted to detect the angiogenesis ability. Dual-luciferase reporter and ChIP assays were used to investigate the relationship between FOXP1 and IGF‑1. ox-LDL stimulation significantly reduced FOXP1 and IGF-1 expression levels in human aortic endothelial cells (HAECs). FOXP1 or IGF-1 overexpression both mitigated ox-LDL-induced cellular senescence and NLRP3 activation in HAECs. It was subsequently revealed that FOXB1 transcriptionally activated IGF-1 expression in HAECs by binding to IGF-1 promoter. Rescue experiments demonstrated that IGF-1 silencing abolished the inhibitory impact of FOXP1 overexpression on ox-LDL-induced cellular senescence and NLRP3 activation in HAECs. FOXP1 transcriptionally activated IGF-1 to lighten ox-LDL-induced endothelial cellular senescence by inactivating NLRP3 inflammasome.

This article examines the framing and public perception of longevity biotechnology, or geroscience, which aims to extend both healthspan and lifespan by targeting the biological processes of aging. Although often seen as moving into the mainstream, questions remain about its ability to meet these ambitious goals, given the complexities of understanding and manipulating aging biology. Drawing on an analysis of qualitative studies and surveys conducted over the past two decades, this paper explores how public attitudes toward anti-aging science are framed, suggesting that studies often emphasize life extension over healthspan gains. Findings reveal mixed reactions, with both interest in and ambivalence about the desirability of extended lifespans. In response, this paper recommends that stakeholders in longevity biotechnology engage with the public by understanding unmet health needs rather than assuming a widespread embrace of lifespan extension. The article underscores the importance of aligning public engagement strategies with realistic scientific expectations to foster credibility and trust; promises should be grounded in current scientific evidence and tempered by feasibility. Addressing societal concerns and fostering dialogue on the ethical and social implications of manipulating aging processes could lay a foundation for responsible progress in geroscience and biogerontology, supporting a more informed, inclusive conversation between science and society as these fields advance.

Age-related cognitive impairment is a prevalent issue in developed societies. Gamma oscil2lations at 40 Hz have been identified as a potential therapeutic approach for age-related cognitive decline and can be induced through various modalities, including auditory, visual, electrical, and magnetic stimulation. In this study, we investigated a novel modality of stimulation: whole-body vibration at 40 Hz. We examined the effects of 40 Hz vibration on cognitive performance and associated neuronal activity in the brains of aged male rats. Our findings revealed that only vibration at 40 Hz, rather than 20 Hz or 80 Hz, elicited cortical gamma oscillations in aged male rats. Additionally, following 8 weeks of prolonged treatment, the implementation of 40 Hz whole-body vibration significantly augmented the cognitive function of aged male rats as evidenced by behavioral assessments. Mechanistic studies demonstrated that these beneficial effects were attributed to the reduction of neuronal apoptosis in hippocampal CA1 through regulation of synaptic connections between astrocytes and neurons via 40 Hz gamma oscillations. Collectively, this suggests a promising intervention for age-related cognitive decline and identifies neuron-astrocyte synapses as potential therapeutic targets.

Ageing is an inevitable and multifaceted biological process that impacts a wide range of cellular and molecular mechanisms, leading to the development of various diseases, such as liver fibrosis. Liver fibrosis progresses to cirrhosis, which is an advanced form due to high amounts of extracellular matrix and restoration of normal liver structure with failure to repair damaged tissue and cells, marking the end of liver function and total liver failure, ultimately death. The most important factors are reactive oxygen species (ROS) and cellular senescence. Oxidative stress is defined as an impairment by ROS, which are by-products of the mitochondrial electron transport chain and other key molecular pathways that induce cell damage and can activate cellular senescence pathways. Cellular senescence is characterized by pro-inflammatory cytokines, growth factors, and proteases secreted by senescent cells, collectively known as the senescence-associated secretory phenotype (SASP). The presence of senescent cells, which disrupt tissue architecture and function and increase senescent cell production in liver tissues, contributes to fibrogenesis. Hepatic stellate cells (HSCs) are activated in response to chronic liver injury, oxidative stress, and senescence signals that drive excessive production and deposition of extracellular matrix. This review article aims to provide a comprehensive overview of the pathogenic role of ROS and cellular senescence in the aging liver and their contribution to fibrosis.

The suprachiasmatic nucleus (SCN) in the hypothalamus regulates circadian timing system (CTS) by co-ordinating peripheral tissue clocks and extra-SCN oscillators in the brain. Aging disrupts the CTS, impairing physiological functions and reducing antioxidant defences, which contribute to neurodegeneration. The brain is vulnerable to oxidative damage due to its high metabolic activity, oxygen consumption, and levels of iron and lipids. Antioxidant enzymes, such as catalase (CAT), glutathione S-transferase (GST), superoxide dismutase (SOD), and lipid peroxidation (LPO), help against oxidative damage. In this study, we examined the temporal patterns of these antioxidant stress indicators in the SCN and extra-SCN brain regions (frontal cortex, cerebellum, and hippocampus) at various time points in male Wistar rats 3, 12, and 24 months. The rhythmicity of GST and LPO levels persisted across brain regions with aging, while CAT rhythmicity was lost in the SCN and hippocampus of older rats. SOD rhythmicity persisted in cortex, cerebellum, and hippocampus but was lost in the SCN. The daily rhythm parameters of CAT were affected most significantly, followed by SOD, GST, and LPO. Our findings demonstrate that aging leads to desynchronization of oxidative stress indicators potentially contributing to neurodegeneration and circadian dysfunction with varying effects across different brain tissues.

Age-related hearing loss (ARHL) is a common disease among the elderly. Although its pathogenesis remains unclear by now, it is widely accepted that ARHL is associated with the degenerative alterations within each component of the cochlea. Extracellular matrix (ECM) plays a crucial role in cochlear structure and function, providing not only structural support but also participating in vital physiological processes including the development, differentiation, survival of auditory sensory cells, and sound perception. ECM is implicated in the pathogenesis of various neurodegenerative diseases, with certain ECM proteins or associated molecules emerging as potential therapeutic targets. However, few research were carried out on ECM in the cochlea and ECM associated molecules in ARHL. This review aims to delineate the composition of ECM in the cochlea, the changes of the main ECM structure in the cochlea such as the tectorial membrane (TM), the basilar membrane (BM) and the spiral ligament (SL) during aging, as well as the role of ECM associated molecules in ARHL. We hope that this review will foster further research into ARHL.