Biogerontology最新文献

Phytochemicals represent emerging anti-aging therapeutic candidates, with Marchantia polymorpha L. (liverwort) gaining significant attention due to its broad-spectrum pharmacological properties. This plant exhibits remarkable wound-healing and regenerative capabilities, making it a promising candidate for the development of modern anti-aging drugs. In the presented study, 12-ethoxy-Marchantin A (EMA), a new macrocyclic bis-bibenzyl compound, was isolated and identified from M. polymorpha. Using a Lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 macrophage model, a Caenorhabditis elegans (C. elegans) aging model, and network pharmacology analysis, we systematically investigated the pharmacological mechanisms underlying its anti-aging effects. Our results demonstrated that EMA significantly reduced inflammatory cytokines and nitric oxide (NO) in LPS-stimulated RAW264.7 cells via the nuclear factor erythroid 2-related factor 2 (Nrf2) / heme oxygenase (HO-1) pathway. Mechanistically, EMA triggered a reactive oxygen species (ROS)-mediated mitogen-activated protein kinase (MAPK)-dependent Nrf2 antioxidant signaling cascade. EMA significantly extended the lifespan and enhanced fecundity in the N2 strain of C. elegans, while reducing lipofuscin deposition and ROS levels. Additionally, EMA enhanced oxidative and heat stress resistance in the N2 strain of C. elegans. Network pharmacology revealed that its anti-aging effects may be mediated by MAPKs/Nrf2/HO-1 pathway regulation. Collectively, these findings highlight EMA as a potent anti-aging with therapeutic potential for aging-related conditions.

Chrysin (5,7-dihydroxyflavone), a natural flavonoid present in honey, propolis, and various medicinal plants, has shown promise as a calorie restriction mimetic (CRM) through its glycolysis-inhibiting action. This inhibition promotes a metabolic shift toward oxidative phosphorylation and fatty acid oxidation, potentially activating beneficial pathways like AMPK and SIRT1. The mechanism likely involves the downregulation of Hexokinase-2, leading to suppressed glycolysis and promotion of apoptosis. In this study, we assessed aging biomarkers in erythrocytes, plasma, and serum after administering chrysin (100 mg/kg, orally) and D-galactose (300 mg/kg, subcutaneously) for four weeks to Wistar rats. In the D-galactose-induced aging rat model, the markers of oxidative damage, such as protein carbonyls, malondialdehyde, and advanced oxidation protein products, were found to be elevated. However, chrysin treatment significantly upregulated antioxidant defenses, including catalase, superoxide dismutase, ferric-reducing antioxidant power (FRAP), and glutathione (GSH). Administration of chrysin to aged rats led to a decline in both inflammatory biomarkers and insulin concentrations. These findings suggest that chrysin can alleviate oxidative stress, reduce lipid peroxidation, and influence inflammation and metabolism, highlighting its potential as an anti-aging therapeutic agent. This study underscores the potential of chrysin as a natural calorie restriction mimetic, mainly by maintaining redox balance by impacting longevity pathways and metabolic health.

Sarcopenia, the progressive loss of skeletal muscle mass and function with aging, is a growing public health concern. Conventional treatments such as exercise, pharmacological agents, and nutritional support offer limited efficacy, especially in older populations with reduced mobility or comorbidities. This study aimed to evaluate low-intensity pulsed ultrasound (LIPUS) as a novel, non-invasive therapeutic approach for age-related muscle atrophy. LIPUS was applied to the right hindlimbs of young (12-week), middle-aged (60-week), and aged (95-week) mice for 8 weeks. Muscle weights and mRNA expression levels were analyzed. In aged mice, LIPUS significantly increased gastrocnemius muscle mass and upregulated Fndc5 and Opa1 mRNA, genes associated with mitochondrial function and muscle regeneration. These findings suggest that LIPUS may serve as a safe, non-invasive intervention to counteract sarcopenia by promoting muscle growth and mitochondrial gene activation in aged skeletal muscle.

In the context of increasing life expectancy, a higher prevalence of age-related chronic diseases is becoming more common in the health landscape, many of which are closely linked to insufficient physical exercise during lifespan. On the other hand, aging is also associated with damage to various molecules, including DNA, by reactive oxygen species. Given that both senescence and muscle mass loss are intimately linked to increased levels of DNA damage and deterioration of antioxidant defense, this systematic review aims to evaluate whether regular physical exercise could indeed induce genotoxicity and to assess the quality of published articles on this topic. To achieve this objective, a total of 16 selected studies were meticulously analyzed by three experienced reviewers, who assigned scores to each study based on predetermined analysis parameters. Our results revealed that there is no consensus in the literature regarding genotoxicity induced by regular physical activity in older adults, regardless of the type, volume and intensity of exercise performed. In terms of quality assessment, 11 studies (out of 16) were categorized as Strong or Moderate, thus we consider our findings to be reliable. Undoubtedly, these findings are crucial for elucidating the role of regular physical exercise on genotoxicity-related biomarkers in older adults.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare and fatal disorder characterized by premature aging, predominantly resulting from mutations in the LMNA gene, which lead to the accumulation of a truncated and aberrant progerin protein. This paper offers an in-depth review of the fundamental theories, epidemiology, pathological mechanisms, and treatment strategies associated with HGPS as caused by LMNA gene mutations. Furthermore, it examines the current challenges in clinical translation, with the objective of providing a comprehensive reference for research and therapeutic development in the field of HGPS.

Circadian time keeping system (CTS) consisting of network of central and peripheral clocks regulates physiological, metabolic, and behavioural processes in alignment with the 24 hour. Desynchrony between central and peripheral clocks contributes to the pathogenesis of age-related conditions such as metabolic syndrome, cognitive decline, immune dysfunction, and neurodegenerative diseases etc. Sex-specific susceptibilities further modulate circadian resilience, with hormonal changes and redox imbalances playing key roles in the aging trajectory. Immune senescence and hormonal dampening, particularly in cortisol and melatonin rhythms, exacerbate circadian misalignment, accelerating systemic decline with aging. Interestingly, aging and clock dysfunction is a bidirectional process, i.e. aging progressively influences circadian rhythms across multiple levels and vice versa, from the molecular architecture of core clock gene feedback loops to the functionality of the central pacemaker-the suprachiasmatic nucleus (SCN)-and its coordination with peripheral oscillators. This review critically highlights the complex alterations in circadian mechanisms associated with aging, including diminished transcriptional rhythmicity, epigenetic drift, mitochondrial desynchronization, and disruptions in neurotransmitter systems. Such changes in turn leads to weakened SCN output, impaired photic entrainment, and loss of temporal coherence across organ systems. Further, this review demonstrates CTS and aging at multiple levels such as behavioural, physiological, biochemical and molecular levels are linked in push-pull mechanism i.e., the breakdown in the harmony of circadian rhythms at systemic level pushes the organism towards early aging and aging in turn is linked to CTS disorders.

Sleep deprivation (SD) and aging are linked to chronic inflammation, a contributor to age-associated diseases. Circadian rhythms, governed by suprachiasmatic nucleus (SCN), regulate immune and inflammatory responses. While aging and SD elevate pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6, their impact on temporal dynamics of inflammation across tissues and age groups remains unclear. This study examines age-dependent effects of chronic total SD on daily expression rhythms of inflammatory markers in central (SCN) and peripheral (cerebral cortex, liver, intestine) clocks of male Wistar rats aged 3 (adult), 12 (middle-aged), and 24 (old) months (m). Nitric oxide (NO), linked to inflammation and metabolism, was also evaluated in liver and intestine. Animals were sampled at four Zeitgeber (ZT) times. Further, the study examined the effects of melatonin, a circadian-regulated antioxidant, anti-inflammatory agent, and sleep synchronizer, on daily rhythms of inflammatory markers with aging and upon SD were studied. The mRNA expression levels of rTnf-α, rIl-6 and rIl-1β were assessed using qRT-PCR. NO levels were measured using Griess assay. Rats were grouped as control, SD, SD + melatonin and vehicle control groups. Significant SD-induced misalignment, especially in rIl-6 and rTnf-α in cerebral cortex and liver was observed in 12 m. SD altered circadian phases and expression levels were significantly greater in older rats (24 m > 12 m > 3 m) and in peripheral clock as compared to central clock liver > cerebral cortex > intestine > SCN. Melatonin differentially restored these rhythms, most effectively for rIl-1β and in the cerebral cortex and liver. SCN showed highest resilience, reinforcing its role as the central circadian pacemaker, while the liver and cerebral cortex emerged as the most vulnerable to SD and aging.

Aging is characterized as a process resulting in the structural and functional deterioration of several essential organs and tissues. This study aimed to determine the effects of normal aging on the cerebellum by using histological and histometric techniques. A total of 24 male Wistar albino rats were divided into three groups: young (4-6 weeks), adult (20-22 weeks), and old (22-24 months). Cerebellar tissue samples were treated using histological and immunohistochemical techniques. The slides were evaluated using a light microscope. Molecular layer thickness was high in the adult group compared to the younger and older groups, whereas the granular layer was significantly thicker in both the adult and elderly groups than in the young rat group (P < 0.05). The total cortical thickness exhibited statistically significant differences among all age groups. The thickest cortex was observed in the adult group (P < 0.05). PAS-positive aging pigment granules were observed in the cytoplasm of Purkinje cells in older rat groups. The density of glial fibrillary acidic protein-immunoreactive (GFAP-IR) astrocytes in old rats was significantly increased compared to young and adult rats with distinct hypertrophy and strong GFAP immunoreactivity in astrocyte cell bodies. It was established that, despite age-related variations that exist, cerebellar folia height and width gradually increased from young to adult rat. In contrast, old rats have decreased cerebellar folia height and width than adults.

The progressive functional decline associated with aging is a primary risk factor for numerous chronic diseases. The discovery of natural compounds that can modulate conserved longevity pathways offers a promising strategy for promoting healthy aging. Hyperoside, a flavonoid abundant in edible plants such as hawthorn, possesses various pharmacological activities, but its specific role and molecular mechanisms in geroprotection remain poorly understood. This study aimed to elucidate the anti-aging effects of hyperoside and its underlying mechanisms using the model organism Caenorhabditis elegans (C. elegans). Our results showed that hyperoside treatment significantly extended the mean lifespan of wild-type C. elegans by up to 19.97% and robustly enhanced healthspan by improving motility and reducing the accumulation of the aging biomarker lipofuscin. Hyperoside could also alleviate Parkinsonism in neurodegeneration models, without disrupting lipid homeostasis or reproduction. Furthermore, hyperoside conferred increased resistance to thermal, oxidative, and pathogenic stress. Mechanistically, the lifespan-extending effects of hyperoside requires the transcription factors DAF-16/FOXO, SKN-1/Nrf2, and HSF-1, and factors involved in immune and anti-oxidative response, including the MAPKK SEK-1 and p38 MAPK PMK-1. Hyperoside treatment promoted the nuclear translocation of DAF-16 and SKN-1 and upregulated their respective downstream target genes, including sod-3 and gst-4. Hyperoside also increased the expression of genes that are the downstream target of both PMK-1 and SKN-1. Since the role of SKN-1 in immune and anti-oxidative response were regulated by PMK-1. Therefore, the beneficial effects of hyperoside might be mediated primarily by activating SEK-1 /PMK-1/ SKN-1 pathway, which subsequently activate HSF-1 to maintain proteostasis. These findings underscore the potential of hyperoside as a dietary-derived agent for combating age-related functional decline.