bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2024–12–29
thirty-six papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño



  1. Exp Hematol. 2024 Dec 24. pii: S0301-472X(24)00562-9. [Epub ahead of print] 104698
      Aging exerts a profound impact on the hematopoietic system, leading to increased susceptibility to infections, autoimmune diseases, chronic inflammation, anemia, thrombotic events, and hematologic malignancies. Within the field of experimental hematology, the functional decline of hematopoietic stem cells (HSCs) is often regarded as a primary driver of age-related hematologic conditions. However, aging is clearly a complex multifaceted process involving not only HSCs but also mature blood cells and their interactions with other tissues. This review reappraises an HSC-centric view of hematopoietic aging by exploring how the entire hematopoietic hierarchy, from stem cells to mature cells, contributes to age-related disorders. It highlights the decline of both innate and adaptive immunity, leading to increased susceptibility to infections and cancer, and the rise of autoimmunity as peripheral immune cells undergo aging-induced changes. It explores the concept of "inflammaging," where persistent, low-grade inflammation driven by old immune cells creates a cycle of tissue damage and disease. Additionally, this review delves into the roles of inflammation and homeostatic regulation in age-related conditions such as thrombotic events and anemia, arguing that these issues arise from broader dysfunctions rather than stemming from HSC functional attrition alone. In summary, this review highlights the importance of taking a holistic approach to studying hematopoietic aging and its related pathologies. By looking beyond just stem cells and considering the full spectrum of age-associated changes, one can better capture the complexity of aging and attempt to develop preventative or rejuvenative strategies that better target multiple facets of this process.
    Keywords:  CHIP; HSC; Hematopoietic stem cells; Inflammation; aging; anemia; clonal hematopoiesis; immune compromised; inflammaging; myeloid bias
    DOI:  https://doi.org/10.1016/j.exphem.2024.104698
  2. Arch Pharm Res. 2024 Dec 26.
      Immunosenescence is a weakening of the immune system due to aging, characterized by changes in immune cells and dysregulated immune function. Age-related immune cells are increasing with aging. They are associated with chronic prolonged inflammation, causing tissue dysfunction and age-related diseases. Here, we discuss increased pro-inflammatory activity of aged macrophages, accumulation of lymphocytes with an age-associated phenotype, and specific alterations in both functions and characteristics of these immune cells. These cellular changes are associated with development of age-related diseases. Additionally, we reviewed various therapeutic strategies targeting age-related immunosenescence, providing pathways to mitigate effects of age-related diseases.
    Keywords:  Age-related diseases; Aging; Immune cell; Immunosenescence
    DOI:  https://doi.org/10.1007/s12272-024-01529-7
  3. Front Aging Neurosci. 2024 ;16 1450337
       Background: It is been noted that the expression levels of numerous genes undergo changes as individuals age, and aging stands as a primary factor contributing to age-related diseases. Nevertheless, it remains uncertain whether there are common aging genes across organs or tissues, and whether these aging genes play a pivotal role in the development of age-related diseases.
    Methods: In this study, we screened for aging genes using RNAseq data of 32 human tissues from GTEx. RNAseq datasets from GEO were used to study whether aging genes drives age-related diseases, or whether anti-aging solutions could reverse aging gene expression.
    Results: Aging transcriptome alterations showed that brain aging differ significantly from the rest of the body, furthermore, brain tissues were divided into four group according to their aging transcriptome alterations. Numerous genes were downregulated during brain aging, with functions enriched in synaptic function, ubiquitination, mitochondrial translation and autophagy. Transcriptome analysis of age-related diseases and retarding aging solutions showed that downregulated aging genes in the hippocampus further downregulation in Alzheimer's disease but were effectively reversed by high physical activity. Furthermore, the neuron loss observed during aging was reversed by high physical activity.
    Conclusion: The downregulation of many genes is a major contributor to brain aging and neurodegeneration. High levels of physical activity have been shown to effectively reactivate these genes, making it a promising strategy to slow brain aging.
    Keywords:  aging gene; brain aging; neurodegenerative diseases; retard aging; transcriptome
    DOI:  https://doi.org/10.3389/fnagi.2024.1450337
  4. Biosci Biotechnol Biochem. 2024 Dec 26. pii: zbae205. [Epub ahead of print]
      Intrinsic skin aging is a chronological decline in skin texture and function influenced largely by genetic factors. Aged skin exhibits morphological alterations, including wrinkling, dryness, and roughness, along with dysfunctional changes in the skin barrier. In this study, the in vivo anti-intrinsic aging efficacy of dietary astaxanthin extracted from Haematococcus pluvialis on the skin was evaluated using aged C57BL/6 J mice. As a result, dietary supplementation of 0.1% astaxanthin significantly alleviated the defects in skin's water retention capacity, viscoelasticity, and reduced wrinkle formation induced by intrinsic aging. Furthermore, gene expression analysis revealed that dietary astaxanthin was capable of mediating genes related to the proliferation and differentiation of skin cells, degradation of proteins in the extracellular matrix and dermal-epidermal junction, synthesis of natural moisturizing factors, and maintenance of skin barrier function. Together, our data indicate that dietary astaxanthin has potential applications as a novel ingredient in nutricosmetics against chronological skin aging.
    Keywords:  astaxanthin; carotenoid; dietary supplementation; intrinsic skin aging; skin barrier function
    DOI:  https://doi.org/10.1093/bbb/zbae205
  5. NPJ Sci Food. 2024 Dec 24. 8(1): 111
      Artemisia argyi Lévl. et Vant. (A. argyi) leaf possesses various health promoting functions contributed by its main bioactive flavonoids. In this study, the anti-aging effect and mechanism of Artemisia argyi leaf extract (AALE) were identified using Caenorhabditis elegans (C. elegans) as a model. The results showed that the AALE promoted the lifespan and stress resistance of C. elegans. It was found that the AALE boosted the expression of oxidative stress-related proteins by regulating the insulin/ IGF-1 signaling (IIS) pathway, which then activated the transcription factors DAF-16/FOXO. The results of RNA-sequence analysis indicated that the changes of genes in nematodes treated with AALE were associated with the responses against oxidative stress, cell maturation, and immune reaction, and stress. The positive results suggest that Artemisia argyi leaf could have the robust benefits for improving healthy aging as well as preventing aging-related diseases in the human body.
    DOI:  https://doi.org/10.1038/s41538-024-00358-8
  6. J Gerontol A Biol Sci Med Sci. 2024 Dec 23. pii: glae299. [Epub ahead of print]
      Calorie restriction (CR) extends lifespan and prevents several aging related diseases. During short-term restriction, we previously showed that lean tissues generally decrease in size, but the alimentary tract (especially the stomach) grows. To illuminate pathway alterations in these contrasting tissues we compared gene expression profiles (bulk RNAseq) of the skeletal muscle and stomach, in the same male C57BL/6J mice exposed to 3 months of graded CR (0-40%). Transcriptomic analysis showed the numbers of differentially expressed genes (DEGs) relative to 12h ad libitum (12AL) feeding increased as the level of restriction increased. We found the canonical CR and aging related pathways, eukaryotic translation initiation factor 2 (EIF2) and mammalian target of rapamycin (mTOR), were significantly up- and downregulated respectively in gastrocnemius muscle, but less so in the stomach. These changes were consistent with the differential growth status of the two tissues under CR. However, various immune-related pathways such as pathogenesis of influenza and interferon signalling pathway were downregulated and the PD-1/PD-L1 cancer immunotherapy pathway was upregulated with increased CR level in the stomach, indicating an impaired ability of anti-virus and improvement of cancer treatment. Furthermore, in the mTOR and NF-kB aging related pathways, more genes in muscle tissue were significantly correlated with CR level than in the stomach and liver. Suggesting muscle is an important aging related tissue responding to caloric restriction. These two pathways were altered in a manner consistent with increased lifespan as CR level increased in both tissues.
    Keywords:  RNAseq; calorie restriction; skeletal muscle; stomach
    DOI:  https://doi.org/10.1093/gerona/glae299
  7. Aging Cell. 2024 Dec 25. e14446
      Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies due to their self-renewal and differentiation capabilities. Pathological microenvironments expose MSCs to senescence-inducing factors such as reactive oxygen species (ROS), resulting in MSC functional decline and loss of stemness. Oxidative stress leads to mitochondrial dysfunction, a hallmark of senescence, and is prevalent in aging tissues characterized by elevated ROS levels. We hypothesized that overexpression of nuclear respiratory factor-1 (NRF1), a driver of mitochondrial biogenesis, could metabolically potentiate MSCs and prevent MSC senescence. Single-cell RNA sequencing (scRNA-Seq) revealed that MSCs transfected with NRF1 messenger RNA (mRNA) exhibited upregulated expression of genes associated with oxidative phosphorylation (OXPHOS), decreased glycolytic markers, and suppression of senescence-related pathways. To test whether NRF1 induction could mitigate stress-induced premature senescence, we exposed MSCs to hydrogen peroxide (H2O2) and validated our findings in a replicative senescence model. NRF1 mRNA transfection significantly increased mitochondrial mass and improved aberrant mitochondrial processes associated with senescence, including reduced mitochondrial and intracellular total ROS production. Mitochondrial health and dynamics were preserved, and respiratory function was restored, as evidenced by enhanced OXPHOS, reduced glycolysis, and increased ATP production. Notably, NRF1 overexpression led to decreased senescence-associated β-galactosidase (SA-β-gal) activity and reduced expression of senescence markers p53, p21, and p16. Our findings demonstrate that NRF1 induction attenuates MSC senescence by enhancing mitochondrial function, suggesting potential translational applications for MSC-based therapies and senescence-targeted interventions.
    Keywords:  mesenchymal stem cells; mitochondrial biogenesis; mitochondrial dysfunction; nuclear respiratory factor‐1 (NRF1); oxidative stress; senescence
    DOI:  https://doi.org/10.1111/acel.14446
  8. J Biochem. 2024 Dec 27. pii: mvae091. [Epub ahead of print]
      Cellular senescence, which entails cellular dysfunction and inflammatory factor release-the senescence-associated secretory phenotype (SASP)-is a key contributor to multiple disorders, diseases, and the geriatric syndromes. Targeting senescent cells using senolytics has emerged as a promising therapeutic strategy for these conditions. Among senolytics, the combination of dasatinib and quercetin (D + Q) was the earliest and one of the most successful so far. D + Q delays, prevents, alleviates, or treats multiple senescence-associated diseases and disorders with improvements in healthspan across various preclinical models. While early senolytic therapies have demonstrated promise, ongoing research is crucial to refine them and address such challenges as off-target effects. Recent advances in senolytics include new drugs and therapies that target senescent cells more effectively. The identification of senescence-associated antigens-cell surface molecules on senescent cells-pointed to another promising means for developing novel therapies and identifying biomarkers of senescent cell abundance.
    Keywords:  Cell surface proteins; Cellular senescence; Immunotherapy; Seno-antigens; Senolytics
    DOI:  https://doi.org/10.1093/jb/mvae091
  9. Metabolites. 2024 Dec 19. pii: 716. [Epub ahead of print]14(12):
       BACKGROUND: Aging and age-related diseases are closely linked to an imbalance in energy supply and demand, a condition that can potentially be mitigated through various interventions, including the use of naturally occurring molecules. Norathyriol (NL), a tetrahydroxyxanthone compound, is prevalent in mango fruit and medicinal plants. While studies have indicated that NL may influence metabolism, its effects on aging have not been extensively explored.
    METHODS: We conducted lifespan analysis and measured lipofuscin accumulation in C. elegans model to evaluate the effects of NL on aging. Additionally, we identified differentially expressed genes (DEGs) through comprehensive RNA-sequencing (RNA-seq) analysis and performed gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGGs) pathway analyses to elucidate the molecular mechanisms underlying NL's effects.
    RESULTS: Our study demonstrated that NL at 50 μM extends the lifespan by 15.9% and reduces lipofuscin accumulation in C. elegans without impacting their feeding capabilities. A total of 928 DEGs were identified in NL-treated worms. The analysis of DEGs indicated that NL's longevity-promoting effects might be due to its regulation of gene expression in lipid metabolism and immune response pathways. Furthermore, the insulin/insulin-like growth factor (IGF)-1 and target of rapamycin (TOR) signaling pathways were implicated in the lifespan-extending effect of NL.
    CONCLUSIONS: These findings broaden the bioactivity profile of polyphenols and highlight the need for further investigation into the therapeutic potential of NL in combating age-related diseases.
    Keywords:  C. elegans; aging; lipid metabolism; norathyriol; transcriptome analysis
    DOI:  https://doi.org/10.3390/metabo14120716
  10. Aging Cell. 2024 Dec 27. e14462
      Aging is accompanied by multiple molecular changes that contribute to aging associated pathologies, such as accumulation of cellular damage and mitochondrial dysfunction. Tissue metabolism can also change with age, in part, because mitochondria are central to cellular metabolism. Moreover, the cofactor NAD+, which is reported to decline across multiple tissues during aging, plays a central role in metabolic pathways such as glycolysis, the tricarboxylic acid cycle, and the oxidative synthesis of nucleotides, amino acids, and lipids. To further characterize how tissue metabolism changes with age, we intravenously infused [U-13C]-glucose into young and old C57BL/6J, WSB/EiJ, and diversity outbred mice to trace glucose fate into downstream metabolites within plasma, liver, gastrocnemius muscle, and brain tissues. We found that glucose incorporation into central carbon and amino acid metabolism was robust during healthy aging across these different strains of mice. We also observed that levels of NAD+, NADH, and the NAD+/NADH ratio were unchanged in these tissues with healthy aging. However, aging tissues, particularly brain, exhibited evidence of upregulated fatty acid and sphingolipid metabolism reactions that regenerate NAD+ from NADH. These data suggest that NAD+-generating lipid metabolism reactions may help to maintain the NAD+/NADH ratio during healthy aging.
    Keywords:  NAD; aging; metabolic rate; mice
    DOI:  https://doi.org/10.1111/acel.14462
  11. Cell Mol Gastroenterol Hepatol. 2024 Dec 19. pii: S2352-345X(24)00198-X. [Epub ahead of print] 101443
      Intestinal stem cells replenish the epithelium throughout life by continuously generating intestinal epithelial cell types, including absorptive enterocytes, and secretory goblet, endocrine, and Paneth cells. This process is orchestrated by a symphony of niche factors required to maintain intestinal stem cells and to direct their proliferation and differentiation. Among the various mature intestinal epithelial cell types, Paneth cells are unique in their location in the stem cell zone, directly adjacent to intestinal stem cells. Although Paneth cells were first described as an epithelial cell component of the innate immune system due to their expression of anti-microbial peptides, they have been proposed to be niche cells due to their close proximity to intestinal stem cells and expression of niche factors. However, function as a niche cell has been debated since mice lacking Paneth cells retain functional stem cells that continue to replenish the intestinal epithelium. In this review, we summarize the intestinal stem cell niche, including the Notch, Wnt, growth factor, mechanical, and metabolic niche, and discuss how Paneth cells might contribute to these various components. We also present a nuanced view of the Paneth cell as a niche cell. Although not required, Paneth cells enhance stem cell function, particularly during intestinal development and regeneration. Furthermore, we suggest that Paneth cell loss induces ISC remodeling to adjust their niche demands.
    Keywords:  Intestinal crypt; Notch signaling; WNT signaling; cellular remodeling; tissue regeneration
    DOI:  https://doi.org/10.1016/j.jcmgh.2024.101443
  12. J Gerontol A Biol Sci Med Sci. 2024 Dec 21. pii: glae298. [Epub ahead of print]
      Aging and age-related cognitive impairment have emerged as a growing global public health concern and remain no effective preventive strategies. Excessive oxidative stress and neuroinflammation have been proven to contribute to cognitive decline. Vitamin D maintains the redox balance and exerts immunomodulatory effects, but the specific role of vitamin D in aging and age-related cognitive impairment remains elusive. This study explored the neuroprotective effects and the potential molecular mechanisms of 1α,25-Dihydroxyvitamin D3 in the aging model. An aging model was established by the treatment of D-galactose for 14 weeks in Male KM mice. 0.1, 0.5, or 1 μg/kg 1α,25-Dihydroxyvitamin D3 were used in the intervention group for 8 weeks. Cognitive performance was evaluated using the Morris water maze test, and the levels of oxidative stress and neuroinflammation in the hippocampus were further analyzed. D-galactose induced memory impairment, whereas 1α,25-Dihydroxyvitamin D3 intervention prevented cognitive decline, accompanied by a reduction in neuronal apoptosis, an enhancement of synaptic plasticity, and a decrease in Aβ deposition. Meanwhile, 1α,25-Dihydroxyvitamin D3 dramatically attenuated oxidative stress, mitigated microglial cell activation, and ameliorated neuroinflammation by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (AREs) axis and inhibiting the NF-κB signaling pathway. This study provides evidence that 1α,25-Dihydroxyvitamin D3 might be a promising nutritional strategy for preventing cognitive decline in aging, thereby facilitating the clinical application and expanding the insight of vitamin D.
    Keywords:  aging; cognitive impairment; neuroinflammation; oxidative stress; vitamin D
    DOI:  https://doi.org/10.1093/gerona/glae298
  13. Geroscience. 2024 Dec 27.
      Paroxetine, a selective serotonin reuptake inhibitor, is widely used in the clinical treatment of depression. While several antidepressants show promise as geroprotectors, the role of paroxetine in aging remains unclear. In this study, we evaluated the lifespan extension effect of paroxetine in Caenorhabditis elegans (C. elegans) and elucidated the underlying mechanisms. The results showed that paroxetine can prolong lifespan concomitant extension of healthspan as indicated by increasing mobility and reducing lipofuscin accumulation, as well as confer protection to nematodes against different abiotic stresses. Paroxetine upregulated ser-7 expression and downregulated dop-4 expression. dop-4 RNA interference (RNAi) mimicked the beneficial effect of paroxetine on lifespan. Conversely, ser-7 RNAi abolished paroxetine-induced lifespan extension and the expression changes of dop-4 and genes related to insulin/insulin-like growth factor 1 signaling (IIS). Moreover, paroxetine exhibited a comparable lifespan extension effect to that observed in daf-2 or age-1 mutants; however, this effect was abolished in daf-16 mutant. Taken together, these results suggest that paroxetine promotes health and longevity in C. elegans through the ser-7-dop-4-IIS pathway, underscoring its potential as a geroprotector.
    Keywords:   Caenorhabditis elegans ; Aging; Lifespan; Paroxetine
    DOI:  https://doi.org/10.1007/s11357-024-01492-7
  14. Food Funct. 2024 Dec 23.
      Astaxanthin is a xanthophyll carotenoid which has been associated with a number of health-promoting effects, including anti-aging; however, the underlying mechanisms are not fully understood. In the present study, it was found that astaxanthin promoted the longevity of wild-type (N2) Caenorhabditis elegans (C. elegans). The lifespan-extending effect of astaxanthin was associated with a significant decrease of lipofuscin accumulation and the reduction of the age-related decline in spontaneous motility. Meanwhile, astaxanthin enhanced the oxidative stress resistance in C. elegans, preventing the elevation of the reactive oxygen species and alleviating juglone-induced toxicity. Further studies revealed that astaxanthin treatment induced the expression of the skn-1 gene; besides, the lifespan-extending effect of astaxanthin relied on SKN-1. Additionally, the expression of age-1, a PI3K homolog gene, and let-363, a target of the rapamycin (TOR) homolog gene, was decreased, while the expression of PHA-4, a transcription factor negatively regulated by TOR signaling, was increased by astaxanthin treatment. PHA-4 has been demonstrated to regulate the expression of genes playing critical roles in the autophagy-lysosome pathway (ALP). Consistently, several key genes related to ALP, including lgg-1, atg-5, vps-34, ncr-1 and asm-1 were upregulated in C. elegans treated with astaxanthin. Knockdown of pha-4 expression by siRNA prevented the elevation of the above ALP-related genes, while diminishing the lifespan-extension effect of astaxanthin. Overall, these results indicated that astaxanthin prolonged the lifespan of C. elegans via modulating the intracellular redox status and promoting PHA-4-mediated autophagy.
    DOI:  https://doi.org/10.1039/d4fo03490b
  15. Aging Cell. 2024 Dec 27. e14459
      Despite advances in understanding molecular and cellular changes in the aging nervous system, the upstream drivers of these changes remain poorly defined. Here, we investigate the roles of non-neural tissues in neuronal aging, using the cutaneous PVD polymodal sensory neuron in Caenorhabditis elegans as a model. We demonstrate that during normal aging, PVD neurons progressively develop excessive dendritic branching, functionally correlated with age-related proprioceptive deficits. Our study reveals that decreased collagen expression, a common age-related phenomenon across species, triggers this process. Specifically, loss-of-function in dpy-5 or col-120, genes encoding cuticular collagens secreted to the epidermal apical surface, induces early-onset excessive dendritic branching and proprioceptive deficits. Adulthood-specific overexpression of dpy-5 or col-120 mitigates excessive branching in aged animals without extending lifespan, highlighting their specific roles in promoting neuronal health span. Notably, collagen reduction specifically drives excessive branching in select sensory neuron subclasses but does not contribute to PVD dendritic beading, another aging-associated neurodegenerative phenotype associated with distinct mechanosensitive dysfunction. Lastly, we identify that rig-3, an immunoglobulin superfamily member expressed in interneurons, acts upstream of collagen genes to maintain PVD dendritic homeostasis during aging, with collagen's regulatory role requiring daf-16/FOXO. These findings reveal that age-related collagen reduction cues neuronal aging independently of collagen's traditional structural support function, possibly involving bi-directional communication processes between neurons and non-neuronal cells. Our study also offers new insights into understanding selective neuron vulnerability in aging, emphasizing the importance of multi-tissue strategies to address the complexities of neuronal aging.
    Keywords:   Caenorhabditis elegans ; aging; collagen; epidermis; neuronal aging; sensory neurons
    DOI:  https://doi.org/10.1111/acel.14459
  16. Nat Aging. 2024 Dec 27.
      Although senescent cells can be eliminated by the immune system, they tend to accumulate with age in various tissues. Here we show that senescent cells can evade immune clearance by natural killer (NK) cells by upregulating the expression of the disialylated ganglioside GD3 at their surface. The increased level of GD3 expression on senescent cells that naturally occurs upon aging in liver, lung, kidney or bones leads to a strong suppression of NK-cell-mediated immunosurveillance. In mice, we found that targeting GD3+ senescent cells with anti-GD3 immunotherapy attenuated the development of experimentally induced or age-related lung and liver fibrosis and age-related bone remodeling. These results demonstrate that GD3 upregulation confers immune privilege to senescent cells. We propose that GD3 acts as a senescence immune checkpoint (SIC) that allows senescent cells to escape immunosurveillance and to trigger immune anergy during aging.
    DOI:  https://doi.org/10.1038/s43587-024-00776-z
  17. Front Pharmacol. 2024 ;15 1510307
       Background: Astragalus mongholicus Bunge [Fabaceae; Astragali radix] (AM), a traditional Chinese medicinal (TCM) botanical drug, has been used for centuries and is gaining growing recognition in medical research for its therapeutic potential. The currently accepted scientific name is Astragalus mongholicus Bunge, with Astragalus membranaceus Fisch. ex Bunge recognized as a taxonomic synonym. This review explores the most relevant scientific studies on AM, focusing on its chemical composition, mechanisms of action, and associated health benefits.
    Main body: AM is commonly used in clinical practice to treat diabetes mellitus, cardiovascular diseases, oncological processes, lipid metabolism disorders, and ulcerative colitis. Recent research has investigated its potential as a product for anti-aging purposes. These therapeutic effects are attributed to the interactions of bioactive metabolites such as Astragaloside IV, Formononetin, and polysaccharides, with various signaling pathways, leading to the activation or inhibition of gene expression. This review aims to map the signaling pathways affected by these metabolites and their effects on different pathologies. Studies suggest that these metabolites act on signaling pathways such as TLR4/MyD88/NF-κB, PI3K/AKT, RNA expression, and tumor receptors. However, further research is necessary to validate the findings in human trials with better methodological quality.
    Conclusion: AM is rich in bioactive metabolites that interact with various signaling pathways, modulating diseases such as diabetes mellitus type 2, cardiovascular diseases, cancer, lipid metabolism disorders, and ulcerative colitis. Although promising, the majority of the studies are conducted in vitro and animal models, and more rigorous human trials are needed to determine the therapeutic potential of AM.
    Keywords:  Astragalus mongholicus; astragaloside IV; formononetin; polysaccharides; signaling pathways
    DOI:  https://doi.org/10.3389/fphar.2024.1510307
  18. Adv Sci (Weinh). 2024 Dec 25. e2413122
      Promoting tumor cell senescence arrests the cell cycle of tumor cells and activates the immune system to eliminate these senescent cells, thereby suppressing tumor growth. Nevertheless, PD-L1 positive senescent tumor cells resist immune clearance and possess the ability to secret various cytokines and inflammatory factors that stimulate the growth of tumor cells. Consequently, drugs capable of both triggering senescence in tumor cells and concurrently diminishing the expression of PD-L1 to counteract immune evasion are urgently needed. Here, a berberine derivative B68 is developed, which specifically induces tumor cell senescence by targeting BMI1. B68 also involves the degradation of PD-L1 by targeting CSN5, thereby disrupting the immunosuppressive PD-1/PD-L1 interaction and enabling rapid clearance of senescent tumor cells. This approach simultaneously inhibits tumor progression and activates T cell immunity, as evidenced by the robust antitumor response following B68-induced immunization of senescent cancer cells. Moreover, the synergistic effect of B68 with anti-CTLA4 therapy further enhances antitumor immunity, and its ability to induce senescence in cancer cells triggers a strong protective response by dendritic and CD8+ T cells. These findings provide a scientific basis for developing a new tumor treatment strategy based on senescence induction and lay the foundation for further preclinical research.
    Keywords:  BMI1; CSN5; PD‐L1; colorectal cancer; tumor cell senescence
    DOI:  https://doi.org/10.1002/advs.202413122
  19. J Cosmet Dermatol. 2024 Dec 24. e16749
       BACKGROUND: Myoelectrical stimulation improves muscle function and reduces muscle atrophy and aging. However, research on the mechanism underlying its cosmetic effect remains limited.
    AIMS: The aim of this study was to evaluate the cosmetic effects of the myoelectrical stimulation provided by the wearable intelligent flexible beauty device and its focused electric field technology (FEFT) on facial skin and muscle rejuvenation.
    PATIENTS/METHODS: We conducted a single-blind, randomized, self-controlled clinical efficacy experiment on 31 female volunteers using the device. Using an FEFT-based platform, mice with d-galactose-induced skeletal muscle aging were subjected to surface myoelectrical stimulation of the gastrocnemius. Immunohistochemical analysis of skeletal muscles and protein immunoblotting were used to analyze the effects of FEFT.
    RESULTS: After 14 days of use, facial skin elasticity significantly increased, wrinkle firmness significantly decreased, and the lift height of the upper eyelid and eye corner angle significantly increased in the volunteers. Clinical evaluation showed improvements in the drooping of the upper eyelid and eye bags. Self-evaluation questionnaires indicated alleviation of facial wrinkles. These improvements were more pronounced after 28 days. In mice, FEFT alleviated aging-induced muscle fiber atrophy, muscle fiber cross-sectional area reduction, and muscle satellite cell loss. FEFT also increased the expression of myogenic factors, including myogenic differentiation 1 (MYOD1).
    CONCLUSIONS: FEFT exerted a skin-tightening effect by initiating myogenic processes and increasing the transformation of muscle satellite cells. Our research promotes the development of FEFT-based medical rehabilitation or cosmetic anti-aging products and provides a foundation for further application and comprehensive efficacy evaluation in human clinical settings.
    Keywords:  clinical evaluation; muscle aging; muscle satellite cells; myoelectrical stimulation; myogenic regulatory family; wearable electronic devices
    DOI:  https://doi.org/10.1111/jocd.16749
  20. J Mol Med (Berl). 2024 Dec 21.
      Adipose-derived stem cells (ADSCs) have become one of the best seed cells widely studied and concerned in tissue engineering because of their rich sources and excellent multi-directional differentiation ability, which are expected to play a practical application role in tissue defect, osteoporosis, plastic surgery, and other fields. However, the differentiation direction of ADSCs is regulated by complex factors. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 500 nucleotides that do not encode proteins and can act as signaling RNAs in response to intracellular and extracellular stimuli. Recently, accumulating evidence has revealed that lncRNAs could regulate the cell cycle and differentiation direction of ADSCs through various mechanisms, including histone modification, binding to RNA-binding proteins, and regulating the expression of miRNAs. Therefore, enriching and elucidating its mechanism of action as well as targeting lncRNAs to regulate ADSCs differentiation have potential prospects in tissue regeneration applications such as bone, blood vessels, and adipose. In this review, we summarize the role and mechanism of lncRNAs and its complexes in the multi-directional differentiation of ADSCs and discuss some potential approaches that can exert therapeutic effects on tissue defects by modulating the expression level of lncRNAs in ADSCs. Our work might provide some new research directions for the clinical applications of tissue engineering.
    Keywords:  Adipose-derived stem cells; Differentiation; Long non-coding RNA; Tissue regeneration
    DOI:  https://doi.org/10.1007/s00109-024-02507-8
  21. Am J Physiol Cell Physiol. 2024 Dec 26.
      Cellular senescence has been implicated in the aging-related dysfunction of satellite cells, the resident muscle stem cell population primarily responsible for the repair of muscle fibres. Despite being in a state of permanent cell cycle arrest, these cells remain metabolically active and release an abundance of factors that can have detrimental effects on the cellular microenvironment. This phenomenon is known as the senescence-associated secretory phenotype (SASP), and its metabolic profile is poorly characterized in senescent muscle. In the present investigation, we examined the intracellular and extracellular metabolome of C2C12 myoblasts using a bleomycin-mediated model of DNA damage-induced senescence. We also evaluated the relationship between the senescent metabolic phenotype and SASP signalling through molecular and network-based analyses. Senescent myoblasts exhibited a significantly altered extracellular metabolome (i.e. exometabolome), including increased secretion of several aging-associated metabolites. Four of these metabolites - trimethylamine-N-oxide (TMAO), xanthine, choline, and oleic acid - were selected for individual dose-response experiments to determine if they could drive the senescence phenotype. While most of the tested metabolites did not independently alter senescence markers, oleic acid treatment of healthy myoblasts significantly upregulated the SASP genes Ccl2, Cxcl12, and Il33 (p<0.05). A gene-metabolite interaction network further revealed that oleic acid was one of the most interconnected metabolites to key senescence-associated genes. Notably, oleic acid interacted with several prominent SASP genes, suggesting a potential epigenetic effect between this monounsaturated fatty acid and SASP regulation. In summary, the exometabolome, particularly oleic acid, is implicated in SASP signalling within senescent myoblasts.
    Keywords:  SASP; metabolome; myoblast; senescence; skeletal muscle
    DOI:  https://doi.org/10.1152/ajpcell.00880.2024
  22. Bioessays. 2024 Dec 26. e202400216
      Myotonic dystrophy type 1 (DM1) is considered a progeroid disease (i.e., causing premature aging). This hypervariable disease affects multiple systems, such as the musculoskeletal, central nervous, gastrointestinal, and others. Despite advances in understanding the underlying pathogenic mechanism of DM1, numerous gaps persist in our understanding, hindering elucidation of the heterogeneity and severity of its symptoms. Accumulating evidence indicates that the toxic intracellular RNA accumulation associated with DM1 triggers cellular senescence. These cells are in a state of irreversible cell cycle arrest and secrete a cocktail of cytokines, referred to as a senescence-associated secretory phenotype (SASP), that can have harmful effects on neighboring cells and more broadly. We hypothesize that cellular senescence contributes to the pathophysiology of DM1, and clearance of senescent cells is a promising therapeutic approach for DM1. We will discuss the therapeutic potential of different senotherapeutic drugs, especially senolytics that eliminate senescent cells, and senomorphics that reduce SASP expression.
    Keywords:  myotonic dystrophy Type 1; senescence; senolytics; senomorphics
    DOI:  https://doi.org/10.1002/bies.202400216
  23. Mol Neurobiol. 2024 Dec 23.
      Accumulation of senescent neurons in the dorsal root ganglion (DRG) is an important tissue phenotype that causes age-related degeneration of peripheral sensory nerves. Senescent neurons are neurons with arrested cell cycle that have undergone cellular senescence but remain in the tissue and play various biological roles. To understand the accumulation of senescent neurons in the DRG during aging, we aimed to elucidate the mechanism that induces cellular senescence in DRG neurons and the role of senescent DRG neurons. We integrated multiple public transcriptome datasets for DRGs, which include cell bodies in neurons, and the sciatic nerve, which includes axons in neurons, using network medicine-based bioinformatics analysis. We thus inferred the molecular mechanisms involved in cellular senescence of DRG neurons, from molecular responses to senescence, in the DRG-sciatic nerve network. Network medicine-based bioinformatics analysis revealed that age-related Mapk3 decline leads to impaired cholesterol metabolism and biosynthetic function in axons, resulting in compensatory upregulation of Srebf1, a transcription factor involved in lipid and cholesterol metabolism. This in turn leads to CDKN2A-mediated cellular senescence. Furthermore, our analysis revealed that senescent DRG neurons develop a senescence phenotype characterized by activation of antigen-presenting cells via upregulation of Ctss as a hub gene. B cells were inferred as antigen-presenting cells activated by Ctss, and CD8-positive T cells were inferred as cells that receive antigen presentation from B cells.
    Keywords:  Aging; Bioinformatics; Cellular senescence; Dorsal root ganglion; Peripheral nerve; Transcriptome
    DOI:  https://doi.org/10.1007/s12035-024-04666-8
  24. Nat Aging. 2024 Dec 27.
      The emerging field of senolytics is centered on eliminating senescent cells to block their contribution to the progression of age-related diseases, including cancer, and to facilitate healthy aging. Enhancing the selectivity of senolytic treatments toward senescent cells stands to reduce the adverse effects associated with existing senolytic interventions. Taking advantage of lipofuscin accumulation in senescent cells, we describe here the development of a highly efficient senolytic platform consisting of a lipofuscin-binding domain scaffold, which can be conjugated with a senolytic drug via an ester bond. As a proof of concept, we present the generation of GL392, a senolytic compound that carries a dasatinib senolytic moiety. Encapsulation of the GL392 compound in a micelle nanocarrier (termed mGL392) allows for both in vitro and in vivo (in mice) selective elimination of senescent cells via targeted release of the senolytic agent with minimal systemic toxicity. Our findings suggest that this platform could be used to enhance targeting of senotherapeutics toward senescent cells.
    DOI:  https://doi.org/10.1038/s43587-024-00747-4
  25. Biochim Biophys Acta Mol Cell Biol Lipids. 2024 Dec 22. pii: S1388-1981(24)00141-0. [Epub ahead of print]1870(2): 159591
      Sphingolipids are crucial components of cell membranes and serve as important signaling molecules. Ceramide, as the central hub of sphingolipid metabolism, plays a significant role in various biological processes, including the cell cycle, apoptosis, and cellular aging. Alterations in sphingolipid metabolism are implicated in cellular aging, however, the specific sphingolipid components and intrinsic mechanisms that mediate this process remain largely uncharacterized. In this study, we established a targeted sphingolipidomics approach and employed LC-MS/MS to quantitatively analyze changes in ceramide levels during chronological aging and in sur2Δ strains, aiming to elucidate the role of ceramides in regulating chronological lifespan. Our study revealed that in Saccharomyces cerevisiae, the C4 hydroxylase Sur2 and its product, phytoceramide, increase during chronological aging. While the loss of SUR2 function leads to a near-complete loss of phytoceramides and an accumulation of dihydroceramides, resulting in a significant reduction of total ceramide content to about half of that in wild-type cells. This ceramide profile alteration impairs both mitochondrial morphology and function, ultimately shortening the chronological lifespan. The knockout of SIT4 restores mitochondrial morphology and function, and rescues the chronological lifespan of SUR2-deficient yeast. Our findings highlight the critical role of dihydroceramide and phytoceramide in chronological aging in yeast and suggest that an imbalance between these two metabolites may trigger downstream ceramide signaling pathways. These insights could help elucidate potential mechanisms through which ceramide imbalance contributes to disease development in higher organisms.
    Keywords:  Ceramide; Chronological lifespan; Sphingolipid metabolism; Sur2; Yeast
    DOI:  https://doi.org/10.1016/j.bbalip.2024.159591
  26. Diseases. 2024 Dec 04. pii: 317. [Epub ahead of print]12(12):
      Metabolic dysfunction-associated steatotic liver disease (MASLD) causes cellular senescence due to oxidative stress, endoplasmic reticulum stress, and ectopic fat deposition in the liver. Recently, dasatinib, an antitumor agent, and quercetin, a dietary supplement, were combined as a senolytic drug to eliminate senescent cells. Thus, this study aimed to examine the effects of dasatinib and quercetin administration on removing senescent cells and their therapeutic effects on MASLD in a medaka MASLD model. Dasatinib and quercetin were administered to a medaka MASLD model, which was fed a high-fat diet by dissolving them in aquarium water. The results revealed that senescent cells in the liver were increased in the HFD group but improved in the treatment group. Hematoxylin and eosin staining also showed that treatment improved fat deposition in hepatocytes. In addition, TGFβ1, a driver factor of fibrosis, was reduced in the treatment group. Dasatinib and quercetin eliminated senescent cells in MASLD, attenuated fat deposition, and suppressed fibrosis gene expression. The results indicate that dasatinib and quercetin as senolytic drugs are novel therapeutic agents that reduce MASLD.
    Keywords:  MASLD; NASH; medaka; senescence; senolytic drug
    DOI:  https://doi.org/10.3390/diseases12120317
  27. Sci Rep. 2024 Dec 28. 14(1): 30919
      Exposure to reactive oxygen species (ROS) can induce DNA-protein crosslinks (DPCs), unusually bulky DNA lesions that block replication and transcription and play a role in aging, cancer, cardiovascular disease, and neurodegenerative disorders. Repair of DPCs depends on the coordinated efforts of proteases and DNA repair enzymes to cleave the protein component of the lesion to smaller DNA-peptide crosslinks which can be processed by tyrosyl-DNA phosphodiesterases 1 and 2, nucleotide excision and homologous recombination repair pathways. DNA-dependent metalloprotease SPRTN plays a role in DPC repair, and SPRTN-deficient mice exhibit an accelerated aging phenotype and develop liver cancer early in life. We investigated the role of the SPRTN enzyme in the repair of DPCs produced by a free radical mechanism. Sprtn-deficient MEF cells treated with ionizing radiation had higher levels of total DPCs and exhibited greater sensitivity upon exposure to hydrogen peroxide and other crosslinking agents including cisplatin, phosphoramide mustard, and 1,2,3,4-diepoxybutane. Using a sensitive and accurate nanoLC-ESI+-MS/MS assay, we specifically measured the radical-induced crosslinking of thymidine in DNA crosslinking of thymidine in DNA to tyrosine in proteins (dT-Tyr) in the tissues of SPRTN hypomorphic (SprtnH/H) and wild type mice. Genomic DNA isolated from the tissues of SPRTN hypomorphic (SprtnH/H) mice exhibited higher levels of dT-Tyr in the liver, brain, heart, and kidney than wild-type animals. Overall, our results are consistent with the understanding that SPRTN has a role in maintaining genomic integrity upon exposure to ionizing radiation and endogenous reactive oxygen species.
    DOI:  https://doi.org/10.1038/s41598-024-81799-9
  28. Altern Ther Health Med. 2024 Dec 18. pii: AT11190. [Epub ahead of print]
       Background: Telomere length has been identified as a marker for biological aging and stressful body states. Mind-body interventions for stress reduction such as meditation, yoga, and pranayama have been previously tested to evaluate their efficacy in restricting telomere shortening.
    Primary Study Objective: In this study, the effect of Sudarshan Kriya Yoga (SKY) is investigated for its influence on telomere length.
    Methods: Isolating the genomic DNA from the blood, relative telomere length was found using a quantitative PCR method for the SKY intervention group and a control group. Telomere maintenance gene expression was assessed from a microarray gene expression dataset.
    Setting: Sri Sri Institute for Advanced Research, Bangalore.
    Participants: Employees, working at a corporate organization were the participants of this study. 11 individuals were enrolled in the intervention group while 5 were enrolled in the control group.
    Intervention: The integrated yoga-meditation practice, Sudarshan Kriya Yoga (SKY).
    Primary Outcome Measures: The relative telomere length and the expression of telomere maintenance genes from the genomic DNA isolated from the participants' blood samples.
    Results: Telomere length after SKY increased significantly compared to the baseline. However, in the controls, the corresponding change was insignificant. The telomere maintenance gene expression analysis reveals an intervention response conducive to telomere length extension at the molecular level.
    Conclusion: The extension of telomere length after SKY underscores its efficacy in stress reduction and improved health-span.
  29. Food Funct. 2024 Dec 24.
      Food-derived active peptides (FDAPs) are a class of peptides that exert antioxidant, anti-inflammatory, anti-aging and other effects. In recent years, active peptides from natural foods have been reported to improve skin photoaging, but their mechanisms have not been summarized to date. In this review, we focused on the preparation of FDAPs, their mechanisms of photoaging, and their function against photoaging through the gastrointestinal barrier. Furthermore, the latest progress on FDAPs in the prevention and treatment of skin photoaging via the gut-skin axis is summarized and discussed. FDAPs can be directly absorbed into the gastrointestinal tract and enter skin tissues to exert anti-photoaging effects; they can also regulate the gut microbiota, leading to changes in metabolites to ameliorate light-induced skin aging. Future work needs to focus on the delivery system and clinical validation of anti-photoaging peptides to provide solutions or suggestions for improving photoaging.
    DOI:  https://doi.org/10.1039/d4fo04202f
  30. Neurobiol Aging. 2024 Dec 15. pii: S0197-4580(24)00217-3. [Epub ahead of print]147 88-97
      Age-related cognitive decline presents a healthcare challenge. While age-related mechanisms are mainly studied in humans, animal models provide key insights. Despite evidence of sex-specific differences in aging and cognition, the impact of age on female rodent behaviour is underexplored. This study investigated age-related behavioural changes in female C57BL/6 mice over 8 months, alongside neurochemical markers amyloid, Tau, and T14, a novel peptide from acetylcholinesterase (AChE) that promotes cell growth/renewal. Behavioural assessments showed an age-dependent decline in nest-building ability and familiar odour discrimination from 10 months. Spatial learning declined at 10 and 13 months, while object recognition memory remained intact from 5 to 13 months of age. Neurochemical analyses revealed a decline in T14 and its receptor α7-AChR during postnatal development and adulthood. However, there was a disparity between AChE expression and its enzymatic activity. T14 levels correlated with phosphorylated tau, but not amyloid, and negatively with nest-building scores, suggesting a role of T14 in age-related behavioural changes. This study highlights early behavioural and molecular indicators of cognitive decline in middle-aged female mice.
    Keywords:  AChE; Alzheimer; Amyloid; Neurodegeneration; T14; Tau; α7-AChR
    DOI:  https://doi.org/10.1016/j.neurobiolaging.2024.12.003
  31. Int J Nanomedicine. 2024 ;19 13563-13578
       Purpose: Stem cell therapy is a promising approach for treating chronic diabetic wounds. However, its effectiveness is significantly limited by the high oxidative stress environment and persistent inflammation induced by diabetes. Strategies to overcome these challenges are essential to enhance the therapeutic potential of stem cell therapy.
    Methods: Cu5.4O ultrasmall nanoparticles (Cu5.4O-USNPs), known for their excellent reactive oxygen species (ROS) scavenging properties, were utilized to protect adipose-derived stem cells (ADSCs) from oxidative stress injury. In vitro experiments were conducted to evaluate the viability, paracrine activity, and anti-inflammatory capabilities of ADSCs loaded with Cu5.4O-USNPs under oxidative stress conditions. In vivo experiments in diabetic mice were performed to assess the therapeutic effects of Cu5.4O-USNP-loaded ADSCs on wound healing, including their impact on inflammation, collagen synthesis, angiogenesis, and wound closure.
    Results: ADSCs treated with Cu5.4O-USNPs showed significantly enhanced viability, paracrine activity, and anti-inflammatory properties under oxidative stress conditions in vitro. In diabetic mice, Cu5.4O-USNP-loaded ADSCs reduced inflammatory responses in wound tissues, promoted collagen synthesis and angiogenesis, and accelerated diabetic wound healing. These findings suggest that Cu5.4O-USNPs effectively mitigate the adverse effects of oxidative stress and inflammation, enhancing the therapeutic efficacy of ADSCs.
    Conclusion: This study presents a simple and effective approach to improve the therapeutic potential of stem cell therapy for diabetic wounds. By incorporating Cu5.4O-USNPs, the antioxidative and anti-inflammatory capabilities of ADSCs are significantly enhanced, offering a promising strategy for ROS-related tissue repair and chronic wound healing.
    Keywords:  ADSCs; Cu5.4O-USNPs; inflammatory environment; stem cell therapy
    DOI:  https://doi.org/10.2147/IJN.S487647
  32. Eur J Med Chem. 2024 Dec 17. pii: S0223-5234(24)01062-6. [Epub ahead of print]284 117180
      Autophagy is a lysosome-dependent cellular degradation pathway that responds to a variety of environmental and cellular stresses, which is defective in aging and age-related diseases, therefore, targeting autophagy with small-molecule activators has potential therapeutic benefits. In this study, we successfully completed the first total synthesis of Ivesinol, an identified antibacterial natural product, and efficiently constructed a library of its analogs. To measure the effect of Ivesinol analogs on autophagic activity, we performed cell imaging-based screening approach, and observed that several Ivesinol analogs exhibited potent autophagy-regulating activity. Specifically, the derivative B2 significantly activated autophagy activity in concentration- and time-dependent manners, and even outperformed the commonly used activator Torin1 in activating autophagy in MCF-7 cells at 0.5 μM. Bioinformatics analysis showed that B2 treatment significantly impacted ubiquitin mediated proteolysis and AMPK signaling pathway, with functionally related gene sets displaying strong correlations. Based on these findings, we proposed that B2 activates autophagy by mechanisms involved in downregulation of key HSP70 family members, activation of the UPR, and ultimately leading to autophagy. In conclusion, we suggest that B2 could be a promising and valuable autophagy activator with significant potential for further development.
    Keywords:  Autophagy activator; Ivesinol; Natural product; Total synthesis
    DOI:  https://doi.org/10.1016/j.ejmech.2024.117180
  33. ACS Synth Biol. 2024 Dec 25.
      Myeloid cells, including macrophages, neutrophils, dendritic cells, and myeloid-derived suppressor cells, play crucial roles in the innate immune system, contributing to immune defense, tissue homeostasis, and organ development. They have tremendous potential as therapeutic tools for diseases such as cancer and autoimmune disorders, but harnessing cell engineering strategies to enhance potency and expand applications is challenging. Recent advancements in stem cell research have made it possible to differentiate human embryonic stem cells and induce pluripotent stem cells into various cell types, including myeloid cells, offering a promising new approach to generate myeloid cells for cell therapy. In this review, we explore the latest techniques for the genetic engineering of myeloid cells, discussing both established and emerging methodologies. We examine the challenges faced in this field and the therapeutic potential of engineered myeloid cells. We also describe examples of engineered macrophages, neutrophils, and dendritic cells in various disease contexts. By providing a detailed overview of the current state and future directions, we aim to highlight progress and ongoing efforts toward harnessing the full therapeutic potential of genetically engineered myeloid cells.
    Keywords:  Chimeric Antigen Receptor; Dendritic Cells; Engineered Myeloid Cells; Macrophages; Neutrophils; Pluripotent Stem Cells
    DOI:  https://doi.org/10.1021/acssynbio.4c00589
  34. J Pain Res. 2024 ;17 4317-4329
       Introduction: Having a lower socioeconomic status (SES) is a predictor of age-related chronic conditions, including chronic low back pain (cLBP). We aimed to examine whether the pace of biological aging mediates the relationship between SES and cLBP outcomes - pain intensity, pain interference, and physical performance.
    Methods: We used the Dunedin Pace of Aging Calculated from the Epigenome (DunedinPACE) software to determine the pace of biological aging in adults ages 18 to 85 years with no cLBP (n = 74), low-impact pain (n = 56), and high-impact pain (n = 77).
    Results: The mean chronological age of the participants was 40.9 years (SD= 15.1); 107 (51.7%) were female, and 108 (52.2%) were Black. On average, the pace of biological aging was 5% faster [DunedinPACE = 1.05 (SD = 0.14)] in the sample (DunedinPACE value of 1 = normal pace of aging). Individuals with higher levels of education had a significantly slower pace of biological aging than those with lower education levels (F = 5.546, p = 0.001). After adjusting for sex and race, household income level significantly correlated with the pace of biological aging (r = -0.17, p = 0.02), pain intensity (r = -0.21, p = 0.003), pain interference (r = -0.21, p = 0.003), and physical performance (r = 0.20, p = 0.005). In mediation analyses adjusting for sex, race, and body mass index (BMI), the pace of biological aging mediates the relationship between household income (but not education) level and cLBP intensity, interference, as well as physical performance.
    Discussion: Results indicate that lower SES contributes to faster biological aging, possibly contributing to greater pain intensity and interference, as well as lower physical performance. Future interventions slowing the pace of biological aging may improve cLBP outcomes.
    Keywords:  DunedinPACE; chronic low back pain; epigenetic clock; health disparities; pace of biological aging; socioeconomic status
    DOI:  https://doi.org/10.2147/JPR.S481452
  35. Front Cell Neurosci. 2024 ;18 1471192
      The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has profoundly impacted global health, affecting not only the immediate morbidity and mortality rates but also long-term health outcomes across various populations. Although the acute effects of COVID-19 on the respiratory system have initially been the primary focus, it is increasingly evident that the virus can have significant impacts on multiple physiological systems, including the nervous and immune systems. The pandemic has highlighted the complex interplay between viral infection, immune aging, and brain health, that can potentially accelerate neuroimmune aging and contribute to the persistence of long COVID conditions. By inducing chronic inflammation, immunosenescence, and neuroinflammation, COVID-19 may exacerbate the processes of neuroimmune aging, leading to increased risks of cognitive decline, neurodegenerative diseases, and impaired immune function. Key factors include chronic immune dysregulation, oxidative stress, neuroinflammation, and the disruption of cellular processes. These overlapping mechanisms between aging and COVID-19 illustrate how the virus can induce and accelerate aging-related processes, leading to an increased risk of neurodegenerative diseases and other age-related conditions. This mini-review examines key features and possible mechanisms of COVID-19-induced neuroimmune aging that may contribute to the persistence and severity of long COVID. Understanding these interactions is crucial for developing effective interventions. Anti-inflammatory therapies, neuroprotective agents, immunomodulatory treatments, and lifestyle interventions all hold potential for mitigating the long-term effects of the virus. By addressing these challenges, we can improve health outcomes and quality of life for millions affected by the pandemic.
    Keywords:  COVID-19; brain aging; immunosenescence; inflammaging; long COVID; neuroinflammation; neurological disorders
    DOI:  https://doi.org/10.3389/fncel.2024.1471192
  36. Sci Rep. 2024 Dec 28. 14(1): 30924
      High glucose (HG) induced endothelial senescence is related to endothelial dysfunction and cardiovascular complications in diabetic patients. Humanin, a member of mitochondrial derived peptides (MDPs), is thought to contribute to aging-related cardiovascular protection. The goal of the study is to explore the pathogenesis of HG-induced endothelial senescence and potential anti-senescent effects of Humanin. Human umbilical vein endothelial cells (HUVECs) were exposed to glucose to induce senescence, determined by β-galactosidase staining and the expressions of p21, p53, and p16. A clinically relevant dose of HG (15 mM, HG) induced endothelial senescence after 72 h incubation without elevated apoptosis. HG-induced senescence was attributed to the induction of reactive oxygen species (ROS) caused by SIRT6 downregulation, as ROS inhibitor N-acetyl cysteine blocked HG-induced senescence, while inactivation of SIRT6 increased ROS levels and promoted senescence. Strikingly. pretreatment with [Gly14]-Humanin (HNG) antagonized the downregulation of SIRT6 in response to HG and alleviated ROS production and cell senescence. HG-induced reduction of SIRT6 results in ROS overproduction and endothelial senescence. Humanin protects against HG-induced endothelial senescence via SIRT6. This study provides new directions for biological products related to Humanin to be a potential candidate for the prevention of vascular aging in diabetes.
    Keywords:  Endothelial cells; Humanin; Reactive oxygen species; SIRT6; Senescence
    DOI:  https://doi.org/10.1038/s41598-024-81878-x