Biogerontology最新文献

Inhibitory immune checkpoints suppress the surveillance of senescent cells promoting their accumulation with aging and in age-related diseases. 抑制性免疫检查点会抑制对衰老细胞的监控，从而促进衰老细胞的积累，并引发与年龄相关的疾病。

IF 4.4 4区医学

Biogerontology Pub Date : 2024-10-01 Epub Date: 2024-07-01 DOI: 10.1007/s10522-024-10114-w

Antero Salminen

{"title":"Inhibitory immune checkpoints suppress the surveillance of senescent cells promoting their accumulation with aging and in age-related diseases.","authors":"Antero Salminen","doi":"10.1007/s10522-024-10114-w","DOIUrl":"10.1007/s10522-024-10114-w","url":null,"abstract":"The accumulation of pro-inflammatory senescent cells within tissues is a common hallmark of the aging process and many age-related diseases. This modification has been called the senescence-associated secretory phenotype (SASP) and observed in cultured cells and in cells isolated from aged tissues. Currently, there is a debate whether the accumulation of senescent cells within tissues should be attributed to increased generation of senescent cells or to a defect in their elimination from aging tissues. Emerging studies have revealed that senescent cells display an increased expression of several inhibitory immune checkpoint ligands, especially those of the programmed cell death protein-1 (PD-1) ligand-1 (PD-L1) proteins. It is known that the PD-L1 ligands, especially those of cancer cells, target the PD-1 receptor of cytotoxic CD8+ T and natural killer (NK) cells disturbing their functions, e.g., evoking a decline in their cytotoxic activity and promoting their exhaustion and even apoptosis. An increase in the level of the PD-L1 protein in senescent cells was able to suppress their immune surveillance and inhibit their elimination by cytotoxic CD8+ T and NK cells. Senescent cells are known to express ligands for several inhibitory immune checkpoint receptors, i.e., PD-1, LILRB4, NKG2A, TIM-3, and SIRPα receptors. Here, I will briefly describe those pathways and examine whether these inhibitory checkpoints could be involved in the immune evasion of senescent cells with aging and age-related diseases. It seems plausible that an enhanced inhibitory checkpoint signaling can prevent the elimination of senescent cells from tissues and thus promote the aging process.","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Compensation effect of mortality is a challenge to substantial lifespan extension of humans. 死亡率的补偿效应是人类大幅延长寿命所面临的挑战。

IF 4.4 4区医学

Biogerontology Pub Date : 2024-10-01 Epub Date: 2024-05-29 DOI: 10.1007/s10522-024-10111-z

Natalia S Gavrilova, Leonid A Gavrilov

{"title":"Compensation effect of mortality is a challenge to substantial lifespan extension of humans.","authors":"Natalia S Gavrilova, Leonid A Gavrilov","doi":"10.1007/s10522-024-10111-z","DOIUrl":"10.1007/s10522-024-10111-z","url":null,"abstract":"Despite frequent claims regarding radical extensions of human lifespan in the near future, many pragmatic scientists caution against excessive and baseless optimism on this front. In this study, we examine the compensation effect of mortality (CEM) as a potential challenge to substantial lifespan extension. The CEM is an empirical mortality regularity, often depicted as relative mortality convergence at advanced ages. Analysis of mortality data from 44 human populations, available in the Human Mortality Database, demonstrated that CEM can be represented as a continuous decline in relative mortality variation (assessed through the coefficient of variation and the standard deviation of the logarithm of mortality) with age, reaching a minimum corresponding to the species-specific lifespan. Through this method, the species-specific lifespan is determined to be 96-97 years, closely aligning with estimates derived from correlations between Gompertz parameters (95-98 years). Importantly, this representation of CEM can be achieved non-parametrically, eliminating the need for estimating Gompertz parameters. CEM is a challenge to lifespan extension, because it suggests that the true aging rate in humans (based on loss of vital elements, e.g., functional cells) remains stable at approximately 1% per year in the majority of human populations and is not affected by environmental or familial longevity factors. Given this rate of functional cell loss, one might anticipate that the total pool of functional cells could be entirely depleted by the age of 115-120 years creating physiological limit to human lifespan. Mortality pattern of supercentenarians (110 + years) aligns with this prediction.","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intracellular cytokines in peritoneal leukocytes relate to lifespan in aging and long-lived female mice. 腹膜白细胞内细胞因子与衰老和长寿雌性小鼠的寿命有关。

IF 4.4 4区医学

Biogerontology Pub Date : 2024-10-01 Epub Date: 2024-05-15 DOI: 10.1007/s10522-024-10110-0

Irene Martínez de Toda, Judith Félix, Estefanía Díaz-Del Cerro, Mónica De la Fuente

{"title":"Intracellular cytokines in peritoneal leukocytes relate to lifespan in aging and long-lived female mice.","authors":"Irene Martínez de Toda, Judith Félix, Estefanía Díaz-Del Cerro, Mónica De la Fuente","doi":"10.1007/s10522-024-10110-0","DOIUrl":"10.1007/s10522-024-10110-0","url":null,"abstract":"Peritoneal immune cell function is a reliable indicator of aging and longevity in mice and inflammaging is associated with a shorter lifespan. Nevertheless, it is unknown if the content of cytokines in these immune cells is linked to individual differences in lifespan. Therefore, this work aimed to investigate different peritoneal leukocyte populations and their content in intracellular pro-inflammatory (TNF and IL-6) and anti-inflammatory (IL-10) cytokines by flow cytometry in adult (10 months-old, n = 8) and old (18 months-old, n = 20) female Swiss/ICR mice. In addition, old mice were monitored longitudinally throughout their aging process, and the same markers were analyzed at the very old (24 months-old, n = 8) and long-lived (30 months-old, n = 4) ages. The longitudinal follow-up allowed us to relate the investigated parameters to individual lifespans. The results show that long-lived female mice exhibit an adult-like profile in most parameters investigated but also display specific immune adaptations, such as increased CD4+ and CD8+ T cells containing the pro-inflammatory TNF cytokine and CD4+ T cells and macrophages containing the anti-inflammatory cytokine IL-10. These adaptations may underlie their exceptional longevity. In addition, a negative correlation was obtained between the percentage of cytotoxic T cells, KLRG-1/CD4, large peritoneal macrophages, and the percentage of CD4+ T cells containing IL-6 and macrophages containing IL-10 in old age and lifespan, whereas a positive correlation was found between the CD4/CD8 ratio and the longevity of the animals at the same age. These results highlight the crucial role of peritoneal leukocytes in inflammaging and longevity.","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The influence of sex-specific factors on biological transformations and health outcomes in aging processes. 老龄化过程中性别特异性因素对生物转化和健康结果的影响。

IF 4.4 4区医学

Biogerontology Pub Date : 2024-10-01 Epub Date: 2024-07-13 DOI: 10.1007/s10522-024-10121-x

Yongyin Huang, Hongyu Li, Runyu Liang, Jia Chen, Qiang Tang

引用次数: 0

Restricting the level of the proteins essential for the regulation of the initiation step of replication extends the chronological lifespan and reproductive potential in budding yeast. 限制对复制起始步骤的调控至关重要的蛋白质水平，可延长芽殖酵母的正常寿命和繁殖潜力。

IF 4.4 4区医学

Biogerontology Pub Date : 2024-10-01 Epub Date: 2024-06-06 DOI: 10.1007/s10522-024-10113-x

Karolina Stępień, Tuguldur Enkhbaatar, Monika Kula-Maximenko, Łukasz Jurczyk, Adrianna Skoneczna, Mateusz Mołoń

{"title":"Restricting the level of the proteins essential for the regulation of the initiation step of replication extends the chronological lifespan and reproductive potential in budding yeast.","authors":"Karolina Stępień, Tuguldur Enkhbaatar, Monika Kula-Maximenko, Łukasz Jurczyk, Adrianna Skoneczna, Mateusz Mołoń","doi":"10.1007/s10522-024-10113-x","DOIUrl":"10.1007/s10522-024-10113-x","url":null,"abstract":"Aging is defined as a progressive decline in physiological integrity, leading to impaired biological function, including fertility, and rising vulnerability to death. Disorders of DNA replication often lead to replication stress and are identified as factors influencing the aging rate. In this study, we aimed to reveal how the cells that lost strict control of the formation of crucial for replication initiation a pre-initiation complex impact the cells' physiology and aging. As strains with the lower pre-IC control (lowPICC) we used, Saccharomyces cerevisiae heterozygous strains having only one functional copy of genes, encoding essential replication proteins such as Cdc6, Dbf4, Sld3, Sld7, Sld2, and Mcm10. The lowPICC strains exhibited a significant reduction in the respective genes' mRNA levels, causing cell cycle aberrations and doubling time extensions. Additionally, the reduced expression of the lowPICC genes led to an aberrant DNA damage response, affected cellular and mitochondrial DNA content, extended the lifespan of post-mitotic cells, and increased the yeast's reproductive potential. Importantly, we also demonstrated a strong negative correlation between the content of cellular macromolecules (RNA, proteins, lipids, polysaccharides) and aging. The data presented here will likely contribute to the future development of therapies for treating various human diseases.","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of the relationship between age-related erythrocyte dysfunction and fatigue. 分析与年龄有关的红细胞功能障碍和疲劳之间的关系。

IF 4.4 4区医学

Biogerontology Pub Date : 2024-10-01 Epub Date: 2024-05-07 DOI: 10.1007/s10522-024-10106-w

Yuichiro Ogata, Takaaki Yamada, Masahiro Fujimura, Toshio Igarashi, Seiji Hasegawa

{"title":"Analysis of the relationship between age-related erythrocyte dysfunction and fatigue.","authors":"Yuichiro Ogata, Takaaki Yamada, Masahiro Fujimura, Toshio Igarashi, Seiji Hasegawa","doi":"10.1007/s10522-024-10106-w","DOIUrl":"10.1007/s10522-024-10106-w","url":null,"abstract":"With the declining birth rates and aging societies in developed countries, the average age of the working population is increasing. Older people tend to get tired more easily, so prevention of fatigue is important to improve the quality of life for older workers. This study aimed to assess the mechanism of fatigue in older people, especially focused on relation between dysfunction of erythrocyte and fatigue. Total power (TP), which is the value of autonomic nerve activity, was measured as a value of fatigue and significantly decreased in workers with aging. As properties of senescent erythrocytes, the erythrocyte sedimentation rate and damaged erythrocytes population increased with aging and correlated with TP. These results suggested that the accumulation of damaged erythrocytes contributes to fatigue. Recent studies revealed that senescence-associated secretory phenotype (SASP), a phenomenon in which senescent cells secrete a variety of cytokines, affected hematopoiesis in bone marrow. We analyzed the effects of SASP factors on erythropoiesis and found that Interleukin -1α (IL-1α) suppressed erythrocyte differentiation of hematopoietic stem cells in vitro. We also showed that IL-1α levels in human blood and saliva increase with aging, suggesting the possibility that IL-1α level in saliva can be used to predict the decline in hematopoietic function.","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The potential longevity-promoting hypoxic-hypercapnic environment as a measure for radioprotection. 作为放射防护措施的潜在长寿促进缺氧-高二氧化碳浓度环境。

IF 4.4 4区医学

Biogerontology Pub Date : 2024-10-01 Epub Date: 2024-08-20 DOI: 10.1007/s10522-024-10129-3

Elroei David, Marina Wolfson, Khachik K Muradian, Vadim E Fraifeld

引用次数: 0

Network pharmacology-based approach to investigate the molecular targets and molecular mechanisms of Rosmarinus officinalis L. for treating aging-related disorders. 基于网络药理学的方法，研究迷迭香治疗衰老相关疾病的分子靶点和分子机制。

IF 4.4 4区医学

Biogerontology Pub Date : 2024-10-01 Epub Date: 2024-07-17 DOI: 10.1007/s10522-024-10122-w

Amisha Bisht, Disha Tewari, Sanjay Kumar, Subhash Chandra

{"title":"Network pharmacology-based approach to investigate the molecular targets and molecular mechanisms of Rosmarinus officinalis L. for treating aging-related disorders.","authors":"Amisha Bisht, Disha Tewari, Sanjay Kumar, Subhash Chandra","doi":"10.1007/s10522-024-10122-w","DOIUrl":"10.1007/s10522-024-10122-w","url":null,"abstract":"Aging, a natural biological process, presents challenges in maintaining physiological well-being and is associated with increased vulnerability to diseases. Addressing aging mechanisms is crucial for developing effective preventive and therapeutic strategies against age-related ailments. Rosmarinus officinalis L. is a medicinal herb widely used in traditional medicine, containing diverse bioactive compounds that have been studied for their antioxidant and anti-inflammatory properties, which are associated with potential health benefits. Using network pharmacology, this study investigates the anti-aging function and underlying mechanisms of R. officinalis. Through network pharmacology analysis, the top 10 hub genes were identified, including TNF, CTNNB1, JUN, MTOR, SIRT1, and others associated with the anti-aging effects. This analysis revealed a comprehensive network of interactions, providing a holistic perspective on the multi-target mechanism underlying Rosemary's anti-aging properties. GO and KEGG pathway enrichment analysis revealed the relevant biological processes, molecular functions, and cellular components involved in treating aging-related conditions. KEGG pathway analysis shows that anti-aging targets of R. officinalis involved endocrine resistance, pathways in cancer, and relaxin signaling pathways, among others, indicating multifaceted mechanisms. Genes like MAPK1, MMP9, and JUN emerged as significant players. These findings enhance our understanding of R. officinalis's potential in mitigating aging-related disorders through multi-target effects on various biological processes and pathways. Such approaches may reduce the risk of failure in single-target and symptom-based drug discovery and therapy.","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of mTOR prevents glucotoxicity-mediated increase of SA-beta-gal, p16^INK4a, and insulin hypersecretion, without restoring electrical features of mouse pancreatic islets. 抑制 mTOR 可防止葡萄糖毒性介导的 SA-beta-gal、p16INK4a 和胰岛素分泌过多的增加，但不会恢复小鼠胰岛的电特性。

IF 4.4 4区医学

Biogerontology Pub Date : 2024-10-01 Epub Date: 2024-05-15 DOI: 10.1007/s10522-024-10107-9

Tereso J Guzmán, Nina Klöpper, Carmen M Gurrola-Díaz, Martina Düfer

{"title":"Inhibition of mTOR prevents glucotoxicity-mediated increase of SA-beta-gal, p16INK4a, and insulin hypersecretion, without restoring electrical features of mouse pancreatic islets.","authors":"Tereso J Guzmán, Nina Klöpper, Carmen M Gurrola-Díaz, Martina Düfer","doi":"10.1007/s10522-024-10107-9","DOIUrl":"10.1007/s10522-024-10107-9","url":null,"abstract":"An over-activation of the mechanistic target of rapamycin (mTOR) pathway promotes senescence and age-related diseases like type 2 diabetes. Besides, the regenerative potential of pancreatic islets deteriorates with aging. Nevertheless, the role of mTOR on senescence promoted by metabolic stress in islet cells as well as its relevance for electrophysiological aspects is not yet known. Here, we investigated whether parameters suggested to be indicative for senescence are induced in vitro in mouse islet cells by glucotoxicity and if mTOR inhibition plays a protective role against this. Islet cells exhibit a significant increase (~ 76%) in senescence-associated beta-galactosidase (SA-beta-gal) activity after exposure to glucotoxicity for 72 h. Glucotoxicity does not markedly influence p16INK4a protein within 72 h, but p16INK4a levels increase significantly after a 7-days incubation period. mTOR inhibition with a low rapamycin concentration (1 nM) entirely prevents the glucotoxicity-mediated increase of SA-beta-gal and p16INK4a. At the functional level, reactive oxygen species, calcium homeostasis, and electrical activity are disturbed by glucotoxicity, and rapamycin fails to prevent this. In contrast, rapamycin significantly attenuates the insulin hypersecretion promoted by glucotoxicity by modifying the mRNA levels of Vamp2 and Snap25 genes, related to insulin exocytosis. Our data indicate an influence of glucotoxicity on pancreatic islet-cell senescence and a reduction of the senescence markers by mTOR inhibition, which is relevant to preserve the regenerative potential of the islets. Decreasing the influence of mTOR on islet cells exposed to glucotoxicity attenuates insulin hypersecretion, but is not sufficient to prevent electrophysiological disturbances, indicating the involvement of mTOR-independent mechanisms.","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing the human health and lifespan: a targeted strategy emphasizing statins. 提高人类健康水平和寿命：强调他汀类药物的针对性战略。

IF 4.4 4区医学

Biogerontology Pub Date : 2024-10-01 Epub Date: 2024-05-29 DOI: 10.1007/s10522-024-10112-y

Edward Calabrese, Peter Pressman

{"title":"Enhancing the human health and lifespan: a targeted strategy emphasizing statins.","authors":"Edward Calabrese, Peter Pressman","doi":"10.1007/s10522-024-10112-y","DOIUrl":"10.1007/s10522-024-10112-y","url":null,"abstract":"There has been substantial research interest in finding activities/agents that slow the onset and reduce the severity of numerous age-related diseases/conditions. This assessment indicates that the most studied agent intended to promote health in human population investigations for a broad spectrum of diseases are the statins, with large-scale epidemiological studies addressing numerous health endpoints. The key findings are that statin treatment consistently reduces the occurrence and attenuates the course of numerous non-communicable and contagious pathologies and numerous types of cancer with high mortality rates by about 20-50%. That one agent could affect such a broad based and consistently positive trends in epidemiological studies is unexpected and impressive, along with consistent cell and animal model research. Underlying mechanisms have been proposed that significantly contribute to the spectrum of salutary effects of statins, especially the capacity to activate Nrf2 showing hormetic dose responses in multiple organs and cell types, due to its bioavailability and broad tissue distribution. The widespread use of statins, which has the capacity to enhance human health span, should be considered for experimental exploration as a novel public health strategy that includes practical approaches for reduction of the most common adverse effects of this class of drugs including myalgia/myopathy and transaminitis.","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0