BiogerontologyPub Date : 2024-09-11DOI: 10.1007/s10522-024-10135-5
Kento Takaya, Kazuo Kishi
{"title":"Identification of a new human senescent skin cell marker ribonucleoside-diphosphate reductase subunit M2 B","authors":"Kento Takaya, Kazuo Kishi","doi":"10.1007/s10522-024-10135-5","DOIUrl":"https://doi.org/10.1007/s10522-024-10135-5","url":null,"abstract":"<p>In skin aging, it has been hypothesized that aging fibroblasts accumulate within the epidermal basal layer, dermis, and subcutaneous fat, causing abnormal tissue remodeling and extracellular matrix dysfunction, thereby inducing an aging-related secretory phenotype (SASP). A new treatment for skin aging involves the specific elimination of senescent skin cells, especially fibroblasts within the dermis and keratinocytes in the basal layer. This requires the identification of specific protein markers of senescent cells, such as ribonucleoside-diphosphate reductase subunit M2 B (RRM2B), which is upregulated in various malignancies in response to DNA stress damage. However, the behavior and role of RRM2B in skin aging remain unclear. Therefore, we examined whether RRM2B functions as a senescence marker using a human dermal fibroblast model of aging. In a model of cellular senescence induced by replicative aging and exposure to ionizing radiation or UVB, RRM2B was upregulated at the gene and protein levels. This was correlated with decreased uptake of the senescence-associated β-galactosidase activity and proliferation marker bromodeoxyuridine. <i>RRM2B</i> upregulation was concurrent with the increased expression of SASP factor genes. Furthermore, using fluorescence flow cytometry, RRM2B-positive cells were recovered more frequently in the aging cell population. In aging human skin, RRM2B was also found to be more abundant in the dermis and epidermal basal layer than other proteins. Therefore, RRM2B may serve as a clinical marker to identify senescent skin cells.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"58 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202115","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}
BiogerontologyPub Date : 2024-09-11DOI: 10.1007/s10522-024-10139-1
Chih-Lin Lee, Yu-Chiao Lin, Tsung-Han Kuo
{"title":"The impact of social partners: investigating mixed-strain housing effects on aging in female mice","authors":"Chih-Lin Lee, Yu-Chiao Lin, Tsung-Han Kuo","doi":"10.1007/s10522-024-10139-1","DOIUrl":"https://doi.org/10.1007/s10522-024-10139-1","url":null,"abstract":"<p>Aging is a multifaceted process characterized by the gradual decline of physiological functions and can be modulated by various internal and external factors. While social interactions have been shown to affect behaviors and physiology in different species, the impact of social partners on aging-related phenotypes and lifespan in mice remains understudied. To address this question, we investigated various aging-related traits and lifespan in two mouse strains, C57BL/6J and BALB/c, under two different housing conditions: mixed-strain and same-strain housing. Analyses using a Generalized Linear Model revealed significant differences between the two strains in several phenotypes, including metabolic, anxiety-like, and electrocardiographic traits. However, surprisingly, housing conditions did not significantly affect most of the examined parameters, including overall lifespan. Only 3 out of 25 traits—body weight change in a metabolic cage, running wheel activity, and survival days of a quartiles of mice with middle lifespans—were influenced by housing conditions in a strain-dependent manner. Together, our study suggested a minimal influence of co-housing with social partners from different genetic backgrounds on aging-related phenotypes. This result demonstrates the feasibility of mixed housing for mouse husbandry and, more importantly, provides valuable insights for future research on the social influences on the aging process in mice.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"47 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202116","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}
BiogerontologyPub Date : 2024-09-11DOI: 10.1007/s10522-024-10138-2
Daigo Okada
{"title":"The opposite aging effect to single cell transcriptome profile among cell subsets","authors":"Daigo Okada","doi":"10.1007/s10522-024-10138-2","DOIUrl":"https://doi.org/10.1007/s10522-024-10138-2","url":null,"abstract":"<p>Comparing transcriptome profiling between younger and older samples reveals genes related to aging and provides insight into the biological functions affected by aging. Recent research has identified sex, tissue, and cell type-specific age-related changes in gene expression. This study reports the overall picture of the opposite aging effect, in which aging increases gene expression in one cell subset and decreases it in another cell subset. Using the Tabula Muris Senis dataset, a large public single-cell RNA sequencing dataset from mice, we compared the effects of aging in different cell subsets. As a result, the opposite aging effect was observed widely in the genes, particularly enriched in genes related to ribosomal function and translation. The opposite aging effect was observed in the known aging-related genes. Furthermore, the opposite aging effect was observed in the transcriptome diversity quantified by the number of expressed genes and the Shannon entropy. This study highlights the importance of considering the cell subset when intervening with aging-related genes.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"179 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202118","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}
BiogerontologyPub Date : 2024-08-01Epub Date: 2024-05-15DOI: 10.1007/s10522-024-10105-x
Simon Okholm
{"title":"Geroscience: just another name or is there more to it?","authors":"Simon Okholm","doi":"10.1007/s10522-024-10105-x","DOIUrl":"10.1007/s10522-024-10105-x","url":null,"abstract":"<p><p>The widespread use of the name 'geroscience' in the science of aging is sometimes met with a wary attitude by biogerontologists other than its inventors. Here, we provide an overview of its origin and evolution to assess what exactly it is and to discuss its theoretical and biological relationship to earlier movements of anti-aging medicine and biogerontology more generally. Geroscience posits that targeting aging may offer a cost-effective approach to improve late-life health in humans, and because aging is malleable in model organisms and what regulates this is sufficiently understood, the time is ripe for moving forward to translational and clinical research. The geroscience agenda has rebranded imagery of past traditions, yet the claim that therapies for human aging are ready or within the imminent future is contestable and on brand with tradition, even if biogerontology has made great progress in the past decades.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"739-743"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921140","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}
{"title":"Sustained exposure to high glucose induces differential expression of cellular senescence markers in murine macrophages but impairs immunosurveillance response to senescent cells secretome.","authors":"Bhawna Diwan, Rahul Yadav, Rohit Goyal, Rohit Sharma","doi":"10.1007/s10522-024-10092-z","DOIUrl":"10.1007/s10522-024-10092-z","url":null,"abstract":"<p><p>The influence of chronic diseases on various facets of macrophage cellular senescence is poorly understood. This study evaluated the impact of chronic hyperglycemia on the induction of cellular senescence and subsequent immunosurveillance functions in RAW264.7 macrophages. Macrophages were cultured under normal glucose (NG; 5 mM), high glucose (HG; 20 mM), and very high glucose (VHG; 40 mM) conditions and assessed for markers of cellular senescence. Hyperglycemia induced strong upregulation of SA-β-gal activity, and loss of PCNA and Lamin B1 gene expression while markers of cell cycle arrest generally decreased. Non-significant changes in SASP-related proteins were observed while ROS levels slightly decreased and mitochondrial membrane potential increased. Protein concentration on the exosome membrane surface and their stability appeared to increase under hyperglycemic conditions. However, when macrophages were exposed to the secretory media (SM) of senescent preadipocytes, a dramatic increase in the levels of all inflammatory proteins was recorded especially in the VHG group that was also accompanied by upregulation of NF-κB and NLRP3 gene expression. SM treatment to hyperglycemic macrophages activated the TLR-2/Myd88 pathway but decreased the expression of scavenger receptors RAGE, CD36, and Olr-1 while CD44 and CXCL16 expression increased. On exposure to LPS, a strong upregulation in NO, ROS, and inflammatory cytokines was observed. Together, these results suggest that primary markers of cellular senescence are aberrantly expressed under chronic hyperglycemic conditions in macrophages with no significant SASP activation. Nonetheless, hyperglycemia strongly deregulates macrophage functions leading to impaired immunosurveillance of senescent cells and aggravation of inflamm-aging. This work provides novel insights into how hyperglycemia-induced dysfunctions can impact the potency of macrophages to manage senescent cell burden in aging tissues.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"627-647"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490349","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}
BiogerontologyPub Date : 2024-08-01Epub Date: 2024-03-28DOI: 10.1007/s10522-024-10100-2
Hye-Yeon Lee, Ji-Hyeon Lee, Jisun Baek, Kyung A Cho, Kyung-Jin Min
{"title":"Piperine improves the health span of Drosophila melanogaster with age- and sex-specific effect.","authors":"Hye-Yeon Lee, Ji-Hyeon Lee, Jisun Baek, Kyung A Cho, Kyung-Jin Min","doi":"10.1007/s10522-024-10100-2","DOIUrl":"10.1007/s10522-024-10100-2","url":null,"abstract":"<p><p>Piperine, a dietary phytochemical isolated from the Piper species, has been used as a natural medicine for pain, flu, and fever in ancient China and India. Although the health benefits of piperine have been widely studied, research on its effect on aging is limited. This study aimed to determine whether piperine has the potential to mitigate aging-related changes in the fruit fly (Drosophila melanogaster), which is an excellent model organism for studies on aging. The experiments were conducted using the newly eclosed or 30-day-old D. melanogaster wild-type strain Cantonized-white. Piperine was dissolved in 99% ethanol and added to the sucrose-yeast medium at a final concentration of 10, 35, 70, or 100 μM. The study examined the effects of piperine supplementation on the lifespan of D. melanogaster and other physiological functions, such as fecundity, feeding, lipid content, and resistance to environmental stress. Log-rank tests, Shapiro-Wilk test, F-test, t-test, or Wilcoxon rank sum test were used to analyze the data. Piperine failed to change the lifespan and body weight, but increased the fecundity and decreased the feeding rate in one-week-old flies. However, when piperine was fed to 30-day-old flies, it increased the lifespan of male flies and the fecundity and feeding rate of female flies. These results indicate that piperine can improve the health of aged flies. The findings suggest that piperine has age-dependent and sex-specific anti-aging effects in fruit flies.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"665-677"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317738","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}
BiogerontologyPub Date : 2024-08-01Epub Date: 2024-03-05DOI: 10.1007/s10522-024-10097-8
Hiskias Gerrit Keizer, R Brands, Ronald Sake Oosting, Willem Seinen
{"title":"A comprehensive model for the biochemistry of ageing, senescence and longevity.","authors":"Hiskias Gerrit Keizer, R Brands, Ronald Sake Oosting, Willem Seinen","doi":"10.1007/s10522-024-10097-8","DOIUrl":"10.1007/s10522-024-10097-8","url":null,"abstract":"<p><p>Various models for ageing, each focussing on different biochemical and/or cellular pathways have been proposed. This has resulted in a complex and non-coherent portrayal of ageing. Here, we describe a concise and comprehensive model for the biochemistry of ageing consisting of three interacting signalling hubs. These are the nuclear factor kappa B complex (NFκB), controlling the innate immune system, the mammalian target for rapamycin complex, controlling cell growth, and the integrated stress responses, controlling homeostasis. This model provides a framework for most other, more detailed, biochemical pathways involved in ageing, and explains why ageing involves chronic inflammation, cellular senescence, and vulnerability to environmental stress, while starting with the spontaneous formation of advanced glycation end products. The totality of data underlying this model suggest that the gradual inhibition of the AMPK-ISR probably determines the maximal lifespan. Based on this model, anti-ageing drugs in general, are expected to show hormetic dose response curves. This complicates the process of dose-optimization. Due to its specific mechanism of action, the anti-aging drug alkaline phosphatase is an exception to this rule, because it probably exhibits saturation kinetics.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"615-626"},"PeriodicalIF":4.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027302","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}
{"title":"Age and dietary restriction modulate mitochondrial quality in quadriceps femoris muscle of male mice.","authors":"Ting-Rui Zhang, Chun-Hsien Chiang, Tzu-Chieh Hsu, Chih-Yun Wang, Ching-Yi Chen","doi":"10.1007/s10522-023-10086-3","DOIUrl":"10.1007/s10522-023-10086-3","url":null,"abstract":"<p><p>Dietary restriction (DR) is a potential intervention for ameliorating ageing-related damages. Mitochondrial quality control is the key mechanism for regulating cellular functions in skeletal muscle. This study aimed to explore the effect of age and DR on the homeostasis of mitochondrial quality control in skeletal muscle. To study the effect of age on mitochondrial homeostasis, young (3 months old) male C57BL/6J mice were fed ad libitum (AL) until 7 (Young), 14 (Middle), and 19 months (Aged) of age. For the DR intervention, 60% of AL intake was given to the mice at 3 months of age until they reached 19 months of age (16 months). The quadriceps femoris muscle was collected for further analysis. Significant changes in the skeletal muscle were noticed during the transition between middle age and the elderly stages. An accumulation of collagen was observed in the muscle after middle age. Compared with the Middle muscle, Aged muscle displayed a greater expression of VDAC, and lower expressions of mitochondrial dynamic proteins and OXPHOS proteins. The DR intervention attenuated collagen content and elongated the sarcomere length in the skeletal muscle during ageing. In addition, DR adjusted the abnormalities in mitochondrial morphology in the Aged muscle. DR downregulated VDAC expression, but upregulated OPA1 and DRP1 expressions. Taken together, greater pathological changes were noticed in the skeletal muscle during ageing, especially in the transition between middle age and the elderly, whereas early-onset DR attenuated the muscular ageing via normalising partial functions of mitochondria.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"447-459"},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110739","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}
BiogerontologyPub Date : 2024-06-01Epub Date: 2024-03-04DOI: 10.1007/s10522-024-10096-9
Kento Takaya, Kazuo Kishi
{"title":"Regulation of ENPP5, a senescence-associated secretory phenotype factor, prevents skin aging.","authors":"Kento Takaya, Kazuo Kishi","doi":"10.1007/s10522-024-10096-9","DOIUrl":"10.1007/s10522-024-10096-9","url":null,"abstract":"<p><p>Aging negatively affects the appearance and texture of the skin owing to the accumulation of senescent fibroblasts within the dermis. Senescent cells undergo abnormal remodeling of collagen and the extracellular matrix through an inflammatory histolytic senescence-associated secretory phenotype (SASP). Therefore, suppression of SASP in senescent cells is essential for the development of effective skin anti-aging therapies. Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5), an extracellular signaling molecule, has been implicated in vascular aging and apoptosis; however, its role in SASP remains unclear. Therefore, this study aimed to investigate the role of ENPP5 in SASP and skin aging using molecular techniques. We investigated the effects of siRNA-mediated ENPP5 knockdown, human recombinant ENPP5 (rENPP5) treatment, and lentiviral overexpression of ENPP5 on SASP and aging in human skin fibroblasts. Additionally, we investigated the effect of siRNA-mediated ENPP5 knockdown on the skin of C57BL/6 mice. We found that ENPP5 was significantly expressed in replication-aged and otherwise DNA-damaged human skin fibroblasts and that treatment with human rENPP5 and lentiviral overexpression of ENPP5 promoted SASP and senescence. By contrast, siRNA-mediated knockdown of ENPP5 suppressed SASP and the expression of skin aging-related factors. Additionally, ENPP5 knockdown in mouse skin ameliorated the age-related reduction of subcutaneous adipose tissue, the panniculus carnosus muscle layer, and thinning of collagen fibers. Conclusively, these findings suggest that age-related changes may be prevented through the regulation of ENPP5 expression to suppress SASP in aging cells, contributing to the development of anti-aging treatments for the skin.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"529-542"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140020831","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}
BiogerontologyPub Date : 2024-06-01Epub Date: 2023-10-04DOI: 10.1007/s10522-023-10070-x
Xiaoyu Huang, Mao Chen, Ya Xiao, Fangyi Zhu, Liying Chen, Xiaoyu Tian, Li Hong
{"title":"The influence of biological sex in human skeletal muscle transcriptome during ageing.","authors":"Xiaoyu Huang, Mao Chen, Ya Xiao, Fangyi Zhu, Liying Chen, Xiaoyu Tian, Li Hong","doi":"10.1007/s10522-023-10070-x","DOIUrl":"10.1007/s10522-023-10070-x","url":null,"abstract":"<p><p>Sex is a crucial biological variable, and influence of biological sex on the change of gene expression in ageing skeletal muscle has not yet been fully revealed. In this study, the mRNA expression profiles were obtained from the Gene Expression Omnibus database. Key genes were identified by differential expression analysis and weighted gene co-expression network analysis. The gene set enrichment analysis software and Molecular Signatures Database were used for functional and enrichment analysis. A protein-protein interaction network was constructed using STRING and visualized in Cytoscape. The results were compared between female and male subgroups. Differentially expressed genes and enriched pathways in different sex subgroups shared only limited similarities. The pathways enriched in the female subgroup were more similar to the pathways enriched in the older groups without taking sex difference into consideration. The pathways enriched in the female subgroup were more similar to the pathways enriched in the older groups without taking sex difference into consideration. The muscle myosin filament pathways were downregulated in the both aged female and male samples whereas transforming growth factor beta pathway and extracellular matrix-related pathways were upregulated. With muscle ageing, the metabolism-related pathways, protein synthesis and degradation pathways, results of predicted immune cell infiltration, and gene cluster associated with slow-type myofibers drastically different between the female and male subgroups. This finding may indicate that changes in muscle type with ageing may differ between the sexes in vastus lateralis muscle.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"461-478"},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41095566","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}