Pub Date : 2024-11-01Epub Date: 2024-07-06DOI: 10.1007/s10522-024-10118-6
Shaojun Wang, Hong Yang
The intestinal barrier weakens and chronic gut inflammation occurs in old age, causing age-related illnesses. Recent research shows that low-molecular-weight heparin (LMWH), besides anticoagulation, also has anti-inflammatory and anti-apoptotic effects, protecting the intestinal barrier. This study aims to analyze the effect of LMWH on the intestinal barrier of old male rodents. This study assigned Sprague-Dawley male rats to four groups: young (3 months), young + LMWH, old (20 months), and old + LMWH. The LMWH groups received 1 mg/kg LMWH via subcutaneous injection for 7 days. Optical and transmission electron microscopy (TEM) were used to examine morphological changes in intestinal mucosa due to aging. Intestinal permeability was measured using fluorescein isothiocyanate (FITC)-dextran. ELISA kits were used to measure serum levels of IL-6 and IL-1β, while Quantitative RT-PCR detected their mRNA levels in intestinal tissues. Western blotting and immunohistochemistry (IHC) evaluated the tight junction (TJ) protein levels such as occludin, zonula occludens-1 (ZO-1), and claudin-2. Western blotting assessed the expression of the apoptosis marker cleaved caspase 3, while IHC was used to detect LGR5+ intestinal stem cells. The intestinal permeability of aged rats was significantly higher than that of young rats, indicating significant differences. With age, the protein levels of occludin and ZO-1 decreased significantly, while the level of claudin-2 increased significantly. Meanwhile, our study found that the levels of IL-1β and IL-6 increased significantly with age. LMWH intervention effectively alleviated age-related intestinal barrier dysfunction. In aged rats treated with LMWH, the expression of occludin and ZO-1 proteins in the intestine increased, while the expression of claudin-2 decreased. Furthermore, LMWH administration in aged rats resulted in a decrease in IL-1β and IL-6 levels. LMWH also reduced age-related cleaved caspase3 expression, but IHC showed no difference in LGR5+ intestinal stem cells between groups. Research suggests that LMWH could potentially be a favorable therapeutic choice for age-related diseases associated with intestinal barrier dysfunction, by protecting TJ proteins, reducing inflammation, and apoptosis.
{"title":"Low-molecular-weight heparin ameliorates intestinal barrier dysfunction in aged male rats via protection of tight junction proteins.","authors":"Shaojun Wang, Hong Yang","doi":"10.1007/s10522-024-10118-6","DOIUrl":"10.1007/s10522-024-10118-6","url":null,"abstract":"<p><p>The intestinal barrier weakens and chronic gut inflammation occurs in old age, causing age-related illnesses. Recent research shows that low-molecular-weight heparin (LMWH), besides anticoagulation, also has anti-inflammatory and anti-apoptotic effects, protecting the intestinal barrier. This study aims to analyze the effect of LMWH on the intestinal barrier of old male rodents. This study assigned Sprague-Dawley male rats to four groups: young (3 months), young + LMWH, old (20 months), and old + LMWH. The LMWH groups received 1 mg/kg LMWH via subcutaneous injection for 7 days. Optical and transmission electron microscopy (TEM) were used to examine morphological changes in intestinal mucosa due to aging. Intestinal permeability was measured using fluorescein isothiocyanate (FITC)-dextran. ELISA kits were used to measure serum levels of IL-6 and IL-1β, while Quantitative RT-PCR detected their mRNA levels in intestinal tissues. Western blotting and immunohistochemistry (IHC) evaluated the tight junction (TJ) protein levels such as occludin, zonula occludens-1 (ZO-1), and claudin-2. Western blotting assessed the expression of the apoptosis marker cleaved caspase 3, while IHC was used to detect LGR5+ intestinal stem cells. The intestinal permeability of aged rats was significantly higher than that of young rats, indicating significant differences. With age, the protein levels of occludin and ZO-1 decreased significantly, while the level of claudin-2 increased significantly. Meanwhile, our study found that the levels of IL-1β and IL-6 increased significantly with age. LMWH intervention effectively alleviated age-related intestinal barrier dysfunction. In aged rats treated with LMWH, the expression of occludin and ZO-1 proteins in the intestine increased, while the expression of claudin-2 decreased. Furthermore, LMWH administration in aged rats resulted in a decrease in IL-1β and IL-6 levels. LMWH also reduced age-related cleaved caspase3 expression, but IHC showed no difference in LGR5+ intestinal stem cells between groups. Research suggests that LMWH could potentially be a favorable therapeutic choice for age-related diseases associated with intestinal barrier dysfunction, by protecting TJ proteins, reducing inflammation, and apoptosis.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"1039-1051"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544484","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}
Pub Date : 2024-11-01Epub Date: 2024-08-21DOI: 10.1007/s10522-024-10131-9
Brecht Driesschaert, Lucas Mergan, Cristiano Lucci, Caroline Simon, Dulce Santos, Lies De Groef, Liesbet Temmerman
While the main role of phagocytic scavenger cells consists of the neutralization and elimination of pathogens, they also keep the body fluids clean by taking up and breaking down waste material. Since a build-up of waste is thought to contribute to the aging process, these cells become particularly pertinent in the research field of aging. Nevertheless, a direct link between their scavenging functions and the aging process has yet to be established. Integrative approaches involving various model organisms hold promise to elucidate this potential, but are lagging behind since the diversity and evolutionary relationship of these cells across animal species remain unclear. In this perspective, we review the current knowledge associating phagocytic scavenger cells with aging in vertebrate and invertebrate animals, as well as put forward important questions for further exploration. Additionally, we highlight future challenges and propose a constructive approach for tackling them.
{"title":"The role of phagocytic cells in aging: insights from vertebrate and invertebrate models.","authors":"Brecht Driesschaert, Lucas Mergan, Cristiano Lucci, Caroline Simon, Dulce Santos, Lies De Groef, Liesbet Temmerman","doi":"10.1007/s10522-024-10131-9","DOIUrl":"10.1007/s10522-024-10131-9","url":null,"abstract":"<p><p>While the main role of phagocytic scavenger cells consists of the neutralization and elimination of pathogens, they also keep the body fluids clean by taking up and breaking down waste material. Since a build-up of waste is thought to contribute to the aging process, these cells become particularly pertinent in the research field of aging. Nevertheless, a direct link between their scavenging functions and the aging process has yet to be established. Integrative approaches involving various model organisms hold promise to elucidate this potential, but are lagging behind since the diversity and evolutionary relationship of these cells across animal species remain unclear. In this perspective, we review the current knowledge associating phagocytic scavenger cells with aging in vertebrate and invertebrate animals, as well as put forward important questions for further exploration. Additionally, we highlight future challenges and propose a constructive approach for tackling them.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"1301-1314"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016249","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}
As one of the most vital organelles within biological cells, mitochondria hold an irreplaceable status and play crucial roles in various diseases. Research and therapies targeting mitochondria have achieved significant progress in numerous conditions. Throughout an organism's lifespan, mitochondrial dynamics persist continuously, and due to their inherent characteristics and various external factors, mitochondria are highly susceptible to damage. This susceptibility is particularly evident during aging, where the decline in biological function is closely intertwined with mitochondrial dysfunction. Despite being an ancient and enigmatic organelle, much remains unknown about mitochondria. Here, we will explore the past and present knowledge of mitochondria, providing a comprehensive review of their intrinsic properties and interactions with nuclear DNA, as well as the challenges and impacts they face during the aging process.
线粒体是生物细胞内最重要的细胞器之一,具有不可替代的地位,在各种疾病中发挥着至关重要的作用。针对线粒体的研究和疗法在多种疾病中取得了重大进展。在生物体的整个生命周期中,线粒体的动态变化持续存在,由于其固有的特性和各种外部因素,线粒体极易受到损伤。这种易损性在衰老过程中尤为明显,生物功能的衰退与线粒体功能障碍密切相关。尽管线粒体是一个古老而神秘的细胞器,但人们对它仍有许多未知。在这里,我们将探讨线粒体过去和现在的知识,全面回顾线粒体的内在特性、与核 DNA 的相互作用,以及线粒体在衰老过程中面临的挑战和影响。
{"title":"Mitochondria: fundamental characteristics, challenges, and impact on aging.","authors":"Runyu Liang, Luwen Zhu, Yongyin Huang, Jia Chen, Qiang Tang","doi":"10.1007/s10522-024-10132-8","DOIUrl":"10.1007/s10522-024-10132-8","url":null,"abstract":"<p><p>As one of the most vital organelles within biological cells, mitochondria hold an irreplaceable status and play crucial roles in various diseases. Research and therapies targeting mitochondria have achieved significant progress in numerous conditions. Throughout an organism's lifespan, mitochondrial dynamics persist continuously, and due to their inherent characteristics and various external factors, mitochondria are highly susceptible to damage. This susceptibility is particularly evident during aging, where the decline in biological function is closely intertwined with mitochondrial dysfunction. Despite being an ancient and enigmatic organelle, much remains unknown about mitochondria. Here, we will explore the past and present knowledge of mitochondria, providing a comprehensive review of their intrinsic properties and interactions with nuclear DNA, as well as the challenges and impacts they face during the aging process.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"923-941"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079061","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}
Pub Date : 2024-11-01Epub Date: 2024-07-22DOI: 10.1007/s10522-024-10123-9
A Golubev
According to the Gompertz law, the age-dependent change in the logarithm of mortality (life-table aging rate, LAR) is equal to the population-averaged age-independent biological aging rate (γ), and LAR would be constant if aging were the only cause of mortality increase. However, LAR is influenced by population exposures to the external hazards. If they were constant, according to the Gompertz-Makeham law (GML), LAR would be below γ at lower ages and asymptotically and monotonically approach γ with increasing age. Actually, LAR trajectories derived from data on mortality in different countries and historical periods feature systematic undulations. In the present investigation, mortality-vs.-age trajectories were modeled based on a generalized GML (gGML). Unlike the canonical GML terms, which are population-specific constants, the respective terms of the gGML are represented with some population-specific functions of age. Invariant in gGML are the modes of translation of these functions into the dependency of mortality on age: linear for population exposure to the irresistible external hazards or exponential for population-averaged ability to withstand the resistible external and internal hazards. Modeling suggests that, at earlier ages, LAR undulations are attributable to changes in population exposures to the former hazards. However, only their unrealistically high levels can produce the transient increase in LAR at about 65 to 90 years. This pervasive undulation of LAR-vs.-age trajectory is rather caused by an increment in γ. Reasons to regard gGML as a genuine natural law, which defines relations between mortality, aging and environment, are discussed.
根据贡珀茨定律,与年龄相关的死亡率对数变化(生命表老化率,LAR)等于与年龄无关的人口平均生物老化率(γ),如果老化是死亡率上升的唯一原因,则 LAR 将保持不变。然而,LAR 受人口暴露于外部危害的影响。如果它们保持不变,根据贡珀茨-马凯姆定律(GML),低年龄段的 LAR 将低于 γ,并随着年龄的增加而渐近和单调地接近 γ。实际上,根据不同国家和历史时期的死亡率数据得出的 LAR 轨迹具有系统性起伏的特点。本研究根据广义 GML(gGML)对死亡率-年龄轨迹进行建模。与典型的 GML 项(特定人口的常数)不同,gGML 的相应项用特定人口的年龄函数来表示。gGML 中不变的是这些函数转化为死亡率与年龄关系的模式:线性表示人口暴露于不可抗拒的外部危害的程度,指数表示人口平均抵御可抗拒的外部和内部危害的能力。建模表明,在较早的年龄段,LAR 的起伏是由于人口遭受前一种危害的程度发生了变化。然而,只有其不切实际的高水平才能产生 LAR 在 65 至 90 岁左右的瞬时增长。这种 LAR 随年龄变化的普遍起伏是由γ 的增加引起的。本文讨论了将 gGML 视为真正的自然法则的理由,它定义了死亡率、衰老和环境之间的关系。
{"title":"Invariances in relations between aging, exposure to external hazards, and mortality reflected in life table aging rate (LAR) patterns examined through the lens of generalized Gompertz-Makeham law.","authors":"A Golubev","doi":"10.1007/s10522-024-10123-9","DOIUrl":"10.1007/s10522-024-10123-9","url":null,"abstract":"<p><p>According to the Gompertz law, the age-dependent change in the logarithm of mortality (life-table aging rate, LAR) is equal to the population-averaged age-independent biological aging rate (γ), and LAR would be constant if aging were the only cause of mortality increase. However, LAR is influenced by population exposures to the external hazards. If they were constant, according to the Gompertz-Makeham law (GML), LAR would be below γ at lower ages and asymptotically and monotonically approach γ with increasing age. Actually, LAR trajectories derived from data on mortality in different countries and historical periods feature systematic undulations. In the present investigation, mortality-vs.-age trajectories were modeled based on a generalized GML (gGML). Unlike the canonical GML terms, which are population-specific constants, the respective terms of the gGML are represented with some population-specific functions of age. Invariant in gGML are the modes of translation of these functions into the dependency of mortality on age: linear for population exposure to the irresistible external hazards or exponential for population-averaged ability to withstand the resistible external and internal hazards. Modeling suggests that, at earlier ages, LAR undulations are attributable to changes in population exposures to the former hazards. However, only their unrealistically high levels can produce the transient increase in LAR at about 65 to 90 years. This pervasive undulation of LAR-vs.-age trajectory is rather caused by an increment in γ. Reasons to regard gGML as a genuine natural law, which defines relations between mortality, aging and environment, are discussed.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"1079-1096"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733486","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":"Correction: Chronic trans fatty acid consumption shortens lifespan in male Drosophila melanogaster on a high-sugar and high-fat diet.","authors":"Qianhua Yuan, Mengliu Luo, Yutong Xie, Wanhan Song, Ya Wang, Dazhang Deng, Shuyan Chen, Honghui Guo","doi":"10.1007/s10522-024-10116-8","DOIUrl":"10.1007/s10522-024-10116-8","url":null,"abstract":"","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"1299"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465986","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}
Pub Date : 2024-11-01Epub Date: 2024-07-06DOI: 10.1007/s10522-024-10117-7
Pynskhem Bok Swer, Babiangshisha Kharbuli, Donkupar Syiem, Ramesh Sharma
BRG1 (Brahma-related gene 1) is a member of the SWI/SNF (switch/sucrose nonfermentable) chromatin remodeling complex which utilizes the energy from ATP hydrolysis for its activity. In addition to its role of regulating the expression of a vast array of genes, BRG1 mediates DNA repair upon genotoxic stress and regulates senescence. During organismal ageing, there is accumulation of unrepaired/unrepairable DNA damage due to progressive breakdown of the DNA repair machinery. The present study investigates the expression level of BRG1 as a function of age in the liver of 5- and 21-month-old female mice. It also explores the impact of dietary restriction on BRG1 expression in the old (21-month) mice. Salient findings of the study are: Real-time PCR and Western blot analyses reveal that BRG1 levels are higher in 5-month-old mice but decrease significantly with age. Dietary restriction increases BRG1 expression in the 21-month-old mice, nearly restoring it to the level observed in the younger group. Similar expression patterns are observed for DNA damage response genes ATM (Ataxia Telangiectasia Mutated) and ATR (Ataxia Telangiectasia and Rad3-related) with the advancement in age and which appears to be modulated by dietary restriction. BRG1 transcriptionally regulates ATM as a function of age and dietary restriction. These results suggest that BRG1, ATM and ATR are downregulated as mice age, and dietary restriction can restore their expression. This implies that dietary restriction may play a crucial role in regulating BRG1 and related gene expression, potentially maintaining liver repair and metabolic processes as mice age.
BRG1(梵天相关基因 1)是 SWI/SNF(开关/蔗糖不发酵)染色质重塑复合体的成员,它利用 ATP 水解产生的能量进行活动。除了调节大量基因的表达外,BRG1 还能在基因毒性应激时介导 DNA 修复,并调节衰老。在机体衰老过程中,由于 DNA 修复机制逐渐崩溃,未修复/可修复的 DNA 损伤不断积累。本研究调查了 5 个月大和 21 个月大雌性小鼠肝脏中 BRG1 的表达水平与年龄的关系。研究还探讨了饮食限制对老龄(21 个月)小鼠 BRG1 表达的影响。研究的主要发现有实时 PCR 和 Western 印迹分析表明,5 个月大小鼠的 BRG1 水平较高,但随着年龄的增长会显著降低。饮食限制会增加 21 个月大小鼠的 BRG1 表达量,几乎恢复到较小鼠组的水平。随着年龄的增长,DNA损伤反应基因ATM(Ataxia Telangiectasia Mutated)和ATR(Ataxia Telangiectasia and Rad3-related)也出现了类似的表达模式,并且似乎受到饮食限制的调节。BRG1对ATM的转录调节与年龄和饮食限制有关。这些结果表明,随着小鼠年龄的增长,BRG1、ATM 和 ATR 的表达会降低,而饮食限制可以恢复它们的表达。这意味着饮食限制可能在调节BRG1及相关基因表达方面起着至关重要的作用,有可能随着小鼠年龄的增长而维持肝脏修复和代谢过程。
{"title":"Age-related decline in the expression of BRG1, ATM and ATR are partially reversed by dietary restriction in the livers of female mice.","authors":"Pynskhem Bok Swer, Babiangshisha Kharbuli, Donkupar Syiem, Ramesh Sharma","doi":"10.1007/s10522-024-10117-7","DOIUrl":"10.1007/s10522-024-10117-7","url":null,"abstract":"<p><p>BRG1 (Brahma-related gene 1) is a member of the SWI/SNF (switch/sucrose nonfermentable) chromatin remodeling complex which utilizes the energy from ATP hydrolysis for its activity. In addition to its role of regulating the expression of a vast array of genes, BRG1 mediates DNA repair upon genotoxic stress and regulates senescence. During organismal ageing, there is accumulation of unrepaired/unrepairable DNA damage due to progressive breakdown of the DNA repair machinery. The present study investigates the expression level of BRG1 as a function of age in the liver of 5- and 21-month-old female mice. It also explores the impact of dietary restriction on BRG1 expression in the old (21-month) mice. Salient findings of the study are: Real-time PCR and Western blot analyses reveal that BRG1 levels are higher in 5-month-old mice but decrease significantly with age. Dietary restriction increases BRG1 expression in the 21-month-old mice, nearly restoring it to the level observed in the younger group. Similar expression patterns are observed for DNA damage response genes ATM (Ataxia Telangiectasia Mutated) and ATR (Ataxia Telangiectasia and Rad3-related) with the advancement in age and which appears to be modulated by dietary restriction. BRG1 transcriptionally regulates ATM as a function of age and dietary restriction. These results suggest that BRG1, ATM and ATR are downregulated as mice age, and dietary restriction can restore their expression. This implies that dietary restriction may play a crucial role in regulating BRG1 and related gene expression, potentially maintaining liver repair and metabolic processes as mice age.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"1025-1037"},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544483","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}
Isotschimgine (ITG) is a bornane-type monoterpenoid derivative naturally occurring in genus Ferula plants and propolis. Its effects on aging and the underlying mechanisms are not yet well understood. This study employed Caenorhabditis elegans (C. elegans) as a model organism to evaluate the potential of ITG in extending lifespan, enhancing healthspan, and promoting neuroprotection, while exploring the underlying mechanisms involved. The results showed that ITG extended the lifespan and healthspan of C. elegans, significantly enhanced stress resistance and detoxification functions. Studies on mutants and qPCR data indicated that ITG-mediated lifespan extension was modulated by the insulin/IGF-1 signaling pathway and nuclear hormone receptors. Furthermore, ITG markedly increased stress-responsive genes, including daf-16 and its downstream genes sod-3 and hsp-16.2, as well as NHR downstream detoxification-related genes cyp35a1, cyp35b3, cyp35c1, gst-4, pgp-3 and pgp-13. Additionally, ITG alleviated β-amyloid-induced paralysis and behavioral dysfunction in transgenic C. elegans strains. The neuroprotective efficacy of ITG was weakened by RNAi knockdown of nuclear hormone receptors daf-12 and nhr-8. Overall, our study identifies ITG as a potential compound for promoting longevity and neuroprotection, mediated through nuclear hormone receptors.
{"title":"Isotschimgine promotes lifespan, healthspan and neuroprotection of Caenorhabditis elegans via the activation of nuclear hormone receptors.","authors":"Hang Shi, Xiaoyan Gao, Jing Yu, Lijun Zhang, Bingbing Fan, Ying Liu, Xinyi Wang, Shengjie Fan, Cheng Huang","doi":"10.1007/s10522-024-10142-6","DOIUrl":"https://doi.org/10.1007/s10522-024-10142-6","url":null,"abstract":"<p><p>Isotschimgine (ITG) is a bornane-type monoterpenoid derivative naturally occurring in genus Ferula plants and propolis. Its effects on aging and the underlying mechanisms are not yet well understood. This study employed Caenorhabditis elegans (C. elegans) as a model organism to evaluate the potential of ITG in extending lifespan, enhancing healthspan, and promoting neuroprotection, while exploring the underlying mechanisms involved. The results showed that ITG extended the lifespan and healthspan of C. elegans, significantly enhanced stress resistance and detoxification functions. Studies on mutants and qPCR data indicated that ITG-mediated lifespan extension was modulated by the insulin/IGF-1 signaling pathway and nuclear hormone receptors. Furthermore, ITG markedly increased stress-responsive genes, including daf-16 and its downstream genes sod-3 and hsp-16.2, as well as NHR downstream detoxification-related genes cyp35a1, cyp35b3, cyp35c1, gst-4, pgp-3 and pgp-13. Additionally, ITG alleviated β-amyloid-induced paralysis and behavioral dysfunction in transgenic C. elegans strains. The neuroprotective efficacy of ITG was weakened by RNAi knockdown of nuclear hormone receptors daf-12 and nhr-8. Overall, our study identifies ITG as a potential compound for promoting longevity and neuroprotection, mediated through nuclear hormone receptors.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 1","pages":"2"},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543427","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}
Pub Date : 2024-10-29DOI: 10.1007/s10522-024-10143-5
Mark T Mc Auley
Ageing is generally regarded as a non-adaptive by-product of evolution. Based on this premise three classic evolutionary theories of ageing have been proposed. These theories have dominated the literature for several decades. Despite their individual nuances, the common thread which unites them is that they posit that ageing results from a decline in the intensity of natural selection with chronological age. Empirical evidence has been identified which supports each theory. However, a consensus remains to be fully established as to which theory best accounts for the evolution of ageing. A consequence of this uncertainty are counter arguments which advocate for alternative theoretical frameworks, such as those which propose an adaptive origin for ageing, senescence, or death. Given this backdrop, this review has several aims. Firstly, to briefly discuss the classic evolutionary theories. Secondly, to evaluate how evolutionary forces beyond a monotonic decrease in natural selection can affect the evolution of ageing. Thirdly, to examine alternatives to the classic theories. Finally, to introduce a pluralistic interpretation of the evolution of ageing. The basis of this pluralistic theoretical framework is the recognition that certain evolutionary ideas will be more appropriate depending on the organism, its ecological context, and its life history.
{"title":"The evolution of ageing: classic theories and emerging ideas.","authors":"Mark T Mc Auley","doi":"10.1007/s10522-024-10143-5","DOIUrl":"10.1007/s10522-024-10143-5","url":null,"abstract":"<p><p>Ageing is generally regarded as a non-adaptive by-product of evolution. Based on this premise three classic evolutionary theories of ageing have been proposed. These theories have dominated the literature for several decades. Despite their individual nuances, the common thread which unites them is that they posit that ageing results from a decline in the intensity of natural selection with chronological age. Empirical evidence has been identified which supports each theory. However, a consensus remains to be fully established as to which theory best accounts for the evolution of ageing. A consequence of this uncertainty are counter arguments which advocate for alternative theoretical frameworks, such as those which propose an adaptive origin for ageing, senescence, or death. Given this backdrop, this review has several aims. Firstly, to briefly discuss the classic evolutionary theories. Secondly, to evaluate how evolutionary forces beyond a monotonic decrease in natural selection can affect the evolution of ageing. Thirdly, to examine alternatives to the classic theories. Finally, to introduce a pluralistic interpretation of the evolution of ageing. The basis of this pluralistic theoretical framework is the recognition that certain evolutionary ideas will be more appropriate depending on the organism, its ecological context, and its life history.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 1","pages":"6"},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543428","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}
Pub Date : 2024-10-29DOI: 10.1007/s10522-024-10144-4
Emma Kordek, Amaya Yip, Alicia Horton, Hope Sohn, Nicholas Strasser, Maya Makhtin, John Hatle
Finding interventions to break the trade-off between reproduction and lifespan can provide insight into physiological limitations of animals. Effects of dietary protein quality on the trade-off are currently unclear, but clarity could lead to better designed diets that match animal needs. Dietary amino acid blends matching yolk proteins support reproduction and extend lifespan in fruit flies. To test if this is conserved across species, we matched dietary amino acids to vitellogenin to test reproduction and lifespan in adult females of the lubber grasshopper. Specifically, we compared varying degrees of protein quality by manipulating dietary essential amino acids. We identified a high-quality protein diet (amino acids matched to vitellogenin, or reproductive needs) that increased reproduction and matched lifespan in comparison to diets that differed only in the ratios of essential amino acids (i.e., were isocaloric and isonitrogenous). All these diets had longer lifespan but lower reproductive output than fully fed controls. In a separate experiment, full reproduction was possible on the high-quality artificial diet when offered at a 78% higher protein quantity and with a larger lettuce supplement (~ 17% of ad libitum). Additionally, we observed that as dietary protein quality was decreased (i.e., diets were less matched to vitellogenin), reproduction was reduced, and lifespan was extended in the more extreme scenarios. Taken together, these results indicate that the balance of dietary essential amino acids plays an important role in the lifespan and reproduction trade-off, while more work needs to be conducted to find the optimal diet mix for this species.
{"title":"High-quality dietary protein (essential amino acids matched to reproductive needs) partially breaks the lifespan and reproduction trade-off in lubber grasshoppers.","authors":"Emma Kordek, Amaya Yip, Alicia Horton, Hope Sohn, Nicholas Strasser, Maya Makhtin, John Hatle","doi":"10.1007/s10522-024-10144-4","DOIUrl":"https://doi.org/10.1007/s10522-024-10144-4","url":null,"abstract":"<p><p>Finding interventions to break the trade-off between reproduction and lifespan can provide insight into physiological limitations of animals. Effects of dietary protein quality on the trade-off are currently unclear, but clarity could lead to better designed diets that match animal needs. Dietary amino acid blends matching yolk proteins support reproduction and extend lifespan in fruit flies. To test if this is conserved across species, we matched dietary amino acids to vitellogenin to test reproduction and lifespan in adult females of the lubber grasshopper. Specifically, we compared varying degrees of protein quality by manipulating dietary essential amino acids. We identified a high-quality protein diet (amino acids matched to vitellogenin, or reproductive needs) that increased reproduction and matched lifespan in comparison to diets that differed only in the ratios of essential amino acids (i.e., were isocaloric and isonitrogenous). All these diets had longer lifespan but lower reproductive output than fully fed controls. In a separate experiment, full reproduction was possible on the high-quality artificial diet when offered at a 78% higher protein quantity and with a larger lettuce supplement (~ 17% of ad libitum). Additionally, we observed that as dietary protein quality was decreased (i.e., diets were less matched to vitellogenin), reproduction was reduced, and lifespan was extended in the more extreme scenarios. Taken together, these results indicate that the balance of dietary essential amino acids plays an important role in the lifespan and reproduction trade-off, while more work needs to be conducted to find the optimal diet mix for this species.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 1","pages":"4"},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543426","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}
Pub Date : 2024-10-29DOI: 10.1007/s10522-024-10147-1
Abdur-Rehman Munir, Saad Ilyas Baig, Muhammad Asif Razzaq, Fatima Rauf, Yasir Ali, Syed Muhammad Abdullah Azam
The iron-sulfur domain (CISD) proteins of CDGSH are classified into three classes: CISD1, CISD2, and CISD3. During premature ageing, mutations that affect these proteins, namely their binding sites, could result in reduced protein production and an inability to preserve cellular integrity. Consequently, this leads to the development of conditions such as diabetes. Notably, CISD3 plays a crucial role in the management of age-related disorders such as Wolfram syndrome, which is often referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Computational analyses have predicted that CISD3 regulates the redox state, safeguards the endoplasmic reticulum and mitochondria, and maintains intracellular calcium levels. CISD3, a member of a recently discovered gene family associated with the CDGSH iron protein apoptotic compensatory response, fulfils a crucial function in mitigating the effects of accelerated ageing. The compound "(-)-(2S)-7,4'-Dihydroxyflavanone" has been discovered by computational drug design as a possible activator of CISD3. It shows potential therapeutic benefits in ameliorating metabolic dysfunction and enhancing glucose regulation. The ligand binds to the binding pocket of the CISD3 protein, increasing the stability of the protein and enhancing its functionality. The current research investigates the binding processes of the molecule in various structures and its anticipated effects on these tissues, therefore providing valuable insights into the mitigation of age-related diabetes and metabolic dysfunction. The projected tripling of the worldwide population of individuals aged 50 and above by 2050 necessitates the urgent development of immunoinformatics-based approaches, including pharmaceutical therapies that target CISD3, to prevent age-related pathologies. The stimulation of CISD3, namely by compounds such as "(-)-(2S)-7,4'-Dihydroxyflavanone", has the potential to counteract telomere shortening and improve metabolic pathways.
{"title":"A novel (-)-(2S)-7,4'-dihydroxyflavanone compound for treating age-related diabetes mellitus through immunoinformatics-guided activation of CISD3.","authors":"Abdur-Rehman Munir, Saad Ilyas Baig, Muhammad Asif Razzaq, Fatima Rauf, Yasir Ali, Syed Muhammad Abdullah Azam","doi":"10.1007/s10522-024-10147-1","DOIUrl":"https://doi.org/10.1007/s10522-024-10147-1","url":null,"abstract":"<p><p>The iron-sulfur domain (CISD) proteins of CDGSH are classified into three classes: CISD1, CISD2, and CISD3. During premature ageing, mutations that affect these proteins, namely their binding sites, could result in reduced protein production and an inability to preserve cellular integrity. Consequently, this leads to the development of conditions such as diabetes. Notably, CISD3 plays a crucial role in the management of age-related disorders such as Wolfram syndrome, which is often referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Computational analyses have predicted that CISD3 regulates the redox state, safeguards the endoplasmic reticulum and mitochondria, and maintains intracellular calcium levels. CISD3, a member of a recently discovered gene family associated with the CDGSH iron protein apoptotic compensatory response, fulfils a crucial function in mitigating the effects of accelerated ageing. The compound \"(-)-(2S)-7,4'-Dihydroxyflavanone\" has been discovered by computational drug design as a possible activator of CISD3. It shows potential therapeutic benefits in ameliorating metabolic dysfunction and enhancing glucose regulation. The ligand binds to the binding pocket of the CISD3 protein, increasing the stability of the protein and enhancing its functionality. The current research investigates the binding processes of the molecule in various structures and its anticipated effects on these tissues, therefore providing valuable insights into the mitigation of age-related diabetes and metabolic dysfunction. The projected tripling of the worldwide population of individuals aged 50 and above by 2050 necessitates the urgent development of immunoinformatics-based approaches, including pharmaceutical therapies that target CISD3, to prevent age-related pathologies. The stimulation of CISD3, namely by compounds such as \"(-)-(2S)-7,4'-Dihydroxyflavanone\", has the potential to counteract telomere shortening and improve metabolic pathways.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 1","pages":"5"},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543424","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}