{"title":"Analyzing the causal role of blood cells in aging: a Mendelian randomization study.","authors":"Jingjing Zhang, Xin Zhang, Boan Xiao, Jiecai Ouyang, Peng Wang, Xiaobin Peng","doi":"10.1007/s10522-024-10148-0","DOIUrl":"10.1007/s10522-024-10148-0","url":null,"abstract":"<p><p>Blood cells are crucial components of the human body, closely linked to the aging process. This study aims to explore the causal relationship between 91 blood cell phenotypes and aging through Mendelian randomization (MR) analysis. Exposure data from genome-wide association studies (GWAS) was extracted from the GWAS of blood cell perturbation phenotypes in 2,600 European individuals. Initial analysis utilized GWAS data related to aging from the GWAS Catalog database GCST90014288, with inverse-variance weighting as the primary method for causal analysis. Sensitivity analyses included Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. For significant associations, replication and meta-analysis were conducted using independent aging GWAS data from GCST90014300. Initial analysis revealed that environmental peroxide-impacted red blood cells and ciprofloxacin-impacted reticulocytes accelerated aging. Additionally, elevated neutrophil levels were found to accelerate aging, while LiCl-impacted neutrophils reduced aging risk. Replication and meta-analysis showed consistent results: ciprofloxacin-impacted reticulocytes and elevated neutrophil levels increased the risk of aging, while LiCl-impacted neutrophils reduced the risk. RBCs showed no significant impact on aging progression. Sensitivity analyses confirmed the robustness and reliability of these positive findings. Our study provides evidence of a causal relationship between three blood cell disturbance phenotypes and human aging.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567675","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 : 2024-11-01Epub Date: 2024-08-20DOI: 10.1007/s10522-024-10127-5
Xue Wang, Huan Liu, Mingwei Yue, Jinsong Wang, Chunmei Zhang, Lizheng Qin, Songlin Wang, Lei Hu
{"title":"Dietary nitrate maintains intestinal epithelia homeostasis in aged mice.","authors":"Xue Wang, Huan Liu, Mingwei Yue, Jinsong Wang, Chunmei Zhang, Lizheng Qin, Songlin Wang, Lei Hu","doi":"10.1007/s10522-024-10127-5","DOIUrl":"10.1007/s10522-024-10127-5","url":null,"abstract":"<p><p>The intestinal tract, which is the primary site of digestion and absorption of nutrients, is one of the most vulnerable organs during aging. Dietary nitrate, which is mainly derived from the diet and absorbed in the intestinal tract, is a key messenger that connecting oral and general health. However, whether dietary nitrate regulates intestinal tract homeostasis remains unclear. Our data revealed that the serum and salivary nitrate levels decreased during mice aging. The functional proteins of the epithelial barrier (E-cadherin, Claudin-1 and Zonula Occludens-1) in the colon tissues decreased during the aging process. Long-term nitrate supplement in drinking water restored the serum and salivary nitrate levels and increased the functional proteins expression of the colon epithelial barrier. Dietary nitrates increase the relative abundance of some intestinal probiotics, particularly those associated with the production of short-chain fatty acids, such as Blautia, Alloprevotella, Butyricicoccus, and Ruminococcaceae, while promoting the butyric acid production in the colon. Moreover, the expression of Sialin (encoded by Slc17a5), which is a nitrate transporter, increased in the colon epithelial cells by nitrate supplementation. The epithelial cell-conditional Slc17a5-knockout mutant mice (K14-cre; Slc17a5<sup>fl/fl</sup>) revealed that the functional proteins expression of the colon epithelial barrier and the proliferation of PCNA-positive intestinal epithelial cells in the colon crypts was significantly decreased compared with those of the K14-cre; Slc17a5<sup>fl/+</sup> mice. Taken together, our findings suggested that nitrate supplementations were associated with the increased expression of colonic epithelial barriers-related proteins and the increased Sialin expression. Nitrate may serve as a potential therapeutic approach in maintaining aged colonic homeostasis.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003554","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}
{"title":"The impact of mosaic loss of the Y chromosome (mLOY) in men of advanced age.","authors":"Farid Abou Abdallah, Christine Abdel Massih, Charbel Attieh, Alain Chebly","doi":"10.1007/s10522-024-10133-7","DOIUrl":"10.1007/s10522-024-10133-7","url":null,"abstract":"<p><p>The Y chromosome has long been considered to be a \"genetic wasteland\" harboring only few genes essentially involved in male sex development and spermatogenesis. However, the discovery of mosaic loss of the Y chromosome (mLOY) in older men has led to revisiting of the potential impact of the Y chromosome on health and the pathophysiological processes of multiple diseases such as cancer, Alzheimer's disease and cardiovascular disease. Hence, developing more sensitive techniques for the detection of mLOY has become an emergent concern. In this article, we present a comprehensive review of the literature regarding mLOY. Additionally, we discuss the emerging discoveries concerning mLOY as well as the underlying mechanisms promoting disease in men of advanced age.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118914","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 : 2024-11-01Epub Date: 2024-07-13DOI: 10.1007/s10522-024-10120-y
Virginia Boccardi, Luigi Cari, Patrizia Bastiani, Michela Scamosci, Roberta Cecchetti, Giuseppe Nocentini, Patrizia Mecocci
{"title":"Aberrant telomeric structures and serum markers of telomere dysfunction in healthy aging: a preliminary study.","authors":"Virginia Boccardi, Luigi Cari, Patrizia Bastiani, Michela Scamosci, Roberta Cecchetti, Giuseppe Nocentini, Patrizia Mecocci","doi":"10.1007/s10522-024-10120-y","DOIUrl":"10.1007/s10522-024-10120-y","url":null,"abstract":"<p><p>Telomeres undergo a progressive shortening process as individuals age, and it has been proposed that severely shortened and dysfunctional telomeres play a role in the aging process and the onset of age-related diseases in human beings. An emerging body of evidence indicates that the shortening of telomeres in cultured human cells is also influenced by other replication defects occurring within telomeric repeats. These abnormalities can be detected on metaphase chromosomes. Recent studies have also identified a set of serological markers for telomere dysfunction and DNA damage (elongation factor 1α [EF-1α], stathmin, and N-acetyl-glucosaminidase). With this study, the correlation between telomere abnormalities (by FISH) and these biomarkers as measured in blood serum (by ELISA) from a cohort of 22 healthy subjects at different ages (range 26-101 years) was analyzed. A strong positive correlation between aging and the presence of aberrant telomere structures, sister telomere loss (STL), and sister telomere chromatid fusions (STCF) was detected. When serum markers of telomere dysfunction were correlated with telomere abnormalities, we found that stathmin correlated with total aberrant telomeres structures (r = 0.431, p = 0.0453) and STCF (r = 0.533, p = 0.0107). These findings suggest that serum stathmin can be considered an easy-to-get marker of telomere dysfunction and may serve as valuable indicators of aging.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603266","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 : 2024-11-01Epub Date: 2024-07-17DOI: 10.1007/s10522-024-10119-5
Ajay Kumar Danga, Sukhleen Kour, Anita Kumari, Pramod C Rath
{"title":"The long noncoding RNA (LINC-RBE) expression in testicular cells is associated with aging of the rat.","authors":"Ajay Kumar Danga, Sukhleen Kour, Anita Kumari, Pramod C Rath","doi":"10.1007/s10522-024-10119-5","DOIUrl":"10.1007/s10522-024-10119-5","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) are important regulatory biomolecules responsible for many cellular processes. The aging of mammals is manifested by a slow and gradual decline of physiological functions after adulthood, progressively resulting in age-related diseases. Testis comprises different cell-types with defined functions for producing haploid gametes and androgens in males, contributing gene-pool to the next generation with genetic variations to species for evolutionary advantage. The LINC-RBE (long intergenic noncoding-rat brain expressed) RNA showed highest expression in the Leydig cells, responsible for steroidogenesis and production of testosterone; higher expression in primary spermatocytes (pachytene cells), responsible for generation of haploid gametes and high expression in Sertoli cells, the nursing cells of the testes. Testes of immature (4-weeks), adult (16- and 44-weeks), and nearly-old (70-weeks) rats showed low, high, and again low levels of expression, respectively. This along with the nuclear-cytoplasmic localization of LINC-RBE RNA showed age-related expression and function. Thus, expression of LINC-RBE is involved in the molecular physiology of testes, especially Leydig cells, primary spermatocytes, and Sertoli cells. The decline in its expression correlates with diminishing reproductive function of the testes during aging of the rat.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625872","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 : 2024-11-01Epub Date: 2024-09-06DOI: 10.1007/s10522-024-10134-6
Lloyd A Demetrius, Anand Sahasranaman, Martin Ziehe
{"title":"Directionality theory and mortality patterns across the primate lineage.","authors":"Lloyd A Demetrius, Anand Sahasranaman, Martin Ziehe","doi":"10.1007/s10522-024-10134-6","DOIUrl":"10.1007/s10522-024-10134-6","url":null,"abstract":"<p><p>Empirical studies of aging in primates show that local selective forces rather than phylogenetic history determine the exceptional nature of human longevity (Bronikowski et al., Science 331:1325-1328, 2011). This article proposes an evolutionary rationale for this pattern of primate mortality by invoking the parameter, Life-Table Entropy, a measure of the uncertainty in the life span of a randomly chosen newborn. Life-table entropy is positively correlated with maximal life span, that is, the mean life span of a species living under favourable conditions.The logic which underlies the exceptional nature of human longevity derives from the terrestrial life-history of humans - a singularity within the primate lineage; and the concomitant ecological constraints-the hunter-gatherer, agricultural, and industrial modes of subsistence, that have defined human evolutionary history. The effect of these ecological constraints on the evolution of life span is encoded in the Entropic Principle of Longevity: life-table entropy increases in equilibrium species, populations evolving in environments with stable, renewable resources; and decreases in opportunistic species, populations subject to fluctuating resource endowments.The Entropic Principle of Longevity is a derivative of Directionality Theory, an analytic study of the evolutionary process of variation and selection based on Evolutionary Entropy, a statistical measure of the uncertainty in the age of the mother of a randomly chosen newborn. Evolutionary entropy is the organizing concept of The Entropic Principle of Evolution: Evolutionary Entropy increases in equilibrium species and decreases in opportunistic species.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139214","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}
{"title":"Brown adipose tissue: a potential target for aging interventions and healthy longevity.","authors":"Hongde Li, Junli Li, Chengxiang Song, Haoran Yang, Qiang Luo, Mao Chen","doi":"10.1007/s10522-024-10137-3","DOIUrl":"10.1007/s10522-024-10137-3","url":null,"abstract":"<p><p>Brown Adipose Tissue (BAT) is a type of fat tissue that can generate heat and plays an important role in regulating body temperature and energy metabolism. Enhancing BAT activity through medication, exercise and other means has become a potential effective method for treating metabolic disorders. Recently, there has been increasing evidence suggesting a link between BAT and aging. As humans age, the volume and activity of BAT decrease, which may contribute to the development of age-related diseases. Multiple organelles signaling pathways have been reported to be involved in the aging process associated with BAT. Therefore, we aimed to review the evidence related to the association between aging process and BAT decreasing, analyze the potential of BAT as a predictive marker for age-related diseases, and explore potential therapeutic strategies targeting BAT for aging interventions and healthy longevity.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387610","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 : 2024-11-01Epub Date: 2024-08-28DOI: 10.1007/s10522-024-10130-w
Saad Ilyas Baig, Maria Naseer, Abdur-Rehman Munir, Yasir Ali, Muhammad Asif Razzaq
{"title":"Immunoinformatic-based drug design utilizing hesperetin to target CISD2 activation for liver aging in humans.","authors":"Saad Ilyas Baig, Maria Naseer, Abdur-Rehman Munir, Yasir Ali, Muhammad Asif Razzaq","doi":"10.1007/s10522-024-10130-w","DOIUrl":"10.1007/s10522-024-10130-w","url":null,"abstract":"<p><p>The CISD protein family, consisting of CISD1, CISD2, and CISD3, encodes proteins that feature CDGSH iron-sulfur domains crucial for cellular functions and share a common 2Fe-2S domain. CISD2, which is pivotal in cells, regulates intracellular calcium levels, maintains the endoplasmic reticulum and mitochondrial function, and is associated with longevity and overall health, with exercise stimulating CISD2 production. However, CISD2 expression decreases with age, impacting age-related processes. According to in silico docking, HST is a CISD2 activator that affects metabolic dysfunction and age-related illnesses by affecting metabolic pathways. This study investigated the ability of CISD2 and HST to reduce age-related ailments, with a particular emphasis on liver aging. CISD2 deficiency has a major effect on the function of cells, as it undermines the integrity of the ER, mitochondria, and calcium homeostasis. It also increases susceptibility to oxidative stress and metabolic dysregulation, which is linked to Wolfram syndrome and exacerbates age-related illnesses and metabolic disorders. By shielding cells from stress, CISD2 extends the life of cells and maintains liver health as people age. Its protective effecfts on the liver during aging are further enhanced by its control of translation factors such as Nrf2 and IL-6. This work paves the way for future investigations and clinical applications by examining the structural and functional properties of CISD2 and the interaction between CISD2 and HST. This highlights the therapeutic potential of these findings in promoting healthy livers in humans and battling age-related illnesses.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079060","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 : 2024-11-01Epub Date: 2024-09-26DOI: 10.1007/s10522-024-10141-7
Huimin Zheng, Tiantian Li, Ziyun Hu, Qi Zheng, Junsong Wang
{"title":"The potential of flavonoids to mitigate cellular senescence in cardiovascular disease.","authors":"Huimin Zheng, Tiantian Li, Ziyun Hu, Qi Zheng, Junsong Wang","doi":"10.1007/s10522-024-10141-7","DOIUrl":"10.1007/s10522-024-10141-7","url":null,"abstract":"<p><p>Aging is one of the most significant factors affecting cardiovascular health, with cellular senescence being a central hallmark. Senescent cells (SCs) secrete a specific set of signaling molecules known as the senescence-associated secretory phenotype (SASP). The SASP has a remarkable impact on age-associated diseases, particularly cardiovascular diseases (CVD). Targeting SCs through anti-aging therapies represents a novel strategy to effectively retard senescence and attenuate disease progression. Accumulating evidence demonstrates that the flavonoids, widely presented in fruits and vegetables worldwide, can delay or treat CVD via selectively eliminating SCs (senolytics) and modulating SASPs (senomorphics). Nevertheless, only sporadic research has illustrated the application of flavonoids in targeting SCs for CVD, which requires further exploration. This review recapitulates the hallmarks and key molecular mechanisms involved in cellular senescence, then summarizes senescence of different types of cardiac cells and describes the mechanisms by which cellular senescence affects CVD development. The discussion culminates with the potential use of flavonoids via exerting their biological effects on cellular senescence to reduce CVD incidence. This summary will provide valuable insights for cardiovascular drug design, development and clinical applications leveraging flavonoids.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340635","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 : 2024-11-01Epub Date: 2024-07-24DOI: 10.1007/s10522-024-10124-8
Debarati Chattopadhyay, Susan Mary Philip, Grace Prabhakar, Madappa Machamada Bheemaiah
{"title":"Influence of α-lipoic acid on longevity and stress resistance in Drosophila melanogaster fed with a high-fat diet.","authors":"Debarati Chattopadhyay, Susan Mary Philip, Grace Prabhakar, Madappa Machamada Bheemaiah","doi":"10.1007/s10522-024-10124-8","DOIUrl":"10.1007/s10522-024-10124-8","url":null,"abstract":"<p><p>Consumption of a high-fat diet is accompanied by the risks of obesity and early onset of age-associated complications for which dietary interventions are imperative to combat. α-lipoic acid has been shown to hinder diet-induced obesity and induce lifespan-extending efficacy in model organisms. In this study, α-lipoic acid was investigated for its efficacy in improving lifespan and stress resistance in the Canton-S strain of Drosophila melanogaster fed with a high-fat diet. Furthermore, as mating status significantly impacts survival in fruit flies, flies were reared in two experimental groups-group one, in which males and females were bred together, and group two, in which males and females were bred separately. In group one, α-lipoic acid improved the mean lifespan, reduced the fecundity of females, and reduced the mean body weight of flies at a dose range of 2-2.5 mM, respectively. In group two, α-lipoic acid improved the mean lifespan, reduced the fecundity of females, and reduced the mean body weight of flies at a dose range of 1-2.5 mM, respectively. Improved climbing efficiency was observed with α-lipoic acid at the dose range of 1.5-2.5 mM in flies of group one and 1-2.5 mM in flies of group two, respectively. Administration of α-lipoic acid improved resistance to oxidative stress in only female flies of group one at 2.5 mM, whereas in group two, both male and female flies exhibited enhanced resistance to oxidative stress with α-lipoic acid at a dose range of 2-2.5 mM, respectively. Male and female flies of only group one showed improved resistance to heat shock stress with α-lipoic acid at a dose range of 2-2.5 mM. Only female flies of group two exhibited a slight improvement in recovery time following cold shock with α-lipoic acid only at 2.5 mM. No significant change in resistance to starvation stress was observed with any dose of α-lipoic acid in either group of flies. To summarize, data from this study suggested a probable dose and gender-dependent efficacy of α-lipoic acid in flies fed with a high-fat diet, which was significantly influenced by the mating status of flies due to varied rearing conditions.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750953","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}