Aging Cell最新文献

{"title":"Disease Aggravation With Age in an Experimental Model of Multiple Sclerosis: Role of Immunosenescence","authors":"María Dema,&nbsp;Herena Eixarch,&nbsp;Arnau Hervera,&nbsp;Mireia Castillo,&nbsp;Luisa M. Villar,&nbsp;Xavier Montalban,&nbsp;Carmen Espejo","doi":"10.1111/acel.14491","DOIUrl":"10.1111/acel.14491","url":null,"abstract":"<p>The onset of multiple sclerosis (MS) in older individuals correlates with a higher risk of developing primary progressive MS, faster progression to secondary progressive MS, and increased disability accumulation. This phenomenon can be related to age-related changes in the immune system: with age, the immune system undergoes a process called immunosenescence, characterized by a decline in the function of both the innate and adaptive immune responses. This decline can lead to a decreased ability to control inflammation and repair damaged tissue. Additionally, older individuals often experience a shift toward a more pro-inflammatory state, known as inflammaging, which can exacerbate the progression of neurodegenerative diseases like MS. Therefore, age-related alterations in the immune system could be responsible for the difference in the phenotype of MS observed in older and younger patients. In this study, we investigated the effects of age on the immunopathogenesis of experimental autoimmune encephalomyelitis (EAE). Our findings indicate that EAE is more severe in aged mice due to a more inflammatory and neurodegenerative environment in the central nervous system. Age-related changes predominantly affect adaptive immunity, characterized by altered T cell ratios, a pro-inflammatory Th1 response, increased regulatory T cells, exhaustion of T cells, altered B cell antigen presentation, and reduced NK cell maturation and cytotoxicity. Transcriptomic analysis reveals that fewer pathways and transcription factors are activated with age in EAE. These findings allow us to identify potential therapeutic targets specific to elderly MS patients and work on their development in the future.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14491","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Zinc Limitation Dictates Lifespan and Reproduction Trade-Offs of Drosophila Mothers","authors":"Sweta Sarmah,&nbsp;Hannah Thi-Hong Hanh Truong,&nbsp;Gawain McColl,&nbsp;Richard Burke,&nbsp;Christen K. Mirth,&nbsp;Matthew D. W. Piper","doi":"10.1111/acel.14498","DOIUrl":"10.1111/acel.14498","url":null,"abstract":"<p>Dietary metal ions significantly influence the lifespan and reproduction of <i>Drosophila</i> females. In this study, we show that not adding any of the metal ions to the diet adversely affects reproduction and lifespan. By contrast, food with no added Zn negatively impacts reproduction but does not adversely affect maternal lifespan, indicating it can dictate resource reallocation between key fitness traits. Specifically, it indicates that female flies stop producing eggs to conserve their body Zn for somatic maintenance. Although these data show that flies can sense varying dietary Zn levels to adjust their physiology, they cannot maximise egg production when faced with a choice between food with no added Zn or food with sufficient Zn to support maximum reproduction. Nonetheless, they can choose to preferentially oviposit on Zn-containing food, perhaps indicating a strategy to assure offspring survival. We also uncovered a role for the <i>white</i> gene in sustaining high levels of egg viability when Zn is diluted in the diet. These insights into the role of dietary metal ions, particularly Zn, point to a central role for these dietary micronutrients to indicate environmental quality and so govern trade-offs between lifespan and reproduction in flies.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14498","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAV1 Exacerbates Renal Tubular Epithelial Cell Senescence by Suppressing CaMKK2/AMPK-Mediated Autophagy","authors":"Liya Sun,&nbsp;Lujun Xu,&nbsp;Tongyue Duan,&nbsp;Yiyun Xi,&nbsp;Zebin Deng,&nbsp;Shilu Luo,&nbsp;Chongbin Liu,&nbsp;Chen Yang,&nbsp;Huafeng Liu,&nbsp;Lin Sun","doi":"10.1111/acel.14501","DOIUrl":"10.1111/acel.14501","url":null,"abstract":"<p>Renal proximal tubular epithelial cell (PTEC) senescence and defective autophagy contribute to kidney aging, but the mechanisms remain unclear. Caveolin-1 (CAV1), a crucial component of cell membrane caveolae, regulates autophagy and is associated with cellular senescence. However, its specific role in kidney aging is poorly understood. In this study, we generated <i>Cav1</i> gene knockout mice and induced kidney aging using D-galactose (D-gal). The results showed that CAV1 expression increased in the renal cortex of the aging mice, which was accompanied by exacerbated renal interstitial fibrosis, elevated levels of senescence-associated proteins γH2AX and p16^INK4a, and increased β-galactosidase activity. Moreover, autophagy and AMPK phosphorylation in PTECs were reduced. These phenotypes were partially reversed in D-gal-induced <i>Cav1</i> knockout mice. Similar results were observed in D-gal-induced human proximal tubular epithelial (HK-2) cells, but these effects were blocked when AMPK activation was inhibited. Additionally, in CaMKK2 knockdown HK-2 cells, si<i>CAV1</i> failed to promote AMPK phosphorylation, whereas this effect persisted when STK11 was knocked down. Besides, we examined the phosphorylation of CaMKK2 and found that si<i>CAV1</i> increased its activity. Given that CaMKK2 activity is affected by intracellular Ca²⁺, we examined Ca²⁺ levels in HK-2 cells and found that D-gal treatment reduced intracellular Ca²⁺ concentration, but <i>CAV1</i> knockdown did not alter these levels. Through GST pull-down assays, we demonstrated a direct interaction between CAV1 and CaMKK2. In conclusion, these findings suggest that CAV1 exacerbates renal tubular epithelial cell senescence by directly interacting with CaMKK2, suppressing its activity and AMPK-mediated autophagy via a Ca²⁺-independent pathway.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel framework to build saliva-based DNA methylation biomarkers: Quantifying systemic chronic inflammation as a case study","authors":"Lisa J. Schmunk,&nbsp;Toby P. Call,&nbsp;Daniel L. McCartney,&nbsp;Hira Javaid,&nbsp;Waylon J. Hastings,&nbsp;Vanja Jovicevic,&nbsp;Dragoljub Kojadinović,&nbsp;Natacha Tomkinson,&nbsp;Eliska Zlamalova,&nbsp;Kirsty C. McGee,&nbsp;Jack Sullivan,&nbsp;Archie Campbell,&nbsp;Andrew M. McIntosh,&nbsp;Veronika Óvári,&nbsp;Karl Wishart,&nbsp;Christian E. Behrens,&nbsp;Emma Stone,&nbsp;Miloš Gavrilov,&nbsp;Rob Thompson,&nbsp;Hurdle bio-infrastructure team,&nbsp;Thomas Jackson,&nbsp;Janet M. Lord,&nbsp;Thomas M. Stubbs,&nbsp;Riccardo E. Marioni,&nbsp;Daniel E. Martin-Herranz","doi":"10.1111/acel.14444","DOIUrl":"10.1111/acel.14444","url":null,"abstract":"<p>Accessible and non-invasive biomarkers that measure human ageing processes and the risk of developing age-related disease are paramount in preventative healthcare. Here, we describe a novel framework to train saliva-based DNA methylation (DNAm) biomarkers that are reproducible and biologically interpretable. By leveraging a reliability dataset with replicates across tissues, we demonstrate that it is possible to transfer knowledge from blood DNAm to saliva DNAm data using DNAm proxies of blood proteins (EpiScores). We apply these methods to create a new saliva-based epigenetic clock (InflammAge) that quantifies systemic chronic inflammation (SCI) in humans. Using a large blood DNAm human cohort with linked electronic health records and over 18,000 individuals (Generation Scotland), we demonstrate that InflammAge significantly associates with all-cause mortality, disease outcomes, lifestyle factors, and immunosenescence; in many cases outperforming the widely used SCI biomarker C-reactive protein (CRP). We propose that our biomarker discovery framework and InflammAge will be useful to improve understanding of the molecular mechanisms underpinning human ageing and to assess the impact of gero-protective interventions.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic modulation rescues neurodevelopmental deficits in Syngap1+/− mice","authors":"Akash Kumar Singh,&nbsp;Ila Joshi,&nbsp;Neeharika M. N. Reddy,&nbsp;Sushmitha S. Purushotham,&nbsp;M. Eswaramoorthy,&nbsp;Madavan Vasudevan,&nbsp;Sourav Banerjee,&nbsp;James P. Clement,&nbsp;Tapas K. Kundu","doi":"10.1111/acel.14408","DOIUrl":"10.1111/acel.14408","url":null,"abstract":"<p>SYNGAP1 is a Ras GTPase-activating protein that plays a crucial role during brain development and in synaptic plasticity. Sporadic heterozygous mutations in <i>SYNGAP1</i> affect social and emotional behaviour observed in intellectual disability (ID) and autism spectrum disorder (ASD). Although neurophysiological deficits have been extensively studied, the epigenetic landscape of <i>SYNGAP1</i> mutation-mediated intellectual disability is unexplored. Here, we have found that the p300/CBP specific acetylation marks of histones are significantly repressed in the hippocampus of adolescent <i>Syngap1</i>^<i>+/−</i> mice. Additionally, we observed decreased dendritic branching of newly born DCX⁺ neurons in these mice, suggesting altered adult hippocampal neurogenesis. To establish the causal relationship of <i>Syngap1</i>^<i>+/−</i> phenotype and the altered histone acetylation signature we have treated 2–4 months old <i>Syngap1</i>^<i>+/−</i> mice with glucose-derived carbon nanosphere (CSP) conjugated potent small molecule activator (TTK21) of p300/CBP lysine acetyltransferase (CSP-TTK21). The enhancement of the p300/CBP specific acetylation marks of histones by CSP-TTK21 restored synaptic functions, increased dendritic branching of DCX⁺ neurons, enables the capability to reorganise cortical circuits in response to change in the sensory stimuli, and improves behavioural measures in <i>Syngap1</i>^<i>+/−</i> mice that are very closely comparable to wild type littermates. Further, hippocampal RNA-Seq analysis of these mice revealed that the expression of many critical genes such as Adcy1, Ntrk3, Egr1, and Foxj1 which are key regulators of synaptic plasticity and neurogenesis and are well associated with ID/ASD reversed upon CSP-TTK21 treatment. This study could be the first demonstration of the reversal of autistic behaviour and neural wiring upon the modulation of altered epigenetic modification(s).</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raman Spectroscopy in Cellular and Tissue Aging Research","authors":"Jeong Hee Kim,&nbsp;Daejong Yang,&nbsp;Seungman Park","doi":"10.1111/acel.14494","DOIUrl":"10.1111/acel.14494","url":null,"abstract":"<p>The establishment of various molecular, physiological, and genetic markers for cellular senescence and aging-associated conditions has progressed the aging study. To identify such markers, a combination of optical, proteomic-, and sequencing-based tools is primarily used, often accompanying extrinsic labels. Yet, the tools for clinical detection at the molecular, cellular, and tissue levels are still lacking which profoundly hinders advancements in the specific detection and timely prevention of aging-related diseases and pathologies. Raman spectroscopy, with its capability for rapid, label-free, and non-invasive analysis of molecular compositions and alterations in aging cells and tissues, holds considerable promise for in vivo applications. In this review, we present recent advancements in the application of Raman spectroscopy to the study of aging in cells and tissues. We explore the use of Raman spectroscopy and related techniques for detecting cellular aging and senescence, focusing on the molecular alterations that accompany these processes. Subsequently, we provide a review of the application of Raman spectroscopy in identifying aging-related changes in various molecules within tissues and organs.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Exercise Decreases Complement-Mediated Synaptic Loss and Protects Against Cognitive Impairment by Inhibiting Microglial Tmem9-ATP6V0D1 in Alzheimer's Disease","authors":"Shiyin Li,&nbsp;Mingyue Li,&nbsp;Ge Li,&nbsp;Lili Li,&nbsp;Xiaofeng Yang,&nbsp;Zejie Zuo,&nbsp;Liying Zhang,&nbsp;Xiquan Hu,&nbsp;Xiaofei He","doi":"10.1111/acel.14496","DOIUrl":"10.1111/acel.14496","url":null,"abstract":"<p>Physical exercise is known to slow synaptic neurodegeneration and cognitive aging in Alzheimer's disease (AD). The benefits of physical exercise are related to reduced amyloid beta (A<i>β</i>) deposition and increased synaptic plasticity. Yet little is known about the mechanisms that mediate these effects. Here, we show that physical exercise down-regulated the microglial Tmem9 protein, inhibited C1q activation, and decreased C1q-dependent microglial synapse engulfment, eventually ameliorating cognitive impairment in 5xFAD mice. Furthermore, using oA<i>β</i> cultured-BV2 in vitro, we show that downregulation of microglial Tmem9 was sufficient to restrain complement activity and decrease microglia-mediated synaptic loss, whereas overexpression of microglial Tmem9 tended to promote complement activation and induced synaptic loss, abolishing exercise-associated protection. Finally, we show that microglial Tmem9 contributed to complement activation by regulating ATP6V0D1, a vesicular (H⁺) ATP-dependent proton pump (V-ATPase) subunit that regulates V-ATPase assembly. Together, our results demonstrate that exercise is a potential treatment for AD patients. In an AD mouse model, it decreased the levels of microglial Tmem9 to inhibit the activation of complement, alleviated complement-dependent synaptic loss, and eventually ameliorated emotional and cognitive disorders.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting CRM1 for Progeria Syndrome Therapy","authors":"Adriana Soto-Ponce,&nbsp;Marlon De Ita,&nbsp;Susana Castro-Obregón,&nbsp;Diego Cortez,&nbsp;Yosef Landesman,&nbsp;Jonathan J. Magaña,&nbsp;Susana Gonzalo,&nbsp;Tania Zavaleta,&nbsp;Angelica Soberano-Nieto,&nbsp;Juan Unzueta,&nbsp;Isabel Arrieta-Cruz,&nbsp;Porfirio Nava,&nbsp;Aurora Candelario-Martínez,&nbsp;Ian García-Aguirre,&nbsp;Bulmaro Cisneros","doi":"10.1111/acel.14495","DOIUrl":"10.1111/acel.14495","url":null,"abstract":"<p>Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by progerin, a mutant variant of lamin A. Progerin anchors aberrantly to the nuclear envelope disrupting a plethora of cellular processes, which in turn elicits senescence. We previously showed that the chromosomal region maintenance 1 (CRM1)-driven nuclear export pathway is abnormally enhanced in patient-derived fibroblasts, due to overexpression of CRM1. Interestingly, pharmacological inhibition of CRM1 using leptomycin B rescues the senescent phenotype of HGPS fibroblasts, delineating CRM1 as a potential therapeutic target against HGPS. As a proof of concept, we analyzed the beneficial effects of pharmacologically modulating CRM1 in dermal fibroblasts from HGPS patients and the <i>LMNA^G609G/G609G</i> mouse, using the first-in-class selective inhibitor of CRM1 termed selinexor. Remarkably, treatment of HGPS fibroblasts with selinexor mitigated senescence and promoted progerin clearance via autophagy, while at the transcriptional level restored the expression of numerous differentially-expressed genes and rescued cellular processes linked to aging. In vivo, oral administration of selinexor to the progeric mouse resulted in decreased progerin immunostaining in the liver and aorta, decreased progerin levels in most liver, lung and kidney samples analyzed by immunoblotting, and improved aortic histopathology. Collectively our data indicate that selinexor exerts its geroprotective action by at least two mechanisms: normalizing the nucleocytoplasmic partition of proteins with a downstream effect on the aging-associated transcriptome and decreasing progerin levels. Further investigation of the overall effect of selinexor on <i>Lmna^G609G/G609G</i> mouse physiology, with emphasis in cardiovascular function is warranted, to determine its therapeutic utility for HGPS and aging-associated disorders characterized by CRM1 overactivity.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimising Age-Specific Insulin Signalling to Slow Down Reproductive Ageing Increases Fitness in Different Nutritional Environments","authors":"Zahida Sultanova,&nbsp;Aykut Shen,&nbsp;Katarzyna Hencel,&nbsp;Hanne Carlsson,&nbsp;Zoe Crighton,&nbsp;Daniel Clifton,&nbsp;Alper Akay,&nbsp;Alexei A. Maklakov","doi":"10.1111/acel.14481","DOIUrl":"10.1111/acel.14481","url":null,"abstract":"<p>The developmental theory of ageing proposes that age-specific decline in the force of natural selection results in suboptimal levels of gene expression in adulthood, leading to functional senescence. This theory explicitly predicts that optimising gene expression in adulthood can ameliorate functional senescence and improve fitness. Reduced insulin/IGF-1 signalling (rIIS) extends the reproductive lifespan of <i>Caenorhabditis elegans</i> at the cost of reduced reproduction. Here, we show that adulthood-only rIIS improves late-life reproduction without any detrimental effects on other life-history traits in both benign and stressful conditions. Remarkably, we show that rIIS additively extends late-life reproduction and lifespan when animals are exposed to a fluctuating food environment—intermittent fasting (IF)—resulting in reduced food intake in early adulthood. Full factorial genome-wide RNA-Seq across the life course demonstrated that IF and rIIS modulate the age-specific expression of pro-longevity genes. IF, rIIS and combined IF + rIIS treatment downregulated genes involved in biosynthesis in early life and differentially regulated immunity genes in later life. Importantly, combined IF + rIIS treatment uniquely regulated a large cluster of genes in mid-life that are associated with immune response. These results suggest that optimising gene expression in adulthood can decelerate reproductive ageing and increase fitness.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 5","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifetime age-related changes in clinical laboratory results, aging clocks and mortality predictors in 2412 Golden Retrievers","authors":"Kevin Perez,&nbsp;Brenna Swafford,&nbsp;Julia Labadie,&nbsp;Alejandro Ocampo","doi":"10.1111/acel.14438","DOIUrl":"10.1111/acel.14438","url":null,"abstract":"<p>In this study, we investigated age-related changes in clinical laboratory data and their association with mortality in dogs from the Golden Retriever Lifetime Study. By analyzing complete blood count (CBC) and biochemistry data from 2′412 Golden Retrievers over 16,678 visits, we observed significant changes during the first 2 years of life and throughout aging. Based on these observations, we developed a biological aging clock using a LASSO model to predict age based on blood markers, achieving an accuracy of <i>R</i> = 0.78. Although the biological age clock and pace of aging did not significantly improve mortality prediction, a model incorporating all blood biomarkers showed better predictive power for lifetime (C-index = 0.763) and 1-year mortality (AUC = 0.817). Our findings underscore the importance of comprehensive blood analysis for aging and mortality prediction in dogs and open the door for the development of novel methods to investigate aging in companion animals.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 4","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}