Aging Cell最新文献

{"title":"Pro-inflammatory cytokine 11 plays a pivotal role in inflammaging-associated pathologies","authors":"José M. Izquierdo","doi":"10.1111/acel.14360","DOIUrl":"10.1111/acel.14360","url":null,"abstract":"<p>Chronic sterile inflammation contributes to aging-associated pathologies/malignancies like cancer and autoimmune disorders. In their recent Nature article, Widjaja et al. established the pro-inflammatory, pro-fibrotic cytokine 11 (IL11) as a regulatory driver/hub of aging-associated inflammation (inflammaging) in mice. Genetic and pharmacological IL11 blockade reduces inflammaging, improving healthspan, lifespan, and longevity in male and female mice, highlighting IL11 as a new inflammatory aging clock and a potential molecular target in inflammaging-associated human degenerative diseases.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370332","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":"Dysregulated nicotinamide adenine dinucleotide metabolome in patients hospitalized with COVID-19","authors":"Rodrigo J. Valderrábano,&nbsp;Benjamin Wipper,&nbsp;Karol Mateusz Pencina,&nbsp;Marie Migaud,&nbsp;Yili Valentine Shang,&nbsp;Nancy K. Latham,&nbsp;Monty Montano,&nbsp;James M. Cunningham,&nbsp;Lauren Wilson,&nbsp;Liming Peng,&nbsp;Yusnie Memish-Beleva,&nbsp;Avantika Bhargava,&nbsp;Pamela M. Swain,&nbsp;Phoebe Lehman,&nbsp;Siva Lavu,&nbsp;David J. Livingston,&nbsp;Shalender Bhasin","doi":"10.1111/acel.14326","DOIUrl":"10.1111/acel.14326","url":null,"abstract":"<p>Nicotinamide adenine dinucleotide (NAD⁺) depletion has been postulated as a contributor to the severity of COVID-19; however, no study has prospectively characterized NAD⁺ and its metabolites in relation to disease severity in patients with COVID-19. We measured NAD⁺ and its metabolites in 56 hospitalized patients with COVID-19 and in two control groups without COVID-19: (1) 31 age- and sex-matched adults with comorbidities, and (2) 30 adults without comorbidities. Blood NAD⁺ concentrations in COVID-19 group were only slightly lower than in the control groups (<i>p</i> &lt; 0.05); however, plasma 1-methylnicotinamide concentrations were significantly higher in patients with COVID-19 (439.7 ng/mL, 95% CI: 234.0, 645.4 ng/mL) than in age- and sex-matched controls (44.5 ng/mL, 95% CI: 15.6, 73.4) and in healthy controls (18.1 ng/mL, 95% CI 15.4, 20.8; <i>p</i> &lt; 0.001 for each comparison). Plasma nicotinamide concentrations were also higher in COVID-19 group and in controls with comorbidities than in healthy control group. Plasma concentrations of 2-methyl-2-pyridone-5-carboxamide (2-PY), but not NAD⁺, were significantly associated with increased risk of death (HR = 3.65; 95% CI 1.09, 12.2; <i>p</i> = 0.036) and escalation in level of care (HR = 2.90, 95% CI 1.01, 8.38, <i>p</i> = 0.049). RNAseq and RTqPCR analyses of PBMC mRNA found upregulation of multiple genes involved in NAD⁺ synthesis as well as degradation, and dysregulation of NAD⁺-dependent processes including immune response, DNA repair, metabolism, apoptosis/autophagy, redox reactions, and mitochondrial function. Blood NAD⁺ concentrations are modestly reduced in COVID-19; however, NAD⁺ turnover is substantially increased with upregulation of genes involved in both NAD⁺ biosynthesis and degradation, supporting the rationale for NAD+ augmentation to attenuate disease severity.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 12","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360808","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":"Sirtuin 3 reinforces acylcarnitine metabolism and maintains thermogenesis in brown adipose tissue of aging mice","authors":"Kuiliang Zhang,&nbsp;Yucheng Wang,&nbsp;Yujie Sun,&nbsp;Lamei Xue,&nbsp;Yu Wang,&nbsp;Chenzhipeng Nie,&nbsp;Mingcong Fan,&nbsp;Haifeng Qian,&nbsp;Hao Ying,&nbsp;Li Wang,&nbsp;Yan Li","doi":"10.1111/acel.14332","DOIUrl":"10.1111/acel.14332","url":null,"abstract":"<p>Acylcarnitine (ACar) is a novel fuel source for activating thermogenesis in brown adipose tissue (BAT). However, whether ACar metabolism underlies BAT thermogenesis decline with aging remain unclear. Here, the L-carnitine-treated young and aging mice were used to investigate the effects of activation of ACar metabolism on BAT thermogenesis during aging. We showed that long term L-carnitine feeding, which results in an elevation in circulating ACar levels, failed to improve cold sensitivity of aging mice, which still displayed impaired thermogenesis and ACar metabolism in interscapular BAT (iBAT). The RNA-sequencing was used to identify the key regulator for the response of aging mice to LCar induced activation of ACar metabolism in BAT, and we identified Sirt3 as a key regulator for the response of aging mice to L-carnitine induced activation of ACar metabolism in iBAT. Then the adipose-specific Sirt3 knockout (Sirt3 AKO) mice were used to investigate the role of Sirt3 in ACar metabolism and thermogenesis of BAT and explore the underlying mechanism, and the results showed that Sirt3 AKO mice displayed defective ACar metabolism and thermogenesis in iBAT. Mechanically, Sirt3 regulated ACar metabolism via HIF1α-PPARα signaling pathway to promote iBAT thermogenesis, and knockdown or inhibition of HIF1α ameliorated impaired ACar metabolism and thermogenesis of iBAT in the absence of Sirt3. Collectively, we propose that Sirt3 regulated ACar metabolism is critical in maintaining thermogenesis in BAT of aging mice, which can promote the development of anti-aging intervention strategy.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 12","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337679","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":"Emerging signs of Alzheimer-like tau hyperphosphorylation and neuroinflammation in the brain post recovery from COVID-19","authors":"Xuetao Qi,&nbsp;Shulu Yuan,&nbsp;Jiuyang Ding,&nbsp;Weiqi Sun,&nbsp;Yajiao Shi,&nbsp;Yuanwei Xing,&nbsp;Zilong Liu,&nbsp;Yun Yao,&nbsp;Su Fu,&nbsp;Baofei Sun,&nbsp;Xiaolan Qi,&nbsp;Bing Xia,&nbsp;Fengyu Liu,&nbsp;Ming Yi,&nbsp;Jian Mao,&nbsp;You Wan,&nbsp;Jie Zheng","doi":"10.1111/acel.14352","DOIUrl":"10.1111/acel.14352","url":null,"abstract":"<p>Coronavirus disease 2019 (COVID-19) has been suggested to increase the risk of memory decline and Alzheimer's disease (AD), the main cause of dementia in the elderly. However, direct evidence about whether COVID-19 induces AD-like neuropathological changes in the brain, especially post recovery from acute infection, is still lacking. Here, using postmortem human brain samples, we found abnormal accumulation of hyperphosphorylated tau protein in the hippocampus and medial entorhinal cortex within 4–13 months post clinically recovery from acute COVID-19, together with prolonged activation of glia cells and increases in inflammatory factors, even though no SARS-COV-2 invasion was detected in these regions. By contrast, COVID-19 did not change beta-amyloid deposition and hippocampal neuron number, and had limited effects on AD-related pathological phenotypes in olfactory circuits including olfactory bulb, anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral entorhinal cortex. These results provide neuropathological evidences linking COVID-19 with prognostic increase of risk for AD.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337677","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":"Tissue-specific functions of MSCs are linked to homeostatic muscle maintenance and alter with aging","authors":"Tamaki Kurosawa,&nbsp;Madoka Ikemoto-Uezumi,&nbsp;Yuki Yoshimoto,&nbsp;Keitaro Minato,&nbsp;Noriyuki Kaji,&nbsp;Takashi Chaen,&nbsp;Eiji Hase,&nbsp;Takeo Minamikawa,&nbsp;Takeshi Yasui,&nbsp;Kazuhide Horiguchi,&nbsp;Satoshi Iino,&nbsp;Masatoshi Hori,&nbsp;Akiyoshi Uezumi","doi":"10.1111/acel.14299","DOIUrl":"10.1111/acel.14299","url":null,"abstract":"<p>Mesenchymal stromal cells (MSCs), also known as fibro-adipogenic progenitors, play a critical role in muscle maintenance and sarcopenia development. Although analogous MSCs are present in various tissues, recent single-cell RNA-seq studies have revealed the inter-tissue heterogeneity of MSCs. However, the functional significance of MSC heterogeneity and its role in aging remain unclear. Here, we investigated the properties of MSCs and their age-related changes in seven mouse tissues through histological, cell culture, and genetic examinations. The tissue of origin had a greater impact on the MSC transcriptome than aging. By first analyzing age-related changes, we found that <i>Kera</i> is exclusively expressed in muscle MSCs and significantly down-regulated by aging. <i>Kera</i> knockout mice recapitulated some sarcopenic phenotypes including reduced muscle mass and specific force, revealing the functional importance of <i>Kera</i> in the maintenance of muscle youth. These results suggest that MSCs have tissue-specific supportive functions and that deterioration in these functions may trigger tissue aging.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"23 11","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337681","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 longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring","authors":"Todd W. Dowrey,&nbsp;Samuel F. Cranston,&nbsp;Nicholas Skvir,&nbsp;Yvonne Lok,&nbsp;Brian Gould,&nbsp;Bradley Petrowitz,&nbsp;Daniel Villar,&nbsp;Jidong Shan,&nbsp;Marianne James,&nbsp;Mark Dodge,&nbsp;Anna C. Belkina,&nbsp;Richard M. Giadone,&nbsp;Sofiya Milman,&nbsp;Paola Sebastiani,&nbsp;Thomas T. Perls,&nbsp;Stacy L. Andersen,&nbsp;George J. Murphy","doi":"10.1111/acel.14351","DOIUrl":"10.1111/acel.14351","url":null,"abstract":"<p>Centenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models of <i>human</i> aging and resilience to disease that allow for the testing of potential interventions are virtually non-existent. We obtained and characterized over 96 centenarian and offspring peripheral blood samples including those connected to functional independence data highlighting resistance to disability and cognitive impairment. Targeted methylation arrays were used in molecular aging clocks to compare and contrast differences between biological and chronological age in these specialized subjects. Isolated peripheral blood mononuclear cells (PBMCs) from 20 of these subjects were then successfully reprogrammed into high-quality induced pluripotent stem cell (iPSC) lines which were functionally characterized for pluripotency, genomic stability, and the ability to undergo directed differentiation. The result of this work is a one-of-a-kind resource for studies of human longevity and resilience that can fuel the discovery and validation of novel therapeutics for aging-related disease.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337676","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":"Proteomic analysis across aged tissues reveals distinct signatures and the crucial involvement of midgut barrier function in the regulation of aging","authors":"Congying Zhang,&nbsp;Jinlong Wang,&nbsp;Tianzhao Yao,&nbsp;Jiaxin Hu,&nbsp;Feifei Sun,&nbsp;Chunlu Feng,&nbsp;Zhendong Sun,&nbsp;Yuzhuo Shao,&nbsp;Zhu Wang,&nbsp;Jiarui Wu,&nbsp;Yunpeng Huang","doi":"10.1111/acel.14344","DOIUrl":"10.1111/acel.14344","url":null,"abstract":"<p>The process of aging is a natural phenomenon characterized by gradual deterioration in biological functions and systemic homeostasis, which can be modulated by both genetic and environmental factors. Numerous investigations conducted on model organisms, including nematodes, flies, and mice, have elucidated several pivotal aging pathways, such as insulin signaling and AMPK signaling. However, it remains uncertain whether the regulation of the aging process is uniform or diverse across different tissues and whether manipulating the same aging factor can result in consistent outcomes in various tissues. In this study, we utilize the <i>Drosophila</i> organism to investigate tissue-specific proteome signatures during the aging process. Although distinct proteins undergo changes in aged tissues, certain common altered functional networks are constituently identified across different tissues, including the decline of the mitochondrial ribosomal network, autophagic network, and anti-ROS defense networks. Furthermore, downregulation of insulin receptor (InR) in the midguts, muscle, and central nervous system (CNS) of flies leads to a significant extension in fly lifespans. Notably, despite manipulating the same aging gene InR, diverse alterations in proteins are observed across different tissues. Importantly, knockdown of InR in the midguts leads to a distinct proteome compared with other tissues, resulting in enhanced actin nucleation and glutathione metabolism, while attenuating age-related elevation of serine proteases. Consequently, knockdown of InR results in rejuvenation of the integrity of the midgut barrier and augmentation of anti-ROS defense capabilities. Our findings suggest that the barrier function of the midgut plays a pivotal role in defending against aging, underscoring the paramount importance of maintaining optimal gut physiology to effectively delay the aging process. Moreover, when considering age-related changes across various tissues, it is more reasonable to identify functional networks rather than focusing solely on individual proteins.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337678","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":"Temperature-dependent lifespan extension is achieved in miR-80-deleted Caenorhabditis elegans by NLP-45 to modulate endoplasmic reticulum unfolded protein responses","authors":"Chunlin Zhao,&nbsp;Jintao Luo,&nbsp;Yuqiang Zhang,&nbsp;Yong Yu","doi":"10.1111/acel.14345","DOIUrl":"10.1111/acel.14345","url":null,"abstract":"<p>MicroRNA plays a crucial role in post-transcriptional gene regulation and has recently emerged as a factor linked to aging, but the underlying regulatory mechanisms remain incompletely understood. In this study, we observed lifespan-extending effects in <i>miR-80</i>-deficient <i>Caenorhabditis elegans</i> at 20°C but not 25°C. At 20°C, <i>miR-80</i> deletion leads to NLP-45 upregulation, which positively correlates to increased <i>abu</i> transcripts and extended lifespan. Supportively, we identified <i>miR-80</i> binding regions in the 5′ and 3’ UTR of <i>nlp-45</i>. As the temperature rises to 25°C, wildtype increases <i>miR-80</i> levels, but removal of <i>miR-80</i> is accompanied by decreased <i>nlp-45</i> expression, suggesting intervention from other temperature-sensitive mechanisms. These findings support the concept that microRNAs and neuropeptide-like proteins can form molecular regulatory networks involving downstream molecules to regulate lifespan, and such regulatory effects vary on environmental conditions. This study unveils the role of an axis of <i>miR-80</i>/NLP-45/UPR^ER components in regulating longevity, offering new insights on strategies of aging attenuation and health span prolongation.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337680","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":"Aging disrupts locus coeruleus-driven norepinephrine transmission in the prefrontal cortex: Implications for cognitive and motor decline","authors":"Evgeny Budygin,&nbsp;Valentina Grinevich,&nbsp;Zhong-Min Wang,&nbsp;María Laura Messi,&nbsp;William Ryan Meeker,&nbsp;Jie Zhang,&nbsp;William Matthew Stewart,&nbsp;Carol Milligan,&nbsp;Osvaldo Delbono","doi":"10.1111/acel.14342","DOIUrl":"10.1111/acel.14342","url":null,"abstract":"<p>The locus coeruleus (LC)-prefrontal cortex (PFC) circuitry is crucial for cognition, planning, posture and mobility. This study examines the role of norepinephrine (NE) in elucidating the neurobiological basis of age-related cognitive and motor declines. Aged mice exhibited reduced spatial learning, impaired memory, decreased physical endurance, and notable changes in locomotor behavior. The neurochemical foundations of these deficits were investigated through fast-scan cyclic voltammetry to measure NE release in the PFC and LC, both in vivo and in brain slices. Additionally, oxygen levels were monitored as a proxy for PFC neuronal function, and NE levels were analyzed in the extracellular space via microdialysis and total content in the PFC. Aged mice exhibited a frequency-dependent increase in NE release in the PFC upon LC stimulation, suggesting alterations in neural responsiveness due to aging. We also recorded slower NE reuptake rates and increased NE content and neuronal activity, indicated by higher oxygen levels and facilitated neuron activation due to membrane depolarization recorded via whole-cell patch-clamp. To understand the basis for LC-driven NE surges in the PFC with aging, we examined the expression levels of two proteins critical for presynaptic NE release and NE reuptake: the α2a-adrenergic receptor and the NE transporter. Both showed a significant decrease in the PFC with aging. These findings support the concept that aging significantly alters the structural and functional dynamics within the LC-PFC neural circuit, impacting NE modulation and neuronal activity, which may underlie the observed declines in cognitive and motor functions in aging populations.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306718","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":"2'-Fucosyllactose attenuates aging-related metabolic disorders through modulating gut microbiome-T cell axis","authors":"Ang Li,&nbsp;Ruixin Kou,&nbsp;Ruishan Wang,&nbsp;Jin Wang,&nbsp;Bowei Zhang,&nbsp;Jingmin Liu,&nbsp;Yaozhong Hu,&nbsp;Shuo Wang","doi":"10.1111/acel.14343","DOIUrl":"10.1111/acel.14343","url":null,"abstract":"<p>Aging-related metabolic disorders seriously affect the lifespan of middle-aged and older people, potentially due to disruptions in the adaptive immune and gut microbial profiles. Dietary intervention offers a promising strategy for maintaining metabolic health. This study aimed to investigate the ameliorative effect of 2′-fucosyllactose (2'-FL) on aging-induced metabolic dysfunction and the underlying mechanisms. The results revealed that 2'-FL significantly relieved aging-related metabolic disorders, including weight gain, lipid deposition, dyslipidemia, glucose intolerance, systemic inflammation, and abnormal hepatic metabolism. Flow cytometry analysis revealed a significant reduction in T cytotoxic (Tc), T helper (Th), and regulatory T (Treg) cells and a significant increase in Th17 cells in aged mice, while 2'-FL relieved the aging-induced proportional changes in Th and Th17 subtypes. The aging intestinal microecology was characterized by higher Th17/Treg ratios, impaired gut barrier function, lower gut bacterial diversity, decreased abundance of beneficial genera including <i>Ligilactobacillus</i>, <i>Colidextribacter</i>, <i>Mucispirillum</i>, and <i>Lachnoclostridium</i>, and increased abundance of harmful bacteria including <i>Turicibacter</i> and <i>Desulfovibrio</i>, which was ameliorated by 2'-FL treatment. These findings highlight that 2'-FL is an ideal dietary prebiotic for improving aging-related metabolic disorders by modulating both the adaptive immune system and the gut microbial profile.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277478","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}