IF 3.9 3区医学

Aging-Us Pub Date : 2025-04-01 DOI: 10.18632/aging.206234

Yan Li, Fuxu Wang, Hongbo Zhao, Zhenwei Jia, Xiaoyan Liu, Guirong Cui, Tiejun Qin, Xiaoyang Kong

{"title":"Comprehensive genomic characterization of programmed cell death-related genes to predict drug resistance and prognosis for patients with multiple myeloma.","authors":"Yan Li, Fuxu Wang, Hongbo Zhao, Zhenwei Jia, Xiaoyan Liu, Guirong Cui, Tiejun Qin, Xiaoyang Kong","doi":"10.18632/aging.206234","DOIUrl":"https://doi.org/10.18632/aging.206234","url":null,"abstract":"Background: Multiple myeloma (MM) is a cancer that is difficult to be diagnosed and treated. This study aimed to identify programmed cell death (PCD)-related molecular subtypes of MM and to assess their impact on patients' prognosis, immune status, and drug sensitivity.Methods: We used the ConsensusClusterPlus method to classify molecular subtypes with prognostically relevant PCD genes from the MM patients screened. A prognostic model and a nomogram were established applying one-way COX regression analysis and LASSO Cox regression analysis. MM patients' sensitivity to chemotherapeutic agents was predicted for at-risk populations.Results: Six molecular subtypes were classified employing PCD-related genes, notably, three of them had a higher tendency for immune escape and two of them were correlated with a worse prognosis of MM. Furthermore, the C3 subtype had activated pathways such as oxidative phosphorylation and DNA repair, while the C2 and C4 subtypes had activated pathways related to apoptosis. The Risk score showed that the nomogram can correctly predict the OS for MM patients, in particular, patients in the high-risk group had low overall survival (OS). Pharmacovigilance analyses revealed that patients in the high-risk and low-risk groups had greater IC50 values for the drugs SB505124_1194 and AZD7762_1022, respectively.Conclusions: A 12-gene Risk score model developed with PCD-related genes can accurately predict the survival for MM patients. Our study provided potential targets and strategies for individualized treatment of MM.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Examining frailty phenotypes of community-dwelling older adults in Taiwan using the falls risk for older people in the community - Taiwan version (Tw-FROP-Com).

IF 3.9 3区医学

Aging-Us Pub Date : 2025-04-01 DOI: 10.18632/aging.206231

Ya-Mei Tzeng, Senyeong Kao, Wun-Sin Chen, Shueh-Fen Chen, Shan-Ru Li, Yu-Lung Chiu, Yu-Tien Chang, Yaw-Wen Chang

{"title":"Examining frailty phenotypes of community-dwelling older adults in Taiwan using the falls risk for older people in the community - Taiwan version (Tw-FROP-Com).","authors":"Ya-Mei Tzeng, Senyeong Kao, Wun-Sin Chen, Shueh-Fen Chen, Shan-Ru Li, Yu-Lung Chiu, Yu-Tien Chang, Yaw-Wen Chang","doi":"10.18632/aging.206231","DOIUrl":"https://doi.org/10.18632/aging.206231","url":null,"abstract":"Background: Falls are the second leading cause of accidental injury-related deaths among Taiwanese adults aged 65 and older. This study examined the association between Fried frailty phenotypes and fall risk in this population.Materials and methods: A cross-sectional study was conducted in Keelung City with 375 participants from an Elderly Fall Prevention Program. Frailty was assessed using the modified Fried criteria: weakness, slowness, exhaustion, low physical activity, and unintentional weight loss. Participants with 0-2 criteria were classified as non-frail, and those with 3 or more as frail. Fall risk was evaluated using the Taiwan version of the Falls Risk for Older People in the Community (Tw-FROP-Com), a 28-item tool scoring 0-60 across 13 risk factors.Results: Participants had a mean age of 75.4 ± 6.8 years; 76.0% were female, 18.7% were frail, and 32.7% had fallen in the past year. Those with a fall history had higher rates of weakness (56.7%), slowness (49.6%), and frailty (26.1%). Regression analysis showed that weakness (β = 0.64), slowness (β = 0.21), exhaustion (β = 1.28), unintentional weight loss (β = 3.99), and low physical activity (β = 0.88) were significantly associated with increased fall risk. Frailty explained over 50% of fall risk variance, with unintentional weight loss as the strongest predictor.Conclusion: Unintentional weight loss is the most significant predictor of fall risk among frailty traits. Individual frailty components better predict fall risk than composite frailty measures.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mesenchymal stem cell-specific Sirt1 overexpression prevents sarcopenia induced by 1,25-dihydroxyvitamin D deficiency.

IF 3.9 3区医学

Aging-Us Pub Date : 2025-03-31 DOI: 10.18632/aging.206232

Haiyun Chen, Biqi Ren, Jing Wang, Xingchen Liu, Xiangjiao Yi, David Goltzman, Dengshun Miao

{"title":"Mesenchymal stem cell-specific Sirt1 overexpression prevents sarcopenia induced by 1,25-dihydroxyvitamin D deficiency.","authors":"Haiyun Chen, Biqi Ren, Jing Wang, Xingchen Liu, Xiangjiao Yi, David Goltzman, Dengshun Miao","doi":"10.18632/aging.206232","DOIUrl":"https://doi.org/10.18632/aging.206232","url":null,"abstract":"Sarcopenia, characterized by an age-related decline in skeletal muscle mass and function, is closely linked to vitamin D deficiency. This study examines the role of Sirtuin 1 (Sirt1) and its regulation by vitamin D in preventing sarcopenia. Utilizing wild-type, 1α-hydroxylase knockout (1α(OH)ase-/-), and Sirt1 transgenic (Sirt1Tg) 1α(OH)ase-/- mice, we investigated muscle Sirt1 levels, muscle mass, fiber type, and senescence markers. Our results demonstrated that 1,25-Dihydroxyvitamin D (1,25(OH)2D3) upregulated Sirt1 and myogenic factor MyoD1 expression in C2C12 myoblasts via VDR-mediated transcription. Sirt1 overexpression in mesenchymal stem cells (MSCs) significantly mitigated muscle mass reduction, improved fiber cross-sectional area, and increased type II fiber numbers in 1α(OH)ase-/- mice. Mechanistically, 1,25(OH)2D3 promoted muscle cell health by enhancing Sirt1 expression, which in turn reduced muscle cell senescence and the senescence-associated secretory phenotype (SASP) through decreased levels of acetylated nuclear p53 and p65, maintaining their cytoplasmic localization. Additionally, Sirt1 overexpression accelerated muscle regeneration post-injury by increasing embryonic myosin heavy chain expression and cell proliferation. These findings underscore the therapeutic potential of targeting vitamin D and Sirt1 pathways to prevent sarcopenia, suggesting that supplementation with active vitamin D and consequent Sirt1 activation could be effective strategies for managing age-related muscle wasting.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential senolytic inhibition of normal versus Aβ-associated cholinesterases: implications in aging and Alzheimer's disease.

IF 3.9 3区医学

Aging-Us Pub Date : 2025-03-29 DOI: 10.18632/aging.206227

Sultan Darvesh, Meghan K Cash, Katrina Forrestall, Hillary Maillet, Dane Sands

{"title":"Differential senolytic inhibition of normal versus Aβ-associated cholinesterases: implications in aging and Alzheimer's disease.","authors":"Sultan Darvesh, Meghan K Cash, Katrina Forrestall, Hillary Maillet, Dane Sands","doi":"10.18632/aging.206227","DOIUrl":"https://doi.org/10.18632/aging.206227","url":null,"abstract":"Cellular senescence is a hallmark of aging and the age-related condition, Alzheimer's disease (AD). How senescence contributes to cholinergic and neuropathologic changes in AD remains uncertain. Furthermore, little is known about the relationship between senescence and cholinesterases (ChEs). Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are important in neurotransmission, cell cycle regulation, and AD amyloid-β (Aβ) pathology. Senolytic agents have shown therapeutic promise in AD models. Therefore, we evaluated in vitro and in silico activity of senolytics, dasatinib (1), nintedanib (2), fisetin (3), quercetin (4), GW2580 (5), and nootropic, meclofenoxate hydrochloride (6), toward AChE and BChE. As ChEs associated with AD pathology have altered biochemical properties, we also evaluated agents 1-6 in AD brain tissues. Enzyme kinetics showed agents 1, 3, 4, and 6 inhibited both ChEs, while 2 and 5 inhibited only AChE. Histochemistry showed inhibition of Aβ plaque-associated ChEs (1 and 2: both ChEs; 5: BChE; 6: AChE), but not normal neural-associated ChEs. Modeling studies showed 1-6 interacted with the same five binding locations of both ChEs, some of which may be allosteric sites. These agents may exert their beneficial effects, in part, by inhibiting ChEs associated with AD pathology and provide new avenues for development of next-generation inhibitors targeting pathology-associated ChEs.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The rodent aging interventions database (RAID): a data visualization tool for all studies reporting rodent lifespan extension.

IF 3.9 3区医学

Aging-Us Pub Date : 2025-03-27 DOI: 10.18632/aging.206228

Maximus V Peto, Anthony J Floyd, Ben Zealley, Aubrey D N J de Grey

{"title":"The rodent aging interventions database (RAID): a data visualization tool for all studies reporting rodent lifespan extension.","authors":"Maximus V Peto, Anthony J Floyd, Ben Zealley, Aubrey D N J de Grey","doi":"10.18632/aging.206228","DOIUrl":"https://doi.org/10.18632/aging.206228","url":null,"abstract":"Numerous studies have investigated the effects of various interventions on the lifespans of mice and rats. The design of future rodent lifespan extension experiments might consider experimental parameters used in earlier investigations, but finding and reviewing all previous experiments requires a substantial resource investment. Additionally, when studied collectively, the results of previous investigations might suggest fundamental mechanisms causing age-related degeneration. Here, we report our efforts to find and aggregate data from all research reports of lifespan extension in mice or rats, which we call the \"Rodent Aging Interventions Database\" (RAID). We identified studies for inclusion using complex PubMed queries and by nomination from our colleagues in the field. The relevant data from each study was manually extracted and recorded in a table. A publicly available, web-based software tool was then created to enable users to visualize and filter this data in a convenient manner. Our current dataset, covering publications up to October 2022, includes 121 unique studies reporting on 212 distinct intervention protocols that extended lifespan in mice or rats. We intend to periodically update our dataset as new rodent lifespan studies are reported. RAID is publicly available at https://levf.org/raid.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decreased surface receptors, function, and suboptimal osteoclasts-induced cell expansion in natural killer (NK) cells of elderly subjects.

IF 3.9 3区医学

Aging-Us Pub Date : 2025-03-26 DOI: 10.18632/aging.206226

Kawaljit Kaur, Anahid Jewett

{"title":"Decreased surface receptors, function, and suboptimal osteoclasts-induced cell expansion in natural killer (NK) cells of elderly subjects.","authors":"Kawaljit Kaur, Anahid Jewett","doi":"10.18632/aging.206226","DOIUrl":"https://doi.org/10.18632/aging.206226","url":null,"abstract":"Natural killer (NK) cells are known for their cytotoxic and cytokine secretion capabilities. The balance of activating and inhibitory receptors on their surface regulates NK cell function and survival. However, it is not fully understood how aging may modulate the levels of NK cell surface receptors ultimately affecting their interaction with other immune cells, especially with those known to activate and expand NK cells. Here, we report decreased levels of NK cells' surface receptors, cytotoxic function, and cytokine secretion in aged donors (75-85 years) as compared to younger donors (21-25 years). We used our previously established methodology to expand and supercharge NK cells from young and older individuals using osteoclasts (OCs) and probiotic bacteria. Significantly lower levels of NK cell expansion and functional activation were seen in NK cells from 75-85-year-old donors when compared to younger donors' NK cells. Surface receptors of OCs were also found to be decreased in 75-85-year-old donors compared to younger donors. In addition, OCs from 75-85-year-old donors induced lower levels of cell expansion and functional activation of NK cells when compared to OCs from younger donors. These findings illustrate defects in both peripheral blood-derived primary NK cells and OCs in older individuals; however, suppression appears to be more in NK cells when compared to OCs.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parallel patterns of age-related working memory impairment in marmosets and macaques.

IF 3.9 3区医学

Aging-Us Pub Date : 2025-03-24 DOI: 10.18632/aging.206225

Casey R Vanderlip, Megan L Jutras, Payton A Asch, Stephanie Y Zhu, Monica N Lerma, Elizabeth A Buffalo, Courtney Glavis-Bloom

{"title":"Parallel patterns of age-related working memory impairment in marmosets and macaques.","authors":"Casey R Vanderlip, Megan L Jutras, Payton A Asch, Stephanie Y Zhu, Monica N Lerma, Elizabeth A Buffalo, Courtney Glavis-Bloom","doi":"10.18632/aging.206225","DOIUrl":"10.18632/aging.206225","url":null,"abstract":"As humans age, some experience cognitive impairment while others do not. When impairment does occur, it is not expressed uniformly across cognitive domains and varies in severity across individuals. Translationally relevant model systems are critical for understanding the neurobiological drivers of this variability, which is essential to uncovering the mechanisms underlying the brain's susceptibility to the effects of aging. As such, non-human primates (NHPs) are particularly important due to shared behavioral, neuroanatomical, and age-related neuropathological features with humans. For many decades, macaque monkeys have served as the primary NHP model for studying the neurobiology of cognitive aging. More recently, the common marmoset has emerged as an advantageous model for this work due to its short lifespan that facilitates longitudinal studies. Despite their growing popularity as a model, whether marmosets exhibit patterns of age-related cognitive impairment comparable to those observed in macaques and humans remains unexplored. To address this major limitation for the development and evaluation of the marmoset as a model of cognitive aging, we directly compared working memory ability as a function of age in macaques and marmosets on the identical task. We also implemented varying delays to further tax working memory capacity. Our findings demonstrate that marmosets and macaques exhibit remarkably similar age-related working memory deficits, with macaques performing better than marmosets on longer delays. These results highlight the similarities and differences between the two most commonly used NHP models and support the value of the marmoset as a model for cognitive aging research within the neuroscience community.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of the metalloprotease ADAM19 as a novel senomorphic strategy to ameliorate gut permeability and senescence markers by modulating senescence-associated secretory phenotype (SASP).

IF 3.9 3区医学

Aging-Us Pub Date : 2025-03-20 DOI: 10.18632/aging.206224

Sudipta Bar, Tyler A U Hilsabeck, Blaine Pattavina, José Alberto López-Domínguez, Nathan Basisty, Joanna Bons, Mark Watson, Birgit Schilling, Judith Campisi, Pankaj Kapahi, Amit Sharma

{"title":"Inhibition of the metalloprotease ADAM19 as a novel senomorphic strategy to ameliorate gut permeability and senescence markers by modulating senescence-associated secretory phenotype (SASP).","authors":"Sudipta Bar, Tyler A U Hilsabeck, Blaine Pattavina, José Alberto López-Domínguez, Nathan Basisty, Joanna Bons, Mark Watson, Birgit Schilling, Judith Campisi, Pankaj Kapahi, Amit Sharma","doi":"10.18632/aging.206224","DOIUrl":"https://doi.org/10.18632/aging.206224","url":null,"abstract":"Accumulation of DNA damage can accelerate aging through cellular senescence. Previously, we established a Drosophila model to investigate the effects of radiation-induced DNA damage on the intestine. In this model, we examined irradiation-responsive senescence in the fly intestine. Through an unbiased genome-wide association study (GWAS) utilizing 156 strains from the Drosophila Genetic Reference Panel (DGRP), we identified meltrin (the drosophila orthologue of mammalian ADAM19) as a potential modulator of the senescence-associated secretory phenotype (SASP). Knockdown of meltrin resulted in reduced gut permeability, DNA damage, and expression of the senescence marker β-galactosidase (SA-β-gal) in the fly gut following irradiation. Additionally, inhibition of ADAM19 in mice using batimastat-94 reduced gut permeability and inflammation in the gut. Our findings extend to human primary fibroblasts, where ADAM19 knockdown or pharmacological inhibition decreased expression of specific SASP factors and SA-β-gal. Furthermore, proteomics analysis of the secretory factor of senescent cells revealed a significant decrease in SASP factors associated with the ADAM19 cleavage site. These data suggest that ADAM19 inhibition could represent a novel senomorphic strategy.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic and accelerated age in captive olive baboons (Papio anubis), and relationships with walking speed and fine motor performance. 人工饲养的橄榄狒狒（Papio anubis）的表观遗传和加速年龄，以及与行走速度和精细运动表现的关系。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-03-18 DOI: 10.18632/aging.206223

Sarah J Neal, Shannon Whitney, Soojin V Yi, Joe H Simmons

{"title":"Epigenetic and accelerated age in captive olive baboons (Papio anubis), and relationships with walking speed and fine motor performance.","authors":"Sarah J Neal, Shannon Whitney, Soojin V Yi, Joe H Simmons","doi":"10.18632/aging.206223","DOIUrl":"https://doi.org/10.18632/aging.206223","url":null,"abstract":"Epigenetic age, estimated by DNA methylation across the genome, reflects biological age. Accelerated age (i.e., an older methylation age than expected given chronological age) is an accepted aging biomarker in humans, showing robust associations with deleterious health outcomes, longevity, and mortality. However, data regarding age acceleration in nonhuman primates (NHPs), and relationships between NHP epigenetic age and behavioral indicators of aging, such as walking speed and fine motor performance, are sparse. We measured DNA methylation of 140 captive olive baboons (Papio anubis) (84% female, 3-20 years-old), estimated their epigenetic ages, and classified them as showing age acceleration or deceleration. We found that epigenetic age was strongly correlated with chronological age, and that approximately 27% of the sample showed age acceleration and 28% showed age deceleration. We subsequently examined relationships between epigenetic and accelerated age and walking speed (N=129) and fine motor performance (N=39). Older animals showed slower speeds and poorer motor performance. However, the difference between the epigenetic age and chronological age, referred to as delta age, was not a consistent predictor of walking speed or fine motor performance. These data highlight the need for further examination of age acceleration across NHP species, and the ways that age acceleration may (not) be related to indicators of aging in NHP models.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial oxidative stress or decreased autophagy in osteoblast lineage cells is not sufficient to mimic the deleterious effects of aging on bone mechanoresponsiveness.

IF 3.9 3区医学

Aging-Us Pub Date : 2025-03-18 DOI: 10.18632/aging.206213

Ana Resende-Coelho, Md Mohsin Ali, Alicen James, Aaron Warren, Landon Gatrell, Ilham Kadhim, Qiang Fu, Jinhu Xiong, Melda Onal, Maria Almeida

{"title":"Mitochondrial oxidative stress or decreased autophagy in osteoblast lineage cells is not sufficient to mimic the deleterious effects of aging on bone mechanoresponsiveness.","authors":"Ana Resende-Coelho, Md Mohsin Ali, Alicen James, Aaron Warren, Landon Gatrell, Ilham Kadhim, Qiang Fu, Jinhu Xiong, Melda Onal, Maria Almeida","doi":"10.18632/aging.206213","DOIUrl":"https://doi.org/10.18632/aging.206213","url":null,"abstract":"Exercise-induced mechanical load stimulates bone cells, including osteocytes, to promote bone formation. The bone response to loading is less effective with aging, but the cellular and molecular mechanisms responsible for the impaired mechanoresponsiveness remain unclear. Excessive mitochondrial reactive oxygen species (mtROS) and deficient autophagy are common aging mechanisms implicated in decreased bone formation in old mice. Here, we confirmed that the osteogenic effects of tibia compressive loading are lower in old versus young female mice. We also examined whether an increase in mtROS or decreased autophagy in osteoblast-lineage cells of adult female mice could mimic the deleterious effects of aging. To this end, we loaded mice lacking the antioxidant enzyme superoxide dismutase 2 (Sod2) or autophagy-related 7 (Atg7) in cells targeted by Osterix1 (Osx1)-Cre. Osteocytes in Atg7ΔOsx1 exhibited altered morphology and decreased osteocyte dendrite projections. Two weeks of loading increased cortical bone mass and bone formation rate at both periosteal and endosteal surfaces of Osx1-Cre control mice. Nonetheless, in both Atg7ΔOsx1 and Sod2ΔOsx1 mice the response to loading was identical to that observed in control mice, indicating that compromised Atg7-dependent autophagy or excessive mtROS are not sufficient to impair the bone response to tibial compressive loading. Thus, alternative mechanisms of aging might be responsible for the decreased response of the aged skeleton to mechanical stimuli. These findings also suggest that an intact osteocyte dendrite network is not required for the osteogenic response in this model of bone loading.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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