Mitochondria are metabolic and signalling hubs that integrate a plethora of interconnected processes to maintain cell homeostasis. They are also dormant mediators of inflammation and cell death, and with aging damages affecting mitochondria gradually accumulate, resulting in the manifestation of age-associated disorders. In addition to coordinate multiple intracellular functions, mitochondria mediate intercellular and inter-organ cross talk in different physiological and stress conditions. To fulfil this task, mitochondrial signalling has evolved distinct and complex conventional and unconventional routes of horizontal/vertical mitochondrial transfer. In this regard, great interest has been focused on the ability of extracellular vesicles (EVs), such as exosomes and microvesicles, to carry selected mitochondrial cargoes to target cells, in response to internal and external cues. Over the past years, the field of mitochondrial EVs (mitoEVs) has grown exponentially, revealing unexpected heterogeneity of these structures associated with an ever-expanding mitochondrial function, though the full extent of the underlying mechanisms is far from being elucidated. Therefore, emerging subsets of EVs encompass exophers, migrasomes, mitophers, mitovesicles, and mitolysosomes that can act locally or over long-distances to restore mitochondrial homeostasis and cell functionality, or to amplify disease. This review provides a comprehensive overview of our current understanding of the biology and trafficking of MitoEVs in different physiological and pathological conditions. Additionally, a specific focus on the role of mitoEVs in aging and the onset and progression of different age-related diseases is discussed.
{"title":"Mitochondrial Extracellular Vesicles (mitoEVs): Emerging mediators of cell-to-cell communication in health, aging and age-related diseases.","authors":"Roberto Iorio , Sabrina Petricca , Giovanna Di Emidio , Stefano Falone , Carla Tatone","doi":"10.1016/j.arr.2024.102522","DOIUrl":"10.1016/j.arr.2024.102522","url":null,"abstract":"<div><div>Mitochondria are metabolic and signalling hubs that integrate a plethora of interconnected processes to maintain cell homeostasis. They are also dormant mediators of inflammation and cell death, and with aging damages affecting mitochondria gradually accumulate, resulting in the manifestation of age-associated disorders. In addition to coordinate multiple intracellular functions, mitochondria mediate intercellular and inter-organ cross talk in different physiological and stress conditions. To fulfil this task, mitochondrial signalling has evolved distinct and complex conventional and unconventional routes of horizontal/vertical mitochondrial transfer. In this regard, great interest has been focused on the ability of extracellular vesicles (EVs), such as exosomes and microvesicles, to carry selected mitochondrial cargoes to target cells, in response to internal and external cues. Over the past years, the field of mitochondrial EVs (mitoEVs) has grown exponentially, revealing unexpected heterogeneity of these structures associated with an ever-expanding mitochondrial function, though the full extent of the underlying mechanisms is far from being elucidated. Therefore, emerging subsets of EVs encompass exophers, migrasomes, mitophers, mitovesicles, and mitolysosomes that can act locally or over long-distances to restore mitochondrial homeostasis and cell functionality, or to amplify disease. This review provides a comprehensive overview of our current understanding of the biology and trafficking of MitoEVs in different physiological and pathological conditions. Additionally, a specific focus on the role of mitoEVs in aging and the onset and progression of different age-related diseases is discussed.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102522"},"PeriodicalIF":12.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382716","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}
Physical frailty, an age-related decline in the physiological capacity and function of various organs, is associated with higher vulnerability to unfavorable health outcomes. The mechanisms proposed for physical frailty including increased inflammation and oxidative stress are closely related to nutritional status. In addition to traditional nutritional factors such as protein malnutrition and nutrient deficiencies, emerging evidence has focused on the role of functional nutrients including polyphenols, carotenoids, probiotics, prebiotics, omega-3 long-chain polyunsaturated fatty acids (n-3 PUFAs), β-hydroxy-β-methylbutyrate (HMB), coenzyme Q10 (CoQ10), and L-carnitine in modifying the risk of physical frailty syndrome. Although several clinical trials have suggested the beneficial effects of supplementation with polyphenols, HMB, and prebiotics on frailty indices, the current evidence is still not robust to support recommendations on the routine clinical use of such functional nutrients for the management of frailty. Similarly, the association between CoQ10 and frailty was mainly assessed in observational studies, and more randomized controlled trials are needed in this regard. A limited number of studies have reported the beneficial effect of L-carnitine supplementation on frailty indices. Since carnitine is mainly found in skeletal muscle and its measurement is thus challenging due to ethical constraints, it is necessary to examine the effect of different doses of L-carnitine on frailty and its indices in future studies. A large number of interventional studies evaluated the impact of n-3 PUFA supplementation on physical frailty in the elderly and many of them reported improved physical performance following supplementation, especially when combined with resistance training programs. Although promising findings from experimental and observational studies have been reported on functional nutrients, high-quality evidence from randomized controlled trials as well as detailed mechanistic studies are still required to affirm their role in the prevention and/or treatment of physical frailty. This review aims to describe the current state of research on functional nutrients that may modify the development or prognosis of frailty syndrome.
{"title":"Nutritional factors and physical frailty: Highlighting the role of functional nutrients in the prevention and treatment","authors":"Rahele Ziaei , Farnaz Shahdadian , Mohammad Bagherniya , Sercan Karav , Amirhossein Sahebkar","doi":"10.1016/j.arr.2024.102532","DOIUrl":"10.1016/j.arr.2024.102532","url":null,"abstract":"<div><div>Physical frailty, an age-related decline in the physiological capacity and function of various organs, is associated with higher vulnerability to unfavorable health outcomes. The mechanisms proposed for physical frailty including increased inflammation and oxidative stress are closely related to nutritional status. In addition to traditional nutritional factors such as protein malnutrition and nutrient deficiencies, emerging evidence has focused on the role of functional nutrients including polyphenols, carotenoids, probiotics, prebiotics, omega-3 long-chain polyunsaturated fatty acids (n-3 PUFAs), β-hydroxy-β-methylbutyrate (HMB), coenzyme Q10 (CoQ10), and L-carnitine in modifying the risk of physical frailty syndrome. Although several clinical trials have suggested the beneficial effects of supplementation with polyphenols, HMB, and prebiotics on frailty indices, the current evidence is still not robust to support recommendations on the routine clinical use of such functional nutrients for the management of frailty. Similarly, the association between CoQ10 and frailty was mainly assessed in observational studies, and more randomized controlled trials are needed in this regard. A limited number of studies have reported the beneficial effect of L-carnitine supplementation on frailty indices. Since carnitine is mainly found in skeletal muscle and its measurement is thus challenging due to ethical constraints, it is necessary to examine the effect of different doses of L-carnitine on frailty and its indices in future studies. A large number of interventional studies evaluated the impact of n-3 PUFA supplementation on physical frailty in the elderly and many of them reported improved physical performance following supplementation, especially when combined with resistance training programs. Although promising findings from experimental and observational studies have been reported on functional nutrients, high-quality evidence from randomized controlled trials as well as detailed mechanistic studies are still required to affirm their role in the prevention and/or treatment of physical frailty. This review aims to describe the current state of research on functional nutrients that may modify the development or prognosis of frailty syndrome.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102532"},"PeriodicalIF":12.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1016/j.arr.2024.102523
Masoud Rahmati , Lee Smith , Hyeri Lee , Laurent Boyer , Guillaume Fond , Dong Keon Yon , Hayeon Lee , Pinar Soysal , Raphael Udeh , Xenia Dolja-Gore , Mark McEVoy , Mapa Prabhath Piyasena , Shahina Pardhan
Vision impairment (VI) and eye diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and cataract have been reported to be associated with cognitive impairment and dementia, however, to date, very little attempt has been made to collate and synthesizes such literature. Therefore, the aim of this umbrella review is to systematically assesses the credibility and certainty of evidence of associations between vision impairment (VI) and eye diseases with cognitive impairment, dementia and dementia subtypes. We conducted an umbrella review of meta-analyses by screening articles in any language in PubMed, MEDLINE (Ovid), EMBASE, Web of Science, Cochrane CENTRAL and CDSR published from database inception up to May 30, 2024. Quality appraisal of each included original meta-analysis was assessed using A Measurement Tool for Assessing Systematic Reviews 2 (AMSTAR2). The certainty of the evidence was based on statistical significance, study size, heterogeneity, small study effects, prediction intervals (PI), and bias. We followed an a-priori protocol registered with PROSPERO (CRD42024564249). We identified 13 meta-analyses (AMSTAR 2; high accuracy of the findings 1, moderate 10, and low 2) that included 232 original articles based on 99,337,354 participants. Overall, no evidence was highly suggestive or convincing. Suggestive evidence was found for associations between cataract and dementia (equivalent odds ratio [eOR] 1.20, 95 %CI, 1.16–1.25), cataract and Alzheimer’s disease (eOR 1.21, 95 %CI, 1.15–1.28), and AMD and Alzheimer’s disease (eOR 1.27, 95 %CI, 1.27–1.27). Weak evidence was found for associations between VI and dementia (eOR 1.50, 95 %CI, 1.23–1.84), DR and dementia (eOR 1.33, 95 %CI, 1.17–1.50), cataract and vascular dementia (eOR 1.26, 95 %CI, 1.09–1.45), VI identified by cross-sectional studies and cognitive impairment (eOR 2.37, 95 %CI, 2.31–2.44), and VI identified by objective measures and cognitive impairment (eOR 1.56, 95 %CI, 1.12–2.18). The observed suggestive level of evidence for the relationship between eye disease and dementia (as well as dementia subtypes) suggests that policy and interventions to aid in the prevention and management of eye disease may also aid in the prevention of dementia syndrome. Where the level of evidence is weak, further studies are needed with stronger methodological approaches.
{"title":"Associations between vision impairment and eye diseases with dementia, dementia subtypes and cognitive impairment: An umbrella review","authors":"Masoud Rahmati , Lee Smith , Hyeri Lee , Laurent Boyer , Guillaume Fond , Dong Keon Yon , Hayeon Lee , Pinar Soysal , Raphael Udeh , Xenia Dolja-Gore , Mark McEVoy , Mapa Prabhath Piyasena , Shahina Pardhan","doi":"10.1016/j.arr.2024.102523","DOIUrl":"10.1016/j.arr.2024.102523","url":null,"abstract":"<div><div>Vision impairment (VI) and eye diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and cataract have been reported to be associated with cognitive impairment and dementia, however, to date, very little attempt has been made to collate and synthesizes such literature. Therefore, the aim of this umbrella review is to systematically assesses the credibility and certainty of evidence of associations between vision impairment (VI) and eye diseases with cognitive impairment, dementia and dementia subtypes. We conducted an umbrella review of meta-analyses by screening articles in any language in PubMed, MEDLINE (Ovid), EMBASE, Web of Science, Cochrane CENTRAL and CDSR published from database inception up to May 30, 2024. Quality appraisal of each included original meta-analysis was assessed using A Measurement Tool for Assessing Systematic Reviews 2 (AMSTAR2). The certainty of the evidence was based on statistical significance, study size, heterogeneity, small study effects, prediction intervals (PI), and bias. We followed an a-priori protocol registered with PROSPERO (CRD42024564249). We identified 13 meta-analyses (AMSTAR 2; high accuracy of the findings 1, moderate 10, and low 2) that included 232 original articles based on 99,337,354 participants. Overall, no evidence was highly suggestive or convincing. Suggestive evidence was found for associations between cataract and dementia (equivalent odds ratio [eOR] 1.20, 95 %CI, 1.16–1.25), cataract and Alzheimer’s disease (eOR 1.21, 95 %CI, 1.15–1.28), and AMD and Alzheimer’s disease (eOR 1.27, 95 %CI, 1.27–1.27). Weak evidence was found for associations between VI and dementia (eOR 1.50, 95 %CI, 1.23–1.84), DR and dementia (eOR 1.33, 95 %CI, 1.17–1.50), cataract and vascular dementia (eOR 1.26, 95 %CI, 1.09–1.45), VI identified by cross-sectional studies and cognitive impairment (eOR 2.37, 95 %CI, 2.31–2.44), and VI identified by objective measures and cognitive impairment (eOR 1.56, 95 %CI, 1.12–2.18). The observed suggestive level of evidence for the relationship between eye disease and dementia (as well as dementia subtypes) suggests that policy and interventions to aid in the prevention and management of eye disease may also aid in the prevention of dementia syndrome. Where the level of evidence is weak, further studies are needed with stronger methodological approaches.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102523"},"PeriodicalIF":12.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382714","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}
Pub Date : 2024-10-05DOI: 10.1016/j.arr.2024.102524
Karina A. Cicali , Cheril Tapia-Rojas
Aging is a multifaceted biological process characterized by progressive molecular and cellular damage accumulation. The brain hippocampus undergoes functional deterioration with age, caused by cellular deficits, decreased synaptic communication, and neuronal death, ultimately leading to memory impairment. One of the factors contributing to this dysfunction is the loss of mitochondrial function. In neurons, mitochondria are categorized into synaptic and non-synaptic pools based on their location. Synaptic mitochondria, situated at the synapses, play a crucial role in maintaining neuronal function and synaptic plasticity, whereas non-synaptic mitochondria are distributed throughout other neuronal compartments, supporting overall cellular metabolism and energy supply. The proper function of synaptic mitochondria is essential for synaptic transmission as they provide the energy required and regulate calcium homeostasis at the communication sites between neurons. Maintaining the structure and functionality of synaptic mitochondria involves intricate processes, including mitochondrial dynamics such as fission, fusion, transport, and quality control mechanisms. These processes ensure that mitochondria remain functional, replace damaged organelles, and sustain cellular homeostasis at synapses. Notably, deficiencies in these mechanisms have been increasingly associated with aging and the onset of age-related neurodegenerative diseases. Synaptic mitochondria from the hippocampus are particularly vulnerable to age-related changes, including alterations in morphology and a decline in functionality, which significantly contribute to decreased synaptic activity during aging. This review comprehensively explores the critical roles that mitochondrial dynamics and quality control mechanisms play in preserving synaptic activity and neuronal function. It emphasizes the emerging evidence linking the deterioration of synaptic mitochondria to the aging process and the development of neurodegenerative diseases, highlighting the importance of these organelles from hippocampal neurons as potential therapeutic targets for mitigating cognitive decline and synaptic degeneration associated with aging. The novelty of this review lies in its focus on the unique vulnerability of hippocampal synaptic mitochondria to aging, underscoring their importance in maintaining brain function across the lifespan.
{"title":"Synaptic mitochondria: A crucial factor in the aged hippocampus","authors":"Karina A. Cicali , Cheril Tapia-Rojas","doi":"10.1016/j.arr.2024.102524","DOIUrl":"10.1016/j.arr.2024.102524","url":null,"abstract":"<div><div>Aging is a multifaceted biological process characterized by progressive molecular and cellular damage accumulation. The brain hippocampus undergoes functional deterioration with age, caused by cellular deficits, decreased synaptic communication, and neuronal death, ultimately leading to memory impairment. One of the factors contributing to this dysfunction is the loss of mitochondrial function. In neurons, mitochondria are categorized into synaptic and non-synaptic pools based on their location. Synaptic mitochondria, situated at the synapses, play a crucial role in maintaining neuronal function and synaptic plasticity, whereas non-synaptic mitochondria are distributed throughout other neuronal compartments, supporting overall cellular metabolism and energy supply. The proper function of synaptic mitochondria is essential for synaptic transmission as they provide the energy required and regulate calcium homeostasis at the communication sites between neurons. Maintaining the structure and functionality of synaptic mitochondria involves intricate processes, including mitochondrial dynamics such as fission, fusion, transport, and quality control mechanisms. These processes ensure that mitochondria remain functional, replace damaged organelles, and sustain cellular homeostasis at synapses. Notably, deficiencies in these mechanisms have been increasingly associated with aging and the onset of age-related neurodegenerative diseases. Synaptic mitochondria from the hippocampus are particularly vulnerable to age-related changes, including alterations in morphology and a decline in functionality, which significantly contribute to decreased synaptic activity during aging. This review comprehensively explores the critical roles that mitochondrial dynamics and quality control mechanisms play in preserving synaptic activity and neuronal function. It emphasizes the emerging evidence linking the deterioration of synaptic mitochondria to the aging process and the development of neurodegenerative diseases, highlighting the importance of these organelles from hippocampal neurons as potential therapeutic targets for mitigating cognitive decline and synaptic degeneration associated with aging. The novelty of this review lies in its focus on the unique vulnerability of hippocampal synaptic mitochondria to aging, underscoring their importance in maintaining brain function across the lifespan.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102524"},"PeriodicalIF":12.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 10.1016/j.arr.2024.102526
Yanfang Hong, Zuguo Tian, Zhenfeng Ji, Jia Yang, Chaochao Wang
Background
Age-related cognitive decline is a pervasive problem in the aging population. Daoyin therapy is a mind-body movement characteristic of traditional Chinese medicine (TCM). Increasing evidence has reported its usefulness in improving cognitive function among different populations. However, there is no systematic review to assess the effect and mechanism of Daoyin therapy on mild cognitive dysfunction (MCI) in older adults.
Objective
To systematically review the evidence on the effect and mechanism of Daoyin therapy on MCI in older adults.
Results
Taichi, Baduanjin, and Yijinjing can improve cognitive function. Qigong and Wuqinxi can enhance the physical and cognitive functions related to balance, muscle strength, physical endurance, postural control, and flexibility. Taichi, Baduanjin, and Wuqinxi can improve the cognitive function of older adults and alleviate the symptoms associated with MCI through multiple mechanisms. The underlying mechanisms include activating the expression of signals and changing their connections in different brain regions, increasing brain capacity, and regulating brain-derived neurotropic and inflammatory factors.
Conclusion
In summary, the existing evidence from RCTs suggests that traditional Daoyin therapy, such as Taichi, Baduanjin, and Wuqinxi, is a promising strategy that can improve cognitive function and delay the onset of dementia in older adults with MCI by altering structural and neural activities and modulating other factors.
{"title":"A systematic review of the effect and mechanism of Daoyin therapy on improving mild cognitive impairment in older adults","authors":"Yanfang Hong, Zuguo Tian, Zhenfeng Ji, Jia Yang, Chaochao Wang","doi":"10.1016/j.arr.2024.102526","DOIUrl":"10.1016/j.arr.2024.102526","url":null,"abstract":"<div><h3>Background</h3><div>Age-related cognitive decline is a pervasive problem in the aging population. Daoyin therapy is a mind-body movement characteristic of traditional Chinese medicine (TCM). Increasing evidence has reported its usefulness in improving cognitive function among different populations. However, there is no systematic review to assess the effect and mechanism of Daoyin therapy on mild cognitive dysfunction (MCI) in older adults.</div></div><div><h3>Objective</h3><div>To systematically review the evidence on the effect and mechanism of Daoyin therapy on MCI in older adults.</div></div><div><h3>Results</h3><div>Taichi, Baduanjin, and Yijinjing can improve cognitive function. Qigong and Wuqinxi can enhance the physical and cognitive functions related to balance, muscle strength, physical endurance, postural control, and flexibility. Taichi, Baduanjin, and Wuqinxi can improve the cognitive function of older adults and alleviate the symptoms associated with MCI through multiple mechanisms. The underlying mechanisms include activating the expression of signals and changing their connections in different brain regions, increasing brain capacity, and regulating brain-derived neurotropic and inflammatory factors.</div></div><div><h3>Conclusion</h3><div>In summary, the existing evidence from RCTs suggests that traditional Daoyin therapy, such as Taichi, Baduanjin, and Wuqinxi, is a promising strategy that can improve cognitive function and delay the onset of dementia in older adults with MCI by altering structural and neural activities and modulating other factors.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102526"},"PeriodicalIF":12.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378677","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}
Pub Date : 2024-10-03DOI: 10.1016/j.arr.2024.102525
Collin J.C. Exmann , Eline C.M. Kooijmans , Karlijn J. Joling , George L. Burchell , Emiel O. Hoogendijk , Hein P.J. van Hout
Introduction
As complexity and comorbidities increase with age, the increasing number of community-dwelling older adults poses a challenge to healthcare professionals in making trade-offs between beneficial and harmful treatments, monitoring deteriorating patients and resource allocation. Mortality predictions may help inform these decisions. So far, a systematic overview on the characteristics of currently existing mortality prediction models, is lacking.
Objective
To provide a systematic overview and assessment of mortality prediction models for the community-dwelling older population.
Methods
A systematic search of terms related to predictive modelling and older adults was performed until March 1st, 2024, in four databases. We included studies developing multivariable all-cause mortality prediction models for community-dwelling older adults (aged ≥65 years). Data extraction followed the CHARMS Checklist and Quality assessment was performed with the PROBAST tool.
Results
A total of 22 studies involving 38 unique mortality prediction models were included, of which 14 models were based on a cumulative deficit-based frailty index and 9 on machine learning. C-statistics of the models ranged from 0.60 to 0.93 for all studies versus 0.61–0.78 when a frailty index was used. Eight models reached c-statistics higher than 0.8 and reported calibration. The most used variables in all models were demographics, symptoms, diagnoses and physical functioning. Five studies accounting for eleven models had a high risk of bias.
Conclusion
Some mortality prediction models showed promising results for use in practice and most studies were of sufficient quality. However, more uniform methodology and validation studies are needed for clinical implementation.
{"title":"Mortality prediction models for community-dwelling older adults: A systematic review","authors":"Collin J.C. Exmann , Eline C.M. Kooijmans , Karlijn J. Joling , George L. Burchell , Emiel O. Hoogendijk , Hein P.J. van Hout","doi":"10.1016/j.arr.2024.102525","DOIUrl":"10.1016/j.arr.2024.102525","url":null,"abstract":"<div><h3>Introduction</h3><div>As complexity and comorbidities increase with age, the increasing number of community-dwelling older adults poses a challenge to healthcare professionals in making trade-offs between beneficial and harmful treatments, monitoring deteriorating patients and resource allocation. Mortality predictions may help inform these decisions. So far, a systematic overview on the characteristics of currently existing mortality prediction models, is lacking.</div></div><div><h3>Objective</h3><div>To provide a systematic overview and assessment of mortality prediction models for the community-dwelling older population.</div></div><div><h3>Methods</h3><div>A systematic search of terms related to predictive modelling and older adults was performed until March 1st, 2024, in four databases. We included studies developing multivariable all-cause mortality prediction models for community-dwelling older adults (aged ≥65 years). Data extraction followed the CHARMS Checklist and Quality assessment was performed with the PROBAST tool.</div></div><div><h3>Results</h3><div>A total of 22 studies involving 38 unique mortality prediction models were included, of which 14 models were based on a cumulative deficit-based frailty index and 9 on machine learning. C-statistics of the models ranged from 0.60 to 0.93 for all studies versus 0.61–0.78 when a frailty index was used. Eight models reached c-statistics higher than 0.8 and reported calibration. The most used variables in all models were demographics, symptoms, diagnoses and physical functioning. Five studies accounting for eleven models had a high risk of bias.</div></div><div><h3>Conclusion</h3><div>Some mortality prediction models showed promising results for use in practice and most studies were of sufficient quality. However, more uniform methodology and validation studies are needed for clinical implementation.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102525"},"PeriodicalIF":12.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378678","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}
Pub Date : 2024-10-03DOI: 10.1016/j.arr.2024.102533
Puja Ghosh , Rosaria Anna Fontanella , Lucia Scisciola , Fatemeh Taktaz , Ada Pesapane , Manuela Giovanna Basilicata , Giovanni Tortorella , Giulia Matacchione , Annalisa Capuano , Maria Teresa Vietri , Francesco Selvaggi , Giuseppe Paolisso , Michelangela Barbieri
Obesity is one of the most prevalent and increasing metabolic disorders and is considered one of the twelve risk factors for dementia. Numerous studies have demonstrated that obesity induces pathophysiological changes leading to cognitive decline; however, the underlying molecular mechanisms are yet to be fully elucidated. Various biochemical processes, including chronic inflammation, oxidative stress, insulin resistance, dysregulation of lipid metabolism, disruption of the blood-brain barrier, and the release of adipokines have been reported to contribute to the accumulation of senescent neurons during obesity. These senescent cells dysregulate neuronal health and function by exhibiting a senescence-associated secretory phenotype, inducing neuronal inflammation, deregulating cellular homeostasis, causing mitochondrial dysfunction, and promoting microglial infiltration. These factors act as major risks for the occurrence of neurodegenerative diseases and cognitive decline. This review aims to focus on how obesity upregulates neuronal senescence and explores both pharmacological and non-pharmacological interventions for preventing cognitive impairments, thus offering new insights into potential therapeutic strategies.
{"title":"Obesity-induced neuronal senescence: Unraveling the pathophysiological links","authors":"Puja Ghosh , Rosaria Anna Fontanella , Lucia Scisciola , Fatemeh Taktaz , Ada Pesapane , Manuela Giovanna Basilicata , Giovanni Tortorella , Giulia Matacchione , Annalisa Capuano , Maria Teresa Vietri , Francesco Selvaggi , Giuseppe Paolisso , Michelangela Barbieri","doi":"10.1016/j.arr.2024.102533","DOIUrl":"10.1016/j.arr.2024.102533","url":null,"abstract":"<div><div>Obesity is one of the most prevalent and increasing metabolic disorders and is considered one of the twelve risk factors for dementia. Numerous studies have demonstrated that obesity induces pathophysiological changes leading to cognitive decline; however, the underlying molecular mechanisms are yet to be fully elucidated. Various biochemical processes, including chronic inflammation, oxidative stress, insulin resistance, dysregulation of lipid metabolism, disruption of the blood-brain barrier, and the release of adipokines have been reported to contribute to the accumulation of senescent neurons during obesity. These senescent cells dysregulate neuronal health and function by exhibiting a senescence-associated secretory phenotype, inducing neuronal inflammation, deregulating cellular homeostasis, causing mitochondrial dysfunction, and promoting microglial infiltration. These factors act as major risks for the occurrence of neurodegenerative diseases and cognitive decline. This review aims to focus on how obesity upregulates neuronal senescence and explores both pharmacological and non-pharmacological interventions for preventing cognitive impairments, thus offering new insights into potential therapeutic strategies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102533"},"PeriodicalIF":12.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1016/j.arr.2024.102528
Fei Zhang , Ying Yan , Chunlin Ge
Background
Frailty is the most problematic expression of population ageing, which has been associated with increased mortality and complications among patients with gastric cancer (GC). However, previous evidence about the frailty prevalence and outcomes in frail populations with gastric cancer remains unknown.
Methods
Eligible studies were searched in Embase, PubMed, Scopus, and Web of Science to explore the prevalence and impact of frailty in patients with gastric cancer from inception until November 25, 2023. The pooled prevalence of frailty, hazard ratio (HR), and odds ratio (OR) corresponding 95 % confidence intervals (CI) in mortality and postoperative complications estimates were analyzed.
Results
A total of 24 studies containing 75,357 GC patients were involved. The prevalence of frailty in gastric cancer was 27 % (95 % CI = 24–30; I2 = 96.7 %; p = 0.000). Frailty was independently associated with an increased hazard ratio for mortality (adjusted HR = 2.14; 95 % CI = 1.60–2.86; I2 = 67.3 %, p = 0.000). Furthermore, frailty was significantly associated with an increased odds ratio for postoperative complication in GC patients (adjusted OR = 2.65; 95 % CI = 2.17–3.25; I2 = 0.0 %, Cochran’s Q = 1.20, p = 0.878).
Conclusion
The prevalence of frailty in gastric cancer is common and has a significant adverse effect on GC patients’ outcomes. Our findings highlight the importance of routine frailty assessment in GC patients, which may provide prognostic outcomes.
背景：虚弱是人口老龄化最棘手的表现形式，它与胃癌（GC）患者死亡率和并发症的增加有关。然而，以往关于胃癌患者中体弱人群的虚弱发生率和结局的证据仍然未知：在 Embase、PubMed、Scopus 和 Web of Science 中检索了符合条件的研究，以探讨胃癌患者自发病至 2023 年 11 月 25 日期间的虚弱患病率及其影响。分析了死亡率和术后并发症估算中的合并虚弱患病率、危险比（HR）和相应的95%置信区间（CI）的几率比（OR）：结果：共有 24 项研究涉及 75,357 名胃癌患者。胃癌患者体弱的发生率为 27% (95% CI = 24-30; I2 = 96.7%; p = 0.000)。虚弱与死亡率危险比的增加密切相关（调整后 HR = 2.14；95% CI = 1.60-2.86；I2 = 67.3%，p = 0.000）。此外，体弱与胃癌患者术后并发症的几率增加有明显关系（调整后 OR = 2.65；95% CI = 2.17-3.25；I2 = 0.0%，Cochran's Q = 1.20，p = 0.878）：胃癌患者普遍体弱，这对胃癌患者的预后有显著的不利影响。我们的研究结果凸显了对胃癌患者进行常规虚弱评估的重要性，它可提供预后结果。
{"title":"Frailty as a predictor of adverse outcomes in patients with gastric cancer: A systematic review and meta-analysis of 75,357 patients","authors":"Fei Zhang , Ying Yan , Chunlin Ge","doi":"10.1016/j.arr.2024.102528","DOIUrl":"10.1016/j.arr.2024.102528","url":null,"abstract":"<div><h3>Background</h3><div>Frailty is the most problematic expression of population ageing, which has been associated with increased mortality and complications among patients with gastric cancer (GC). However, previous evidence about the frailty prevalence and outcomes in frail populations with gastric cancer remains unknown.</div></div><div><h3>Methods</h3><div>Eligible studies were searched in Embase, PubMed, Scopus, and Web of Science to explore the prevalence and impact of frailty in patients with gastric cancer from inception until November 25, 2023. The pooled prevalence of frailty, hazard ratio (HR), and odds ratio (OR) corresponding 95 % confidence intervals (CI) in mortality and postoperative complications estimates were analyzed.</div></div><div><h3>Results</h3><div>A total of 24 studies containing 75,357 GC patients were involved. The prevalence of frailty in gastric cancer was 27 % (95 % CI = 24–30; I<sup>2</sup> = 96.7 %; <em>p</em> = 0.000). Frailty was independently associated with an increased hazard ratio for mortality (adjusted HR = 2.14; 95 % CI = 1.60–2.86; I<sup>2</sup> = 67.3 %, <em>p</em> = 0.000). Furthermore, frailty was significantly associated with an increased odds ratio for postoperative complication in GC patients (adjusted OR = 2.65; 95 % CI = 2.17–3.25; I<sup>2</sup> = 0.0 %, Cochran’s Q = 1.20, <em>p</em> = 0.878).</div></div><div><h3>Conclusion</h3><div>The prevalence of frailty in gastric cancer is common and has a significant adverse effect on GC patients’ outcomes. Our findings highlight the importance of routine frailty assessment in GC patients, which may provide prognostic outcomes.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102528"},"PeriodicalIF":12.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1016/j.arr.2024.102519
Azhagu Madhavan Sivalingam
Cerebellar dysfunction is increasingly recognized as a critical factor in various neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Research has revealed distinct cerebellar atrophy patterns in conditions such as AD and multiple system atrophy, and studies in mice have highlighted its impact on motor control and cognitive functions. Emerging research into autism spectrum disorder (ASD) has identified key targets, such as elevated levels of chemokine receptors and ZIC family genes. Biomarkers, including cerebrospinal fluid (CSF), genetic markers, and advances in AI and bioinformatics, are enhancing early diagnosis and personalized treatment across neurodegenerative disorders. Notable advancements include improved diagnostic tools, gene therapy, and novel clinical trials. Despite progress, challenges such as the bloodbrain barrier and neuroinflammation persist. Current therapies for AD, PD, HD, and ALS, including antisense oligonucleotides and stem cell treatments, show promise but require further investigation. A comprehensive approach that integrates diagnostic methods and innovative therapies is essential for effective management and improved patient outcomes.
{"title":"Advances in understanding biomarkers and treating neurological diseases – Role of the cerebellar dysfunction and emerging therapies","authors":"Azhagu Madhavan Sivalingam","doi":"10.1016/j.arr.2024.102519","DOIUrl":"10.1016/j.arr.2024.102519","url":null,"abstract":"<div><div>Cerebellar dysfunction is increasingly recognized as a critical factor in various neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Research has revealed distinct cerebellar atrophy patterns in conditions such as AD and multiple system atrophy, and studies in mice have highlighted its impact on motor control and cognitive functions. Emerging research into autism spectrum disorder (ASD) has identified key targets, such as elevated levels of chemokine receptors and ZIC family genes. Biomarkers, including cerebrospinal fluid (CSF), genetic markers, and advances in AI and bioinformatics, are enhancing early diagnosis and personalized treatment across neurodegenerative disorders. Notable advancements include improved diagnostic tools, gene therapy, and novel clinical trials. Despite progress, challenges such as the blood<img>brain barrier and neuroinflammation persist. Current therapies for AD, PD, HD, and ALS, including antisense oligonucleotides and stem cell treatments, show promise but require further investigation. A comprehensive approach that integrates diagnostic methods and innovative therapies is essential for effective management and improved patient outcomes.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102519"},"PeriodicalIF":12.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1016/j.arr.2024.102521
Fabiola Olivieri , Leonardo Biscetti , Lorenzo Pimpini , Giuseppe Pelliccioni , Jacopo Sabbatinelli , Sergio Giunta
The most cutting-edge issue in the research on aging is the quest for biomarkers that transcend molecular and cellular domains to encompass organismal-level implications. We recently hypothesized the role of Autonomic Nervous System (ANS) imbalance in this context. Studies on ANS functions during aging highlighted an imbalance towards heightened sympathetic nervous system (SNS) activity, instigating a proinflammatory milieu, and attenuated parasympathetic nervous system (PNS) function, which exerts anti-inflammatory effects via the cholinergic anti-inflammatory pathway (CAP) and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. This scenario strongly suggests that ANS imbalance can fuel inflammaging, now recognized as one of the most relevant risk factors for age-related disease development. Recent recommendations have increasingly highlighted the need for actionable strategies to improve the quality of life for older adults by identifying biomarkers that can be easily measured, even in asymptomatic individuals. We advocate for considering ANS imbalance as a biomarker of aging and inflammaging. Measures of ANS imbalance, such as heart rate variability (HRV), are relatively affordable, non-invasive, and cost-effective, making this hallmark easily diagnosable. HRV gains renewed significance within the aging research landscape, offering a tangible link between pathophysiological perturbations and age-related health outcomes.
{"title":"Heart rate variability and autonomic nervous system imbalance: Potential biomarkers and detectable hallmarks of aging and inflammaging","authors":"Fabiola Olivieri , Leonardo Biscetti , Lorenzo Pimpini , Giuseppe Pelliccioni , Jacopo Sabbatinelli , Sergio Giunta","doi":"10.1016/j.arr.2024.102521","DOIUrl":"10.1016/j.arr.2024.102521","url":null,"abstract":"<div><div>The most cutting-edge issue in the research on aging is the quest for biomarkers that transcend molecular and cellular domains to encompass organismal-level implications. We recently hypothesized the role of Autonomic Nervous System (ANS) imbalance in this context. Studies on ANS functions during aging highlighted an imbalance towards heightened sympathetic nervous system (SNS) activity, instigating a proinflammatory milieu, and attenuated parasympathetic nervous system (PNS) function, which exerts anti-inflammatory effects via the cholinergic anti-inflammatory pathway (CAP) and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. This scenario strongly suggests that ANS imbalance can fuel inflammaging, now recognized as one of the most relevant risk factors for age-related disease development. Recent recommendations have increasingly highlighted the need for actionable strategies to improve the quality of life for older adults by identifying biomarkers that can be easily measured, even in asymptomatic individuals. We advocate for considering ANS imbalance as a biomarker of aging and inflammaging. Measures of ANS imbalance, such as heart rate variability (HRV), are relatively affordable, non-invasive, and cost-effective, making this hallmark easily diagnosable. HRV gains renewed significance within the aging research landscape, offering a tangible link between pathophysiological perturbations and age-related health outcomes.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102521"},"PeriodicalIF":12.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334146","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}
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