Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mo...Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable.展开更多
SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, tha...SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major coh...Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.展开更多
Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence ...Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.展开更多
Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provid...Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provides intercellular metabolic support to axons.Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases.In fact,myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases,including multiple sclerosis and Alzheimer’s disease.In the central nervous system,compact myelin sheaths are formed by fully mature oligodendrocytes.However,the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages.In addition to their well-known role in action potential propagation,oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes.Therefore,myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases.Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals.In this review,we investigate the changes in myelin that are associated with aging and their underlying mechanisms.We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent,slow down,or even reverse age-related myelin degeneration.Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.展开更多
The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurode...The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.展开更多
文摘Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable.
基金supported by Science Foundation Ireland (Grant 19/FFP/6666),Cure Parkinson’s (Grant CP:GO01)a PhD studentship from the Anatomical Society。
文摘SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
文摘Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.
文摘Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.
基金supported by grants from Guangdong Basic and Applied Basic Research Foundation,No.2021A1515110801(to SW)the National Natural Science Foundation of China,No.82301511(to SW)+1 种基金“Double First-Class”Construction Project of NPU,Nos.0515023GH0202320(to JC),0515023SH0201320(to JC)973 Program,No.2011CB504100(to JC).
文摘Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provides intercellular metabolic support to axons.Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases.In fact,myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases,including multiple sclerosis and Alzheimer’s disease.In the central nervous system,compact myelin sheaths are formed by fully mature oligodendrocytes.However,the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages.In addition to their well-known role in action potential propagation,oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes.Therefore,myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases.Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals.In this review,we investigate the changes in myelin that are associated with aging and their underlying mechanisms.We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent,slow down,or even reverse age-related myelin degeneration.Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.
文摘The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.
