Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even...The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.展开更多
The advancement of Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)gene editing technology has revolutionized the comprehension of human genome,propelling molecular and cellular biology research into ...The advancement of Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)gene editing technology has revolutionized the comprehension of human genome,propelling molecular and cellular biology research into unexplored realms and accelerating progress in life sciences and medicine.CRISPR-based gene screening,recognized for its efficiency and practicality,is widely utilized across diverse biological fields.Aging is a multifaceted process governed by a myriad of genetic and epigenetic factors.Unraveling the genes regulating aging holds promise for understanding this intricate phenomenon and devising strategies for its assessment and intervention.This review provides a comprehensive overview of the progress in CRISPR screening and its applications in aging research,while also offering insights into future directions.CRISPR-based genetic-manipulation tools are positioned as indispensable instruments for mitigating aging and managing age-related diseases.展开更多
As the life expectancy of the world’s population increases,age-related diseases are emerging as one of the greatest problems facing modern society.The onset of dementia and neurodegenerative diseases is strictly depe...As the life expectancy of the world’s population increases,age-related diseases are emerging as one of the greatest problems facing modern society.The onset of dementia and neurodegenerative diseases is strictly dependent on aging as a major risk factor and has a profound impact on various aspects of the lives of individuals and their families.展开更多
Melatonin(N-acetyl-5-methoxytryptamine)is known as the hormone of darkness because it is synthesized at night and involved in regulating the circadian clock.The hormone is primarily synthesized by the vertebrate pinea...Melatonin(N-acetyl-5-methoxytryptamine)is known as the hormone of darkness because it is synthesized at night and involved in regulating the circadian clock.The hormone is primarily synthesized by the vertebrate pineal gland,but is ubiquitous among invertebrates,unicellular organisms,plants,and even cyanobacteria(Hattori and Suzuki,2024).Melatonin is well-conserved evolutionarily and possesses several physiological functions,such as immune response,bone and glucose metabolism,and memory formation besides regulating the circadian rhythm.展开更多
Poor bone quality is a major factor in skeletal fragility in elderly individuals.The molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily d...Poor bone quality is a major factor in skeletal fragility in elderly individuals.The molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by osteocytes.We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material properties.We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses PLR.The control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)bone.This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests.The effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.展开更多
The aging population has far-reaching implications for health,significantly influencing medical care and health policy.According to the World Health Organization(WHO),by 2030,one in six people worldwide will be aged 6...The aging population has far-reaching implications for health,significantly influencing medical care and health policy.According to the World Health Organization(WHO),by 2030,one in six people worldwide will be aged 60 years or older.Furthermore,the population of individuals aged 60 and older is projected to increase from 1 billion in 2020 to 1.4 billion in 2030.By 2050,this population is expected to double,reaching 2.1 billion.Similarly,the number of people aged 80 years and older is anticipated to triple between 2020 and 2050,reaching 426 million[1].This demographic shift toward older adults,known as population aging,initially began in high-income countries but has now extended to low and middle-income nations.By 2050,approximately two-thirds of the world’s population aged 60 and older will reside in these countries.The effects of this aging population pose significant challenges for human health,necessitating substantial societal adjustments[2].展开更多
Aging is a process characterized by accumulating degenerative damages,resulting in the death of an organism ultimately.The main goal of aging research is to develop therapies that delay age-related diseases in human.S...Aging is a process characterized by accumulating degenerative damages,resulting in the death of an organism ultimately.The main goal of aging research is to develop therapies that delay age-related diseases in human.Since signaling pathways in aging of Caenorhabditis elegans(C.elegans),fruit flies and mice are evolutionarily conserved,compounds extending lifespan of them by intervening pathways of aging may be useful in treating age-related diseases in human.Natural products have special resource advantage and with few side effect.Recently,many compounds or extracts from natural products slowing aging and extending lifespan have been reported.Here we summarized these compounds or extracts and their mechanisms in increasing longevity of C.elegans or other species,and the prospect in developing antiaging medicine from natural products.展开更多
In the aging brain, cognitive function gradually dedines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel ne...In the aging brain, cognitive function gradually dedines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (〈1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.展开更多
During normal aging,there is a decline in all physiological functions in the organism.One of the most affected organs is the brain,where neurons lose their proper synaptic function leading to cognitive impairment.Agin...During normal aging,there is a decline in all physiological functions in the organism.One of the most affected organs is the brain,where neurons lose their proper synaptic function leading to cognitive impairment.Aging is one of the main risk factors for the development of neurodegenerative diseases,such as Alzheimer’s disease.One of the main responsible factors for synaptic dysfunction in aging and neurodegenerative diseases is the accumulation of abnormal proteins forming aggregates.The most studied brain aggregates are the senile plaques,formed by Aβpeptide;however,the aggregates formed by phosphorylated tau protein have gained relevance in the last years by their toxicity.It is reported that neurons undergo severe mitochondrial dysfunction with age,with a decrease in adenosine 5′-triphosphate production,loss of the mitochondrial membrane potential,redox imbalance,impaired mitophagy,and loss of calcium buffer capacity.Interestingly,abnormal tau protein interacts with several mitochondrial proteins,suggesting that it could induce mitochondrial dysfunction.Nevertheless,whether tau-mediated mitochondrial dysfunction occurs indirectly or directly is still unknown.A recent study of our laboratory shows that phosphorylated tau at Ser396/404(known as PHF-1),an epitope commonly related to pathology,accumulates inside mitochondria during normal aging.This accumulation occurs preferentially in synaptic mitochondria,which suggests that it may contribute to the synaptic failure and cognitive impairment seen in aged individuals.Here,we review the main tau modifications promoting mitochondrial dysfunction,and the possible mechanism involved.Also,we discuss the evidence that supports the possibility that phosphorylated tau accumulation in synaptic mitochondria promotes synaptic and cognitive impairment in aging.Finally,we show evidence and argue about the presence of phosphorylated tau PHF-1 inside mitochondria in Alzheimer’s disease,which could be considered as an early event in the neurodegenerative process.Thus,phosphorylated tau PHF-1 inside the mitochondria could be considered such a potential therapeutic target to prevent or attenuate age-related cognitive impairment.展开更多
BACKGROUND:Traumatic aortic dissection(TAD)has a low incidence but extremely high mortality.It always presents atypical clinical manifestations that are easily missed or misdiagnosed.This study mainly aims to describe...BACKGROUND:Traumatic aortic dissection(TAD)has a low incidence but extremely high mortality.It always presents atypical clinical manifestations that are easily missed or misdiagnosed.This study mainly aims to describe the imaging characteristics and management of TAD patients.METHODS:A retrospective analysis of 27 blunt TAD patients was performed between 2013 and 2020.Demographic features,imaging characteristics,and management were analyzed.RESULTS:Twenty-seven patients with type B aortic dissection(age 56.04±16.07 years,20 men)were included.Aortic intimal tears were mostly initiated from the aortic isthmus.The sizes of the proximal intimal tears in the greater curvature were larger than those in the lesser curvature(1.78±0.56 cm vs.1.24±0.52 cm,P=0.031).Compared with those in the control group,the maximum diameters of the aortic arch,thoracic aorta,and abdominal aorta in the TAD patients were all significantly widened(all P<0.050).Multivariate logistic regression analysis showed that the maximum diameter of the thoracic aorta was an independent risk factor for TAD,with a predictive value with an area under the receiver operating characteristic curve(AUC)of 0.673.Finally,26 patients successfully underwent delayed thoracic endovascular aortic repair(TEVAR),and the remaining one patient was treated conservatively.No progression of aortic dissection or death occurred during the six-month follow-up period.CONCLUSIONS:In blunt trauma,the aortic isthmus is the most common site of proximal intimal tears.An accurate diagnosis of TAD requires an overall consideration of medical history and imaging characteristics.Delayed TEVAR might be an eff ective therapeutic option for TAD.展开更多
In line with the worldwide trend in population aging,China has stepped into an aging society since 2000.The outstanding features of aging,including a large proportion of the older population,rapid growth,dramatic expa...In line with the worldwide trend in population aging,China has stepped into an aging society since 2000.The outstanding features of aging,including a large proportion of the older population,rapid growth,dramatic expansion of the oldest-old,and uneven aging distribution,have put China in a unique position.Besides,older population is expanding in parallel with the escalating burden of disease,high prevalence of disability,and low social involvement.However,China is not prepared to solve these problems in terms of the economy,awareness,geriatric care system,geriatric team,social security,or age-friendly environment.From the perspective of public health,we summarized the major challenges and proposed the following policy recommendations:(1)strengthening the top-level design and building a"government-leading,multi-sectoral-cooperating,and society-participating"pattern;(2)enhancing health services by implementing the"comprehensive health"strategy;(3)developing home and community care,coordinately enhance institutional care,promote integration of medical and care systems,and establish a multidimensional tailored care system;(4)optimizing geriatric the supporting system,included the construction of geriatric team and the long-term care insurance system;and(5)establishing a physical and socially age-friendly environment.展开更多
BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)imaging.However,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions ...BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)imaging.However,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions and healthy tissue.This study was undertaken to evaluate the efficacy and safety of the liverspecific MR imaging contrast agent gadoxetate disodium(GdEOB-DTPA)in Chinese patients.METHODS:This was a single-arm,open-label,multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging.MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA(0.025 mmol/kg body weight).Images were evaluated by clinical study investigators and three independent,blinded radiologists.The primary efficacy endpoint was sensitivity in lesion detection.RESULTS:Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46%compared with pre-contrast imaging for the average of the three blinded readers(94.78%vs 85.32%for Gd-EOB-DTPA vs pre-contrast,respectively).Improvements in detection were more pronounced in lesions less than 1cm.Gd-EOB-DTPA improved diagnostic accuracy in lesion classification.CONCLUSIONS:This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions,particularly in those smaller than 1 cm.Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification,and furthermore,Gd-EOB-DTPA is safe in Chinese patients with liver lesions.展开更多
Fluorescence lifetime is not only associated with the molecular structure f fuorophores,but alsostrongly depends on the environment around them,which llows fuorescence lifetime imagingmicroscopy(FLIM)to be used as a t...Fluorescence lifetime is not only associated with the molecular structure f fuorophores,but alsostrongly depends on the environment around them,which llows fuorescence lifetime imagingmicroscopy(FLIM)to be used as a tool for precise measurement of the cell or tisue microenvironment,This review introduces the basic principle of fuorescence lifetime imagingtechnology and its application in clinical medicine,including research and diagnosis of diseases inskin,brain,eyes,mouth,bone,blood vessels and cavity organs,and drug evaluation.As anoninvasive,nontoxic and nonionizing radiation technique,FLIM demonstrates excellent per-formance with high sensitivity and specificity,which allows to determine precise position of thelesion and,thus,has good potential for application in biomedical research and clinical diagnosis.展开更多
1 Aging in Asia-an avalanche starts to form With decreasing fertilityrate and increasing life expectan-cy, the world is aging- withhighest rates in Asia. The socio-economic, financial and medicalconsequences of the ag...1 Aging in Asia-an avalanche starts to form With decreasing fertilityrate and increasing life expectan-cy, the world is aging- withhighest rates in Asia. The socio-economic, financial and medicalconsequences of the aging popu-展开更多
The degradation of crosslinked polyethylene (XLPE) cable insulation during service, such as thermo-oxidation and water treeing may lead to a premature electrical breakdown of the XLPE insulation cables. Therefore, it ...The degradation of crosslinked polyethylene (XLPE) cable insulation during service, such as thermo-oxidation and water treeing may lead to a premature electrical breakdown of the XLPE insulation cables. Therefore, it is necessary to optimize the period of replacement to evenly distribute the replacement cost by ascertaining the deterioration degree. Estimation of the aging degree is at present the most important task for diagnosis of the residual lifetime of the power cable insulation. This paper presents a study on the changes in the dielectric properties of the thermally aged XLPE cables in the frequency range from 0.07~10 MHz. Based on electrical and physicochemical characterization, some new "dactylograms" for the thermally aged XLPE cable insulation have been proposed.展开更多
The deposition of mineral phases on the heat transfer surfaces of brown coal power plants may have a negative effect on power plant boilers. The paragenesis of these deposits contains information about the actual temp...The deposition of mineral phases on the heat transfer surfaces of brown coal power plants may have a negative effect on power plant boilers. The paragenesis of these deposits contains information about the actual temperature prevailed during the combustion of lignite, if the temperature-dependences of distinct mineral transformations or reactions are known. Here, we report results of a sintering study (to ?1100℃) with samples containing anhydrite, quartz, and gehlenite, which are typical components of Rhenish lignite ashes. Thermal decompositions and solid-state reactions were analyzed (1) in situ and (2) both in situ and after quenching using confocal hyperspectral Raman imaging. This novel application of confocal Raman spectroscopy provides temperature-and time-resolved, 2-dimensional information about sintering processes with a micrometer-scale resolution. In the course of the sintering experiments with anhydrite and quartz with a weight ratio of 2:1 both polymorphs wollastonite and pseudowollastonite were identified in situ at about 920 and 1000℃, respectively. The formation of pseudowollastonite was thus observed about 120℃ below the phase transition temperature, demonstrating that it can form metastably. In addition,α′L-Ca2SiO4 was identified at about 1100℃. In samples containing equal weight fractions of anhydrite and quartz that were quenched after firing for 9h at about 1100℃,β-Ca2SiO4 (larnite) crystallized as rims around anhydrite grains and in direct contact to wollastonite. We furthermore observed that, depending on the ratio between quartz and anhydrite, wollastonite replaced quartz grains between 920 and 1100℃., i.e., the higher the quartz content, the lower the formation temperature of wollastonite.展开更多
AIM: To describe and evaluate a standardized protocol for measuring the choroidal thickness(Ch T) using enhanced depth imaging optical coherence tomography(EDI OCT).METHODS: Single 9 mm EDI OCT line scans across the f...AIM: To describe and evaluate a standardized protocol for measuring the choroidal thickness(Ch T) using enhanced depth imaging optical coherence tomography(EDI OCT).METHODS: Single 9 mm EDI OCT line scans across the fovea were used for this study. The protocol used in this study classified the EDI OCT images into four groups based on the appearance of the choroidal-scleral interface and suprachoroidal space. Two evaluation iterations of experiments were performed: first, the protocol was validated in a pilot study of 12 healthy eyes. Afterwards, the applicability of the protocol was tested in 82 eyes of patients with diabetes. Inter-observer and intra-observer agreements on image classifications were performed using Cohen’s kappa coefficient(κ). Intraclass correlation coefficient(ICC) and Bland-Altman’s methodology were used for the measurement of the Ch T.RESULTS: There was a moderate(κ=0.42) and perfect(κ =1) inter- and intra-observer agreements on image classifications from healthy eyes images and substantial(κ =0.66) and almost perfect(κ =0.86) agreements from diabetic eyes images. The proposed protocol showed excellent inter- and intra-observer agreements for the Ch T measurements on both, healthy eyes and diabetic eyes(ICC 】0.90 in all image categories). The Bland-Altman plot showed a relatively large Ch T measurement agreement in the scans that contained less visible choroidal outer boundary. CONCLUSION: A protocol to standardize Ch T measurements in EDI OCT images has been developed;the results obtained using this protocol show that the technique is accurate and reliable for routine clinical practice and research.展开更多
<strong>Background:</strong> Young and intact skin is highly responsive. As skin ages, its responsiveness decreases. Production of structural components of the skin slows down and signs of skin aging appea...<strong>Background:</strong> Young and intact skin is highly responsive. As skin ages, its responsiveness decreases. Production of structural components of the skin slows down and signs of skin aging appear. External influences like UV radiation and pollution contribute to signs of skin aging. They lead to an increased formation of so-called free radicals. Bioactive antioxidant compounds, such as polyphenols, have beneficial effects on skin health by free radical scavenging. The purpose of this study was to evaluate the topical effects of new and highly concentrated resveratrol containing emulsion (Medskin Solutions Dr. Suwelack AG, 2% trans-resveratrol) on age-related alterations to the skin. <strong>Methods:</strong> A clinical observation study was performed on 20 subjects to observe the effects of a 2% resveratrol emulsion on typical signs of skin aging. Product was applied once daily for a period of 8 weeks in combination with a standardized treatment. Tested parameters were skin elasticity, skin barrier function, skin smoothness, skin thickness and density. <strong>Results:</strong> After 8 weeks of treatment, skin pH value is significantly lowered and skin barrier function improved. The value of skin elasticity (+5.3%), and skin density (+ 10.7%) had increased, while skin roughness (-6.4%) and skin dispensability (-45.9%) had diminished. Intensity of skin redness had decreased. Furthermore, expert and participant evaluations show satisfaction, especially with regard to skin smoothness and skin moisture. Conclusion: The resveratrol emulsion shows positive outcomes by supporting reduction of skin wrinkling and increasing skin firmness, as well as reducing skin redness, and is therefore an all-round anti-aging treatment.展开更多
Aging is a dynamic and progressive process that begins at conception and continues until death.This process leads to a decrease in homeostasis and morphological,biochemical and psychological changes,increasing the ind...Aging is a dynamic and progressive process that begins at conception and continues until death.This process leads to a decrease in homeostasis and morphological,biochemical and psychological changes,increasing the individual’s vulnerability to various diseases.The growth in the number of aging populations has increased the prevalence of chronic degenerative diseases,impairment of the central nervous system and dementias,such as Alzheimer’s disease,whose main risk factor is age,leading to an increase of the number of individuals who need daily support for life activities.Some theories about aging suggest it is caused by an increase of cellular senescence and reactive oxygen species,which leads to inflammation,oxidation,cell membrane damage and consequently neuronal death.Also,mitochondrial mutations,which are generated throughout the aging process,can lead to changes in energy production,deficiencies in electron transport and apoptosis induction that can result in decreased function.Additionally,increasing cellular senescence and the release of proinflammatory cytokines can cause irreversible damage to neuronal cells.Recent reports point to the importance of changing lifestyle by increasing physical exercise,improving nutrition and environmental enrichment to activate neuroprotective defense mechanisms.Therefore,this review aims to address the latest information about the different mechanisms related to neuroplasticity and neuronal death and to provide strategies that can improve neuroprotection and decrease the neurodegeneration caused by aging and environmental stressors.展开更多
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
基金supported by the National Natural Science Foundation of China,No.81921006(to GHL)。
文摘The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.
文摘The advancement of Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)gene editing technology has revolutionized the comprehension of human genome,propelling molecular and cellular biology research into unexplored realms and accelerating progress in life sciences and medicine.CRISPR-based gene screening,recognized for its efficiency and practicality,is widely utilized across diverse biological fields.Aging is a multifaceted process governed by a myriad of genetic and epigenetic factors.Unraveling the genes regulating aging holds promise for understanding this intricate phenomenon and devising strategies for its assessment and intervention.This review provides a comprehensive overview of the progress in CRISPR screening and its applications in aging research,while also offering insights into future directions.CRISPR-based genetic-manipulation tools are positioned as indispensable instruments for mitigating aging and managing age-related diseases.
基金funded by U.S.Air Force Office of Scientific Research,No.FA9550-21-1-0096FONDAP program,No.15150012+1 种基金Department of Defense grant,Nos.W81XWH2110960,ANID/FONDEF ID1ID22I10120,and ANID/NAM22I0057Swiss Consolidation Grant-The Leading House for the Latin American Region(all to CH)。
文摘As the life expectancy of the world’s population increases,age-related diseases are emerging as one of the greatest problems facing modern society.The onset of dementia and neurodegenerative diseases is strictly dependent on aging as a major risk factor and has a profound impact on various aspects of the lives of individuals and their families.
基金supported by JSPS KAKENHI Grant Number JP22K11823 to AH and JP22J01508 to KW。
文摘Melatonin(N-acetyl-5-methoxytryptamine)is known as the hormone of darkness because it is synthesized at night and involved in regulating the circadian clock.The hormone is primarily synthesized by the vertebrate pineal gland,but is ubiquitous among invertebrates,unicellular organisms,plants,and even cyanobacteria(Hattori and Suzuki,2024).Melatonin is well-conserved evolutionarily and possesses several physiological functions,such as immune response,bone and glucose metabolism,and memory formation besides regulating the circadian rhythm.
文摘Poor bone quality is a major factor in skeletal fragility in elderly individuals.The molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by osteocytes.We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material properties.We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses PLR.The control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)bone.This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests.The effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.
文摘The aging population has far-reaching implications for health,significantly influencing medical care and health policy.According to the World Health Organization(WHO),by 2030,one in six people worldwide will be aged 60 years or older.Furthermore,the population of individuals aged 60 and older is projected to increase from 1 billion in 2020 to 1.4 billion in 2030.By 2050,this population is expected to double,reaching 2.1 billion.Similarly,the number of people aged 80 years and older is anticipated to triple between 2020 and 2050,reaching 426 million[1].This demographic shift toward older adults,known as population aging,initially began in high-income countries but has now extended to low and middle-income nations.By 2050,approximately two-thirds of the world’s population aged 60 and older will reside in these countries.The effects of this aging population pose significant challenges for human health,necessitating substantial societal adjustments[2].
基金the Natural Science Foundation of China(81671405 and 81370453)Natural Science Foundation of Yunnan province(2013FA045 and 2015FB172)Open Funds of Guangdong Key Laboratory of Marine Materia Medica.
文摘Aging is a process characterized by accumulating degenerative damages,resulting in the death of an organism ultimately.The main goal of aging research is to develop therapies that delay age-related diseases in human.Since signaling pathways in aging of Caenorhabditis elegans(C.elegans),fruit flies and mice are evolutionarily conserved,compounds extending lifespan of them by intervening pathways of aging may be useful in treating age-related diseases in human.Natural products have special resource advantage and with few side effect.Recently,many compounds or extracts from natural products slowing aging and extending lifespan have been reported.Here we summarized these compounds or extracts and their mechanisms in increasing longevity of C.elegans or other species,and the prospect in developing antiaging medicine from natural products.
基金supported by the Natural Science Foundation of Hebei Province of China,No.H2015206409Science and Technology Research Youth Fund Project of Hebei Colleges and Universities in China,No.QN20131068,QN2014140+1 种基金a grant from Health and Family Planning Commission Medical Scientific Research Project in Hebei Province of China,No.ZL20140017a grant from Hebei Science and Technology Support Program Project of China,No.132777209,132777135
文摘In the aging brain, cognitive function gradually dedines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (〈1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.
基金supported by FONDECYT,No.11170546,CONICYT PAI,No.77170091(to CTR)FONDECYT,No.3210591(to CJ).
文摘During normal aging,there is a decline in all physiological functions in the organism.One of the most affected organs is the brain,where neurons lose their proper synaptic function leading to cognitive impairment.Aging is one of the main risk factors for the development of neurodegenerative diseases,such as Alzheimer’s disease.One of the main responsible factors for synaptic dysfunction in aging and neurodegenerative diseases is the accumulation of abnormal proteins forming aggregates.The most studied brain aggregates are the senile plaques,formed by Aβpeptide;however,the aggregates formed by phosphorylated tau protein have gained relevance in the last years by their toxicity.It is reported that neurons undergo severe mitochondrial dysfunction with age,with a decrease in adenosine 5′-triphosphate production,loss of the mitochondrial membrane potential,redox imbalance,impaired mitophagy,and loss of calcium buffer capacity.Interestingly,abnormal tau protein interacts with several mitochondrial proteins,suggesting that it could induce mitochondrial dysfunction.Nevertheless,whether tau-mediated mitochondrial dysfunction occurs indirectly or directly is still unknown.A recent study of our laboratory shows that phosphorylated tau at Ser396/404(known as PHF-1),an epitope commonly related to pathology,accumulates inside mitochondria during normal aging.This accumulation occurs preferentially in synaptic mitochondria,which suggests that it may contribute to the synaptic failure and cognitive impairment seen in aged individuals.Here,we review the main tau modifications promoting mitochondrial dysfunction,and the possible mechanism involved.Also,we discuss the evidence that supports the possibility that phosphorylated tau accumulation in synaptic mitochondria promotes synaptic and cognitive impairment in aging.Finally,we show evidence and argue about the presence of phosphorylated tau PHF-1 inside mitochondria in Alzheimer’s disease,which could be considered as an early event in the neurodegenerative process.Thus,phosphorylated tau PHF-1 inside the mitochondria could be considered such a potential therapeutic target to prevent or attenuate age-related cognitive impairment.
基金This study was supported by the National Natural Science Foundation of China(81272075 and 81801572)the Foundation of Key Discipline Construction of Zhejiang Province for Traditional Chinese Medicine(2017-XK-A36).
文摘BACKGROUND:Traumatic aortic dissection(TAD)has a low incidence but extremely high mortality.It always presents atypical clinical manifestations that are easily missed or misdiagnosed.This study mainly aims to describe the imaging characteristics and management of TAD patients.METHODS:A retrospective analysis of 27 blunt TAD patients was performed between 2013 and 2020.Demographic features,imaging characteristics,and management were analyzed.RESULTS:Twenty-seven patients with type B aortic dissection(age 56.04±16.07 years,20 men)were included.Aortic intimal tears were mostly initiated from the aortic isthmus.The sizes of the proximal intimal tears in the greater curvature were larger than those in the lesser curvature(1.78±0.56 cm vs.1.24±0.52 cm,P=0.031).Compared with those in the control group,the maximum diameters of the aortic arch,thoracic aorta,and abdominal aorta in the TAD patients were all significantly widened(all P<0.050).Multivariate logistic regression analysis showed that the maximum diameter of the thoracic aorta was an independent risk factor for TAD,with a predictive value with an area under the receiver operating characteristic curve(AUC)of 0.673.Finally,26 patients successfully underwent delayed thoracic endovascular aortic repair(TEVAR),and the remaining one patient was treated conservatively.No progression of aortic dissection or death occurred during the six-month follow-up period.CONCLUSIONS:In blunt trauma,the aortic isthmus is the most common site of proximal intimal tears.An accurate diagnosis of TAD requires an overall consideration of medical history and imaging characteristics.Delayed TEVAR might be an eff ective therapeutic option for TAD.
基金the National Natural Science Foundation of China(Grant No.81941018).
文摘In line with the worldwide trend in population aging,China has stepped into an aging society since 2000.The outstanding features of aging,including a large proportion of the older population,rapid growth,dramatic expansion of the oldest-old,and uneven aging distribution,have put China in a unique position.Besides,older population is expanding in parallel with the escalating burden of disease,high prevalence of disability,and low social involvement.However,China is not prepared to solve these problems in terms of the economy,awareness,geriatric care system,geriatric team,social security,or age-friendly environment.From the perspective of public health,we summarized the major challenges and proposed the following policy recommendations:(1)strengthening the top-level design and building a"government-leading,multi-sectoral-cooperating,and society-participating"pattern;(2)enhancing health services by implementing the"comprehensive health"strategy;(3)developing home and community care,coordinately enhance institutional care,promote integration of medical and care systems,and establish a multidimensional tailored care system;(4)optimizing geriatric the supporting system,included the construction of geriatric team and the long-term care insurance system;and(5)establishing a physical and socially age-friendly environment.
基金supported by a grant from Bayer HealthCare/Bayer Schering Pharma AG
文摘BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)imaging.However,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions and healthy tissue.This study was undertaken to evaluate the efficacy and safety of the liverspecific MR imaging contrast agent gadoxetate disodium(GdEOB-DTPA)in Chinese patients.METHODS:This was a single-arm,open-label,multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging.MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA(0.025 mmol/kg body weight).Images were evaluated by clinical study investigators and three independent,blinded radiologists.The primary efficacy endpoint was sensitivity in lesion detection.RESULTS:Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46%compared with pre-contrast imaging for the average of the three blinded readers(94.78%vs 85.32%for Gd-EOB-DTPA vs pre-contrast,respectively).Improvements in detection were more pronounced in lesions less than 1cm.Gd-EOB-DTPA improved diagnostic accuracy in lesion classification.CONCLUSIONS:This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions,particularly in those smaller than 1 cm.Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification,and furthermore,Gd-EOB-DTPA is safe in Chinese patients with liver lesions.
基金funded by the Science and Technology Planning Fundamental Research Project of Shenzhen(No.JCYJ20150324140036853)National Natural Science Foundation of China(No.61378091)+1 种基金Ningbo Natural Science Foundation Project(No.2016A610032)the Central University Basic Scientic Research Business Expenses Project(No.NSIY051405).
文摘Fluorescence lifetime is not only associated with the molecular structure f fuorophores,but alsostrongly depends on the environment around them,which llows fuorescence lifetime imagingmicroscopy(FLIM)to be used as a tool for precise measurement of the cell or tisue microenvironment,This review introduces the basic principle of fuorescence lifetime imagingtechnology and its application in clinical medicine,including research and diagnosis of diseases inskin,brain,eyes,mouth,bone,blood vessels and cavity organs,and drug evaluation.As anoninvasive,nontoxic and nonionizing radiation technique,FLIM demonstrates excellent per-formance with high sensitivity and specificity,which allows to determine precise position of thelesion and,thus,has good potential for application in biomedical research and clinical diagnosis.
文摘1 Aging in Asia-an avalanche starts to form With decreasing fertilityrate and increasing life expectan-cy, the world is aging- withhighest rates in Asia. The socio-economic, financial and medicalconsequences of the aging popu-
基金Major Research Project of Shanghai City(No. 045211024)
文摘The degradation of crosslinked polyethylene (XLPE) cable insulation during service, such as thermo-oxidation and water treeing may lead to a premature electrical breakdown of the XLPE insulation cables. Therefore, it is necessary to optimize the period of replacement to evenly distribute the replacement cost by ascertaining the deterioration degree. Estimation of the aging degree is at present the most important task for diagnosis of the residual lifetime of the power cable insulation. This paper presents a study on the changes in the dielectric properties of the thermally aged XLPE cables in the frequency range from 0.07~10 MHz. Based on electrical and physicochemical characterization, some new "dactylograms" for the thermally aged XLPE cable insulation have been proposed.
文摘The deposition of mineral phases on the heat transfer surfaces of brown coal power plants may have a negative effect on power plant boilers. The paragenesis of these deposits contains information about the actual temperature prevailed during the combustion of lignite, if the temperature-dependences of distinct mineral transformations or reactions are known. Here, we report results of a sintering study (to ?1100℃) with samples containing anhydrite, quartz, and gehlenite, which are typical components of Rhenish lignite ashes. Thermal decompositions and solid-state reactions were analyzed (1) in situ and (2) both in situ and after quenching using confocal hyperspectral Raman imaging. This novel application of confocal Raman spectroscopy provides temperature-and time-resolved, 2-dimensional information about sintering processes with a micrometer-scale resolution. In the course of the sintering experiments with anhydrite and quartz with a weight ratio of 2:1 both polymorphs wollastonite and pseudowollastonite were identified in situ at about 920 and 1000℃, respectively. The formation of pseudowollastonite was thus observed about 120℃ below the phase transition temperature, demonstrating that it can form metastably. In addition,α′L-Ca2SiO4 was identified at about 1100℃. In samples containing equal weight fractions of anhydrite and quartz that were quenched after firing for 9h at about 1100℃,β-Ca2SiO4 (larnite) crystallized as rims around anhydrite grains and in direct contact to wollastonite. We furthermore observed that, depending on the ratio between quartz and anhydrite, wollastonite replaced quartz grains between 920 and 1100℃., i.e., the higher the quartz content, the lower the formation temperature of wollastonite.
基金Supported by Foundation for the Prevention of Blindness
文摘AIM: To describe and evaluate a standardized protocol for measuring the choroidal thickness(Ch T) using enhanced depth imaging optical coherence tomography(EDI OCT).METHODS: Single 9 mm EDI OCT line scans across the fovea were used for this study. The protocol used in this study classified the EDI OCT images into four groups based on the appearance of the choroidal-scleral interface and suprachoroidal space. Two evaluation iterations of experiments were performed: first, the protocol was validated in a pilot study of 12 healthy eyes. Afterwards, the applicability of the protocol was tested in 82 eyes of patients with diabetes. Inter-observer and intra-observer agreements on image classifications were performed using Cohen’s kappa coefficient(κ). Intraclass correlation coefficient(ICC) and Bland-Altman’s methodology were used for the measurement of the Ch T.RESULTS: There was a moderate(κ=0.42) and perfect(κ =1) inter- and intra-observer agreements on image classifications from healthy eyes images and substantial(κ =0.66) and almost perfect(κ =0.86) agreements from diabetic eyes images. The proposed protocol showed excellent inter- and intra-observer agreements for the Ch T measurements on both, healthy eyes and diabetic eyes(ICC 】0.90 in all image categories). The Bland-Altman plot showed a relatively large Ch T measurement agreement in the scans that contained less visible choroidal outer boundary. CONCLUSION: A protocol to standardize Ch T measurements in EDI OCT images has been developed;the results obtained using this protocol show that the technique is accurate and reliable for routine clinical practice and research.
文摘<strong>Background:</strong> Young and intact skin is highly responsive. As skin ages, its responsiveness decreases. Production of structural components of the skin slows down and signs of skin aging appear. External influences like UV radiation and pollution contribute to signs of skin aging. They lead to an increased formation of so-called free radicals. Bioactive antioxidant compounds, such as polyphenols, have beneficial effects on skin health by free radical scavenging. The purpose of this study was to evaluate the topical effects of new and highly concentrated resveratrol containing emulsion (Medskin Solutions Dr. Suwelack AG, 2% trans-resveratrol) on age-related alterations to the skin. <strong>Methods:</strong> A clinical observation study was performed on 20 subjects to observe the effects of a 2% resveratrol emulsion on typical signs of skin aging. Product was applied once daily for a period of 8 weeks in combination with a standardized treatment. Tested parameters were skin elasticity, skin barrier function, skin smoothness, skin thickness and density. <strong>Results:</strong> After 8 weeks of treatment, skin pH value is significantly lowered and skin barrier function improved. The value of skin elasticity (+5.3%), and skin density (+ 10.7%) had increased, while skin roughness (-6.4%) and skin dispensability (-45.9%) had diminished. Intensity of skin redness had decreased. Furthermore, expert and participant evaluations show satisfaction, especially with regard to skin smoothness and skin moisture. Conclusion: The resveratrol emulsion shows positive outcomes by supporting reduction of skin wrinkling and increasing skin firmness, as well as reducing skin redness, and is therefore an all-round anti-aging treatment.
基金MT received studentship from Sao Paulo Research Foundation(2017/21655-6)HSB was a Brazilian National Council for Scientific and Technological Development researcher(425838/2016-1,307252/2017-5)This work was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil(CAPES)–Finance Code 001 and FAPESP(2016/07115-6).
文摘Aging is a dynamic and progressive process that begins at conception and continues until death.This process leads to a decrease in homeostasis and morphological,biochemical and psychological changes,increasing the individual’s vulnerability to various diseases.The growth in the number of aging populations has increased the prevalence of chronic degenerative diseases,impairment of the central nervous system and dementias,such as Alzheimer’s disease,whose main risk factor is age,leading to an increase of the number of individuals who need daily support for life activities.Some theories about aging suggest it is caused by an increase of cellular senescence and reactive oxygen species,which leads to inflammation,oxidation,cell membrane damage and consequently neuronal death.Also,mitochondrial mutations,which are generated throughout the aging process,can lead to changes in energy production,deficiencies in electron transport and apoptosis induction that can result in decreased function.Additionally,increasing cellular senescence and the release of proinflammatory cytokines can cause irreversible damage to neuronal cells.Recent reports point to the importance of changing lifestyle by increasing physical exercise,improving nutrition and environmental enrichment to activate neuroprotective defense mechanisms.Therefore,this review aims to address the latest information about the different mechanisms related to neuroplasticity and neuronal death and to provide strategies that can improve neuroprotection and decrease the neurodegeneration caused by aging and environmental stressors.