1.Pathophysiological implications of cellular senescence and prospects for novel anti-aging drugs.
Acta Physiologica Sinica 2023;75(6):847-863
Chronological aging is the leading risk factor for human diseases, while aging at the cellular level, namely cellular senescence, is the fundamental driving force of organismal aging. The impact of cellular senescence on various life processes, including normal physiology, organismal aging and the progress of various age-related pathologies, has been largely ignored for a long time. However, with recent advancement in relevant fields, cellular senescence has become the core of aging biology and geriatric medicine. Although senescent cells play important roles in physiological processes including tissue repair, wound healing, and embryonic development, they can also contribute to tissue dysfunction, organ degeneration and various pathological conditions during adulthood. Senescent cells exert paracrine effects on neighboring cells in tissue microenvironments by developing a senescence-associated secretory phenotype, thus maintaining long-term and active intercellular communications that ultimately results in multiple pathophysiological effects. This is regarded as one of the most important discoveries in life science of this century. Notably, selective elimination of senescent cells through inducing their apoptosis or specifically inhibiting the senescence-associated secretory phenotype has shown remarkable potential in preclinical and clinical interventions of aging and age-related diseases. This reinforces the belief that senescent cells are the key drug target to alleviate various aging syndromes. However, senescent cells exhibit heterogeneity in terms of form, function and tissue distribution, and even differ among species, which presents a challenge for the translation of significant research achievements to clinical practice in future. This article reviews and discusses the characteristics of senescent cells, current targeting strategies and future trends, providing useful and valuable references for the rapidly blooming aging biology and geriatric medicine.
Humans
;
Adult
;
Aged
;
Cellular Senescence/genetics*
;
Aging
;
Apoptosis
;
Cell Communication
;
Wound Healing/physiology*
2.Neurovascular coupling responses and cognitive function: The impact of aging and the interventional effect of exercise.
Yi-Min HE ; Chun-Li WU ; Yu-Mo DONG ; Hua-Duo WU ; Qian WANG ; Ning JIANG
Acta Physiologica Sinica 2023;75(6):903-917
Aging is a natural process accompanied with a progressive deterioration of cognitive functions. With an aging population, more and more elderly people are suffering from cognitive impairment. Previous studies have paid more attention to the impact of inflammation and oxidative stress on cognitive function during aging. Recently, it has been discovered that neurovascular coupling (NVC), a mechanism regulating cerebral blood flow, may play a significant role in aging-related cognitive impairment. NVC responses regulate the supply of energy substances and oxygen during brain activity, which in turn enhances cognitive function. However, as people grow older, NVC responses gradually weaken, which may be one of the mechanisms underlying aging-induced cognitive impairment. Given the important role of NVC responses in the brain, it is necessary to search for intervention methods that can improve NVC responses and promote cognitive function. Exercise is an effective means to delay aging and improve cognitive function. It also has a certain promoting effect on NVC responses. This article reviews the regulatory mechanisms of NVC responses, the relationship between NVC responses and cognitive function, and explores the effects of aging and exercise intervention on NVC responses, hoping to provide new research ideas for exercise intervention to improve NVC responses and promote cognitive function in the elderly.
Humans
;
Aged
;
Neurovascular Coupling/physiology*
;
Aging
;
Cerebrovascular Circulation/physiology*
;
Cognition
;
Brain
3.Alterations of Audiovisual Integration in Alzheimer's Disease.
Yufei LIU ; Zhibin WANG ; Tao WEI ; Shaojiong ZHOU ; Yunsi YIN ; Yingxin MI ; Xiaoduo LIU ; Yi TANG
Neuroscience Bulletin 2023;39(12):1859-1872
Audiovisual integration is a vital information process involved in cognition and is closely correlated with aging and Alzheimer's disease (AD). In this review, we evaluated the altered audiovisual integrative behavioral symptoms in AD. We further analyzed the relationships between AD pathologies and audiovisual integration alterations bidirectionally and suggested the possible mechanisms of audiovisual integration alterations underlying AD, including the imbalance between energy demand and supply, activity-dependent degeneration, disrupted brain networks, and cognitive resource overloading. Then, based on the clinical characteristics including electrophysiological and imaging data related to audiovisual integration, we emphasized the value of audiovisual integration alterations as potential biomarkers for the early diagnosis and progression of AD. We also highlighted that treatments targeted audiovisual integration contributed to widespread pathological improvements in AD animal models and cognitive improvements in AD patients. Moreover, investigation into audiovisual integration alterations in AD also provided new insights and comprehension about sensory information processes.
Animals
;
Humans
;
Alzheimer Disease/pathology*
;
Brain/pathology*
;
Aging/physiology*
;
Cognition
4.The concept and development direction of elderly oriented food.
Jian ZHANG ; Wen Hua ZHAO ; Jun Shi CHEN
Chinese Journal of Preventive Medicine 2023;57(11):1915-1917
Active response to the challenges posed by aging has been established as a national strategy, accompanied by continuous refinement of policies concerning aging work. Decreased digestive system function is commonly present in the natural aging process of older people, which directly affects their food intake, digestion, and absorption, leading to decreased appetite and various forms of malnutrition. It is also a risk factor for age-related diseases such as sarcopenia, osteoporosis, cognitive impairment, and frailty. Nutrition is the foundation for achieving healthy aging. In order to meet the nutritional needs of the elderly population, the Nutrition and Healthy Aging Working Group at the Shanghai Junshi Institute of Life Sciences introduced the concept of "elderly-oriented food" in 2022. In the future, there is an urgent need for comprehensive collaborative efforts to conduct a series of investigations focused on the dietary habits and nutritional requirements of older individuals, in order to evaluate the level of awareness, genuine demands, dietary preferences, and capabilities of selection regarding to the elderly-oriented food. Simultaneously, it is recommended to introduce "Guidelines for the production and application of elderly-oriented food" at the national level to promote the sustainable and orderly development in food industry.
Humans
;
Aged
;
China
;
Nutritional Status
;
Aging/physiology*
;
Malnutrition/prevention & control*
;
Diet
5.The concept and development direction of elderly oriented food.
Jian ZHANG ; Wen Hua ZHAO ; Jun Shi CHEN
Chinese Journal of Preventive Medicine 2023;57(11):1915-1917
Active response to the challenges posed by aging has been established as a national strategy, accompanied by continuous refinement of policies concerning aging work. Decreased digestive system function is commonly present in the natural aging process of older people, which directly affects their food intake, digestion, and absorption, leading to decreased appetite and various forms of malnutrition. It is also a risk factor for age-related diseases such as sarcopenia, osteoporosis, cognitive impairment, and frailty. Nutrition is the foundation for achieving healthy aging. In order to meet the nutritional needs of the elderly population, the Nutrition and Healthy Aging Working Group at the Shanghai Junshi Institute of Life Sciences introduced the concept of "elderly-oriented food" in 2022. In the future, there is an urgent need for comprehensive collaborative efforts to conduct a series of investigations focused on the dietary habits and nutritional requirements of older individuals, in order to evaluate the level of awareness, genuine demands, dietary preferences, and capabilities of selection regarding to the elderly-oriented food. Simultaneously, it is recommended to introduce "Guidelines for the production and application of elderly-oriented food" at the national level to promote the sustainable and orderly development in food industry.
Humans
;
Aged
;
China
;
Nutritional Status
;
Aging/physiology*
;
Malnutrition/prevention & control*
;
Diet
6.Loss of KDM4B impairs osteogenic differentiation of OMSCs and promotes oral bone aging.
Peng DENG ; Insoon CHANG ; Jiongke WANG ; Amr A BADRELDIN ; Xiyao LI ; Bo YU ; Cun-Yu WANG
International Journal of Oral Science 2022;14(1):24-24
Aging of craniofacial skeleton significantly impairs the repair and regeneration of trauma-induced bony defects, and complicates dental treatment outcomes. Age-related alveolar bone loss could be attributed to decreased progenitor pool through senescence, imbalance in bone metabolism and bone-fat ratio. Mesenchymal stem cells isolated from oral bones (OMSCs) have distinct lineage propensities and characteristics compared to MSCs from long bones, and are more suited for craniofacial regeneration. However, the effect of epigenetic modifications regulating OMSC differentiation and senescence in aging has not yet been investigated. In this study, we found that the histone demethylase KDM4B plays an essential role in regulating the osteogenesis of OMSCs and oral bone aging. Loss of KDM4B in OMSCs leads to inhibition of osteogenesis. Moreover, KDM4B loss promoted adipogenesis and OMSC senescence which further impairs bone-fat balance in the mandible. Together, our data suggest that KDM4B may underpin the molecular mechanisms of OMSC fate determination and alveolar bone homeostasis in skeletal aging, and present as a promising therapeutic target for addressing craniofacial skeletal defects associated with age-related deteriorations.
Aging
;
Cell Differentiation
;
Facial Bones/physiology*
;
Humans
;
Jumonji Domain-Containing Histone Demethylases/genetics*
;
Mesenchymal Stem Cells/cytology*
;
Osteogenesis
;
Osteoporosis
7.The measurements of the similarity of dynamic brain functional network.
Yongquan HE ; Li ZHANG ; Shan FANG ; Yaqin ZENG ; Wei YANG ; Weidong CHEN ; Yuling SHAO ; Ruidong CHENG ; Xiangming YE ; Dongrong XU
Journal of Biomedical Engineering 2022;39(2):237-247
Brain functional network changes over time along with the process of brain development, disease, and aging. However, most of the available measurements for evaluation of the difference (or similarity) between the individual brain functional networks are for charactering static networks, which do not work with the dynamic characteristics of the brain networks that typically involve a long-span and large-scale evolution over the time. The current study proposes an index for measuring the similarity of dynamic brain networks, named as dynamic network similarity (DNS). It measures the similarity by combining the "evolutional" and "structural" properties of the dynamic network. Four sets of simulated dynamic networks with different evolutional and structural properties (varying amplitude of changes, trend of changes, distribution of connectivity strength, range of connectivity strength) were generated to validate the performance of DNS. In addition, real world imaging datasets, acquired from 13 stroke patients who were treated by transcranial direct current stimulation (tDCS), were used to further validate the proposed method and compared with the traditional similarity measurements that were developed for static network similarity. The results showed that DNS was significantly correlated with the varying amplitude of changes, trend of changes, distribution of connectivity strength and range of connectivity strength of the dynamic networks. DNS was able to appropriately measure the significant similarity of the dynamics of network changes over the time for the patients before and after the tDCS treatments. However, the traditional methods failed, which showed significantly differences between the data before and after the tDCS treatments. The experiment results demonstrate that DNS may robustly measure the similarity of evolutional and structural properties of dynamic networks. The new method appears to be superior to the traditional methods in that the new one is capable of assessing the temporal similarity of dynamic functional imaging data.
Aging/physiology*
;
Brain/physiology*
;
Brain Mapping
;
Humans
;
Magnetic Resonance Imaging/methods*
;
Nerve Net/physiology*
;
Transcranial Direct Current Stimulation/methods*
8.Quantitative assessment of the aging corpus cavernosum by shear wave elastography.
Hao CHENG ; Guo-Xiong LIU ; Fei WANG ; Ke WANG ; Li-Tao RUAN ; Lin YANG
Asian Journal of Andrology 2022;24(6):628-632
We wanted to determine whether shear wave elastography (SWE) could be used to evaluate the aging degree of the corpus cavernosum (CC) and to identify the histological basis of changes in SWE measurements during the aging process. We performed a cross-sectional study enrolling healthy participants of different ages. We measured the Young's modulus (YM) of the penile CCs by SWE and assessed erectile function using the International Index of Erectile Function-5 (IIEF-5). Histological investigation was performed in surgically resected penile specimens from a separate group of patients to examine the smooth muscle and collagen content of the CCs. Furthermore, we measured the YM, erectile function, smooth muscle, and collagen content of the CCs in different age groups of rats. Finally, we enrolled 210 male volunteers in this study. The YM of the CC (CCYM) was positively correlated with age (r = 0.949, P < 0.01) and negatively correlated with erectile function (r = -0.843, P < 0.01). Histological examinations showed that CCs had increased collagen content but decreased smooth muscle content with increased age. The same positive correlation between CCYM and age was also observed in the animal study. In addition, the animal study showed that older rats, with increased CCYM and decreased erectile function, had lower smooth muscle content and higher collagen content. SWE can noninvasively and quantitatively evaluate the aging degree of the CC. Increased collagen content and decreased smooth muscle content might be the histological basis for the effect of aging on the CC and the increase in its YM.
Humans
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Male
;
Rats
;
Animals
;
Erectile Dysfunction
;
Elasticity Imaging Techniques
;
Cross-Sectional Studies
;
Penis/pathology*
;
Penile Erection/physiology*
;
Aging
;
Collagen
9.Differences of body composition and physical strength among Japanese and Thai older adults living in Chiang Mai, Thailand: an inter-ethnic cross-sectional study.
Takeshi YODA ; Bumnet SAENGRUT ; Kensaku MIYAMOTO ; Rujee RATTANASATHIEN ; Tatsuya SAITO ; Yasuko ISHIMOTO ; Kanlaya CHUNJAI ; Rujirat PUDWAN ; Kawin SIRIMUENGMOON ; Hironobu KATSUYAMA
Environmental Health and Preventive Medicine 2021;26(1):97-97
BACKGROUND:
The number of adults aged over 65 years is rapidly increasing in several Southeast Asian countries. Muscle mass decreases with age, leading to sarcopenia. The primary objective of this study was to determine whether differences exist in the body composition and physical strength, according to ethnicity, among community-dwelling Japanese and Thai older adults living in Chiang Mai Province, Thailand.
METHODS:
A survey was conducted in February and March 2019. Japanese and Thai adults aged ≥ 60 years living in Chiang Mai Province were recruited through community clubs. Participants completed a self-administered questionnaire that enabled collection of data on age, sex, educational background, marital status, annual income, current medical conditions, smoking and alcohol consumption, and exercise habits. Measurements were collected on height, weight, body composition, blood pressure, hand grip, and walking speed for 6 m. Body composition was measured using a standing-posture 8-electrode multifrequency bioimpedance analysis analyzer. Hand grip of each hand was measured with the patient in the standing position using a digital grip dynamometer. Multivariable logistic regression was used to determine factors associated with skeletal muscle mass index (SMI).
RESULTS:
Of the total 119 participants, 47 were Japanese (26 men, 21 women) and 72 were Thai (16 men, 56 women). The prevalence of a low SMI was 3/26 (12%), 1/21 (5%), 6/16 (38%), and 5/56 (9%) among Japanese men, Japanese women, Thai men, and Thai women, respectively. The prevalence of low muscle strength was 2/26 (8%), 2/21 (10%), 3/16 (19%), and 13/56 (23%) among Japanese men, Japanese women, Thai men, and Thai women, respectively. There were significant differences between ethnic groups in body mass index for both sexes, percentage body fat in women, SMI in men, and average grip strength in men. Ethnic group, sex, age, and body mass index were independent predictors of SMI.
CONCLUSIONS
Ethnicity had a clinically important effect on body composition and physical strength among older Japanese and Thai adults living in a similar environment.
Aged
;
Aging/physiology*
;
Asians/ethnology*
;
Body Composition
;
Body Mass Index
;
Cross-Sectional Studies
;
Electric Impedance
;
Ethnicity
;
Female
;
Hand Strength
;
Humans
;
Independent Living
;
Male
;
Middle Aged
;
Muscle Strength
;
Thailand/ethnology*
;
Walking Speed
10.A review on brain age prediction in brain ageing.
Lan LIN ; Jingxuan WANG ; Zhenrong FU ; Xuetao WU ; Shuicai WU
Journal of Biomedical Engineering 2019;36(3):493-498
The human brain deteriorates as we age, and the rate and the trajectories of these changes significantly vary among brain regions and among individuals. Because neuroimaging data are potentially important indicators of individual's brain health, they are commonly used in brain age prediction. In this review, we summarize brain age prediction model from neuroimaging-based studies in the last ten years. The studies are categorized based on their image modalities and feature types. The results indicate that the prediction frameworks based on neuroimaging holds promise toward individualized brain age prediction. Finally, we addressed the challenges in brain age prediction and suggested some future research directions.
Aging
;
Brain
;
diagnostic imaging
;
physiology
;
Humans
;
Neuroimaging

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