Aging and Disease最新文献

Population aging has become a widespread health problem that leads to huge socioeconomic burden. Skeletal muscle as an important component of motor system, gradually degenerates with age. Age-related muscle disorders, such as sarcopenia is associated with higher risks of falls, fracture, disability, and mortality in old people. As there is still no Food and Drug Administration (FDA) approved drug to treat sarcopenia, conducting research of in-depth mechanisms is warranted to develop novel treatments. The cutting-edge techniques single-cell and single-nuclei RNA sequencing can help to address this issue by discovering age-related changes of muscle at the single-cell level. This review aims to systematically explore current evidence of age-related muscle changes during normal aging, regeneration, and after treatments at the single-cell level. 29 studies were eligible and included in the current review according to the PRISMA guideline. The muscle cell composition was altered with age, such as diminished muscle stem cells (MuSCs), vascular cells, Schwann cells, and increased myocytes as well as some types of immune cells. Inflammation levels, collagen and extracellular matrix (ECM) signaling, protein catabolism, TGFβ signaling, apoptosis, and autophagy of MuSCs, myocytes, fibro-adipogenic progenitor cells, vascular cells, or immune cells were regulated with age. Delayed muscle regeneration of aged muscle was relied on disorders of cell-specific immune response, myogenesis, angiogenesis, and ECM remodeling. Three treatments involved in this review could reverse age-related dysfunction of muscle cells to some extent. Further research targeting age-related changes of muscle at the single-cell level is an important tool in assisting development of more effective treatments for sarcopenia.

Previous research has identified externalized phosphatidylserine (PS) as an "eat me" signal in apoptosis regulation. Targeting PS thus represents a promising therapeutic approach. Annexin A5, known for its high affinity for PS, has traditionally been used as a FITC-labeled probe for detecting apoptosis. Recent studies have demonstrated that Annexin A5 can cross the blood-brain barrier and selectively bind to PS-exposed injured tissues, exerting multiple protective effects, such as anticoagulant, anti-inflammatory, and anti-apoptotic actions. Furthermore, emerging evidence suggests that Annexin A5 holds potential for molecular imaging of the ischemic penumbra and for the development of lesion-targeted drug delivery systems. In summary, Annexin A5 has garnered increasing attention for its neuroprotective properties and therapeutic potential. Ischemic stroke is one of the leading causes of disability and mortality worldwide. Ischemic stroke management still requires effective neuroprotective agents and innovative imaging strategies to improve clinical outcomes. This article provides a comprehensive analysis of protective mechanisms and translational applicability of Annexin A5 in ischemic stroke therapy, offering novel insights for the development of next-generation multi-target cerebrovascular interventions.

Transcatheter aortic valve replacement (TAVR) is widely recommended and applied among patients with severe aortic stenosis. However, considering the complicated situation of patients after TAVR, Cardiac rehabilitation (CR), as a well-established program to improve the outcome and quality of life, has not been underexploited among them yet. The purpose of this review is to discuss the current challenges of carrying out the post-TAVR CR program, compare different evaluation programs, and develop a relatively reasonable and standardised post-TAVR CR program based on "The Five Prescriptions" of Guidelines for cardiovascular rehabilitation and secondary prevention in China. Constructed from physical intervention, psychological intervention, nutritional intervention, and life management, the post-TAVR CR program targets a combination of universal and tailored approaches for patients.

Aging is a gradual loss of tissue homeostasis that leads to impaired physiological organ functions and constitutes a major risk factor for cancer initiation and progression. Despite advances in anti-tumor therapies, cancer remains the second leading cause of death worldwide. The rising incidence of cancer is intimately associated with increased lifespan and the growing proportion of older adults, with 64% of cancers diagnosed in people aged 60 and above. Mechanisms underlying aging include accumulation of somatic mutations, deficient DNA damage repair machinery, telomere shortening, enhanced genomic instability, epigenetic alterations, loss of heterochromatin, chronic low-grade inflammation, mitochondrial dysfunction, cellular senescence and its associated secretory phenotype, stem cell exhaustion, aberrant intercellular communications, remodeling of extracellular matrix and microenvironment, impaired nutrient sensing and alterations in the proteome. Additionally, dysregulation of the circadian clock, the endocannabinoid system and the microbiota may also play important roles. Given that many of these processes are also crucial for cancer development, it is widely admitted that aging and cancer are tightly interconnected. Consequently, many therapies aimed at delaying or mitigating aging, such as physical exercise, specific dietary regimens, chronotherapy, epigenetic drugs and senotherapeutics, might also prevent or retard cancer development and progression and reduce the side effects of cancer therapies. However, special caution must be taken in older cancer patients due to their comorbidities and possible frailty, selecting specific patients' treatments and balancing the extended survival with the preservation of independence and quality of life.

Physiological functions of astrocytes, the most abundant cell type in the brain, are important in maintaining many central nervous system (CNS) functions. In this review, we summarized astrocytes' normal physiological roles. However, under the pathological conditions of Alzheimer's Disease (AD), astrocytes pause their homeostatic roles to address and contain abnormal changes in AD brains in response to Aβ deposits, neuroinflammation, and neurodegeneration. The chronic perturbation in AD brains causes various populations of astrocytes to permanently forgo their physiological roles throughout different regions of the brain to contain disease progression. This transition leads to reactive astrogliosis, in which astrocytes transform into reactive phenotypes that eventually contribute to pathological severity. The transformations in astrocytes can negatively impact their morphology and mobility, inflammatory response, energy metabolism, and their ability to properly degrade Aβ deposits. We reviewed recent literature exploring the underlying mechanisms on how AD induces astrocyte morphological, transcriptional, and functional changes. Together, these findings reveal that loss of astrocyte homeostatic function and transformations into neurotoxic states contribute to AD pathology throughout each stage of disease progression. Thus, aims to restore astrocyte homeostatic functions by developing astrocyte-specific therapeutic targets to attenuate AD pathology and clinical manifestations are warranted.

Disruptions in glial-neuron communication are linked to brain diseases; however, the exact mechanisms are not yet fully understood. This review highlights the critical role of glia-neuron interactions in sustaining normal brain functions. Under physiological conditions, astrocytes, microglia and oligodendrocytes, collaboratively regulate the homeostasis of brain structures and functions through diverse communication mechanisms. Conversely, under pathological conditions, disorders in glial-neuron communication can precipitate in neurodegenerative diseases, such as Alzheimer's Disease (AD). In AD, astrocytes use APOE to increase amyloid-beta (Aβ) deposition in the brain extracellular space (ECS) and neuron death, while microglia overactivation causes Tau overexpression and oligodendrocyte demyelination, leading to communication issues. Toxic proteins, Aβ and Tau, block brain ECS and hinder the drainage of interstitial fluid (ISF) cause the vicious cycle. The obstruction of ISF drainage certainly impedes neurotransmitter transmission, nutrient delivery, and waste removal, ultimately leading to neuronal death and cognitive decline in AD, which is also a direct factor contributing to the failure of drug delivery. Age-associated formaldehyde (FA) may act as a detrimental factor that exacerbates Aβ aggregation and promotes tau hyperphosphorylation, further aggravating ECS and ISF dysfunction. Interestingly, the interrupting the pathological cycle of FA-promoted Aβ aggregation and Aβ-induced FA generation by phototherapy and nanomedicine has been found to restore the ECS architecture and ISF drainage, which effectively improves AD symptoms. Hence, the re-establishing ECS structure and communication between neurons and glial cells may offer a promising therapeutic strategy for treating AD.

Accumulating evidence implicates hallmarks of brain aging, namely oxidative stress, reactive gliosis, and cellular senescence, as key contributors to hippocampal dysfunction and associated age-related cognitive deficits. Astrocytes robustly express antioxidants such as superoxide dismutases to detoxify reactive oxygen species (ROS) generated as a result of the high metabolic activity in the brain. However, aging is associated with transcriptional downregulation of antioxidant genes concomitant with polarization towards reactive, proinflammatory phenotypes in astrocytes. Given prior findings that astrocyte-specific ablation of SOD2 induces phenotypes of cognitive aging, we hypothesized that enhancing astrocyte antioxidant capacity via SOD2 overexpression (aSOD2OE) would ameliorate molecular hallmarks of aging and preserve cognitive function. To test this, we overexpressed SOD2 in astrocytes of aged (22 mo) male C57Bl/6N mice using an AAV(PHP.eB)-GFAP-hSOD2 viral vector and assessed hippocampal-dependent spatial working memory using a high-resolution, automated home-cage behavioral testing platform. We found that aSOD2OE significantly improved spatial working memory performance compared to aged GFP controls. Using molecular and histological approaches, aSOD2OE was associated with reductions in markers of cellular senescence and reactive astrogliosis within the hippocampus. These findings suggest that enhancement of astrocyte mitochondrial antioxidant activity is sufficient to alleviate maladaptive cellular programs associated with cognitive decline. Together, these data identify astrocyte redox biology as a potential therapeutic target in preserving hippocampal function in aging.

Heart failure (HF) is a common comorbidity for older patients of chronic obstructive pulmonary disease (COPD). This study aimed to investigate the global burden of COPD-HF comorbidity among older adults from 1990 to 2021 and make a prediction till 2050. Data on prevalence and years lived with disability (YLDs) for COPD-HF comorbidity among older adults aged 60 or above were obtained from the Global Burden of Diseases Study 2021. Absolute number and age-standardized rate (ASR) per 100,000 individuals were used to compare the disease burden by sex, age, severity and region. Temporal trends in ASR from 1990 to 2021 were analyzed using Joinpoint models, while Bayesian age-period-cohort models were introduced to project ASR till 2050. From 1990 to 2021, global prevalent cases and YLDs of COPD-HF comorbidity among older adults increased, and ASRs also exhibited a sustained increase. The disease burden will continue to rise till 2050. Moreover, the comorbidity burden was higher in males than females, and increased with age. Additionally, severe and treated cases were the predominant subtypes of this comorbidity. Low and middle socio-demographic index (SDI) regions tended to bear higher disease burden. The global burden of COPD-HF comorbidity was substantially heavy with a consistent rising trend from 1990 to 2021 in older adults. The disease burden will rise till 2050. Disparities of the disease burden existed in sex, SDI, and geographic region worldwide. This study has implications for re-allocating resources to early identification and effective treatment of COPD, HF, and COPD-HF comorbidity.

Stroke has a profound effect on the retina's function, resulting in ischemia, nerve fiber thinning, microvascular issues, and breakdown of the blood-retina barrier. This leads to visual problems, including field defects, lower acuity, and damage to photoreceptors. In this comprehensive review, we delve into the historical milestones, diagnostic breakthroughs, and therapeutic approaches, with a particular focus on the retina as both a marker of and a target for addressing stroke-related dysfunction. Firstly, the retina is a non-invasive method for assessing cerebrovascular health, as it shares the same embryological origins and structural similarities with the brain. In addition, new imaging technologies, such as optical coherence tomography (OCT) and OCT angiography (OCTA), have revolutionized the way we detect alterations in the retina and their relationship to brain diseases. These developments have shown strong connections between retinal changes and cerebral pathologies, opening up new frontiers in our understanding and management of stroke-related retinal issues. Furthermore, new treatments, such as anti-inflammatory and antioxidant therapy, along with collaboration between doctors in other fields, including ophthalmology, neurology, and rehabilitation, demonstrate the importance of providing each patient with the proper care. At last, translational research, which connects biological discoveries with therapeutic uses, shows promise for improving early diagnosis, rehabilitation procedures, and outcomes for people who have had a stroke. Together, these advances position the retina as a powerful platform for understanding stroke pathology and developing innovative diagnostic and therapeutic strategies.

Specific wavelengths and intensities of light offer potential for modulating mitochondrial function to influence aging which is important for the development of non-invasive and modifiable exogenous anti-aging tools. However, the effects of exposure to different wavelengths of light during the early stages of life on health in adulthood, and the underlying mechanisms, remain poorly understood. In this study, we utilized Caenorhabditis elegans to investigate the effects of early-life (L1 to young adult stage) exposure to different light wavelengths (white, red, blue, green) on healthspan. We found that red light exposure (630 nm, 200 lx) during early life extended lifespan by 10.34% without affecting growth, movement, or reproduction, and improved late-life health indicators. Importantly, it significantly enhanced healthspan in later life, suggesting its potential as a non-invasive anti-aging strategy. Mechanistically, red light transiently suppressed mitochondrial bioenergetic activity, biogenesis, and membrane potential, and altered mitochondrial dynamics. Upon light withdrawal, mitochondrial function progressively recovered, demonstrating enhanced structure and function by day 6. Furthermore, red light stimulated ROS production, activated AMPKα phosphorylation, and triggered downstream mitochondrial quality control (MQC) programs, including the unfolded protein response (UPR^MT) and mitophagy. Notably, these protective effects were conserved in human dermal fibroblasts, suggesting the translational applicability of this pathway. Collectively, our study identifies a specific "photophysiological window" during early life through which red light promotes longevity via ROS-mediated activation of AMPK and enhancement of MQC, proposing a non-invasive, safe, evolutionarily conserved, and drug-free strategy to mitigate age-related mitochondrial decline. Therefore, red light can serve as a non-invasive anti-aging strategy to enhance healthspan and potentially alleviate age-related mitochondrial dysfunction.