Aging and Disease最新文献

Vascular aging is the pathological basis for the aging of various organ systems in the human body and is a common pathogenesis leading to the development of atherosclerosis, Alzheimer's disease, and other conditions among older adults. Aging is characterized by accelerated pulse wave velocity, thickening of the carotid artery intima-media, and decreased vascular dilation function. Signaling pathways such as mTOR, AMPK, NF-κB, Klotho, SIRT, and other key proteins are likely involved in these processes. The detection of biomarkers related to vascular aging, including senescence-associated β-galactosidase, endothelial progenitor cells, circulating endothelial microparticles, and exosomal miRNAs, aids in assessing vascular status and prognosis. Repairing endothelial injury, reducing oxidative stress-inflammatory responses, and restoring mitochondrial and telomere functions are reliable measures to counter vascular aging. In summary, research on vascular aging is the driving force that will provide rational strategies to intervene in geriatric vascular diseases and achieve the long-term goal of healthy aging.

Senescence is a cellular state characterized by an irreversible halt in the cell cycle, accompanied by alterations in cell morphology, function, and secretion. Senescent cells release a plethora of inflammatory and growth factors, extracellular matrix proteins, and other bioactive substances, collectively known as the senescence-associated secretory phenotype (SASP). These excreted substances serve as crucial mediators of senescent tissues, while the secretion of SASP by senescent neurons and glial cells in the central nervous system modulates the activity of immune cells. Senescent immune cells also influence the physiological activities of various cells in the central nervous system. Further, the interaction between cellular senescence and immune regulation collectively affects the physiological and pathological processes of the central nervous system. Herein, we explore the role of senescence in the physiological and pathological processes underlying embryonic development, aging, degeneration, and injury of the central nervous system, through the immune response. Further, we elucidate the role of senescence in the physiological and pathological processes of the central nervous system, proposing a new theoretical foundation for treating central nervous system diseases.

Age-related hearing loss (ARHL) is a disease that impacts human quality of life and contributes to the progression of other neuronal problems. Various stressors induce an increase in free radicals, destroy mitochondria to further contribute to cellular malfunction, and compromise cell viability, ultimately leading to functional decline. Cisd2, a master gene for Marfan syndrome, plays an essential role in maintaining mitochondrial integrity and functions. As shown by our data, specific deletion of Cisd2 in the cochlea exacerbated the hearing impairment of ARHL in C57BL/6 mice. Increased defects in mitochondrial function, potassium homeostasis and synapse activity were observed in the Cisd2-deleted mouse models. These mechanistic phenotypes combined with oxidative stress contribute to cell death in the whole cochlea. Human patients with obviously deteriorated ARHL had low Cisd2 expression; therefore, Cisd2 may be a potential target for designing therapeutic methods to attenuate the disease progression of ARHL.

Abnormally elevated oxidative stress underlies many diseases and contributes to aging. The myeloid enzyme myeloperoxidase (MPO) generates oxidative stress and contributes to damage after stroke. How aging changes MPO in stroke has not been studied. We aimed to determine the effects aging has on MPO and how these changes contribute to age-related differences in outcomes after ischemic stroke. To investigate tissue MPO activity we developed MPO Activatable Fluorescent Agent (MAFA). We found that aged mice exhibited worse neurological outcomes and higher mortality within the first few days after stroke. Accordingly, neuronal loss was higher in aged mice on day 3. MAFA imaging revealed that aged brains have markedly higher MPO activity that increased after stroke on day 3 compared to young adult brains. Correspondingly, we found more Iba1⁺ cells in aged brains compared to young adult brains before and after stroke. Interestingly, we found decreased percentage of MPO⁺ cells and lower MPO protein levels in aged on day 3, suggesting that most Iba1⁺ cells in aged mice have degranulated and secreted MPO in response to stroke. By day 10 MPO activity and Iba1⁺ cells decreased in both age groups, although MPO activity remained higher in aged mice. MPO inhibition in aged mice decreased MAFA signal and Iba1⁺ cells and improved neurobehavioral outcomes to near young adult stroke mice levels and improved mortality rate. While aging is an unmodifiable risk, by uncovering the connection between aging and MPO-related changes after stroke, new therapies can be developed to mitigate these adverse changes brought upon by aging.

Biological age is a personalized measure of the health status of an organism, organ, or system, as opposed to simply accounting for chronological age. To date, there have been known attempts to create estimators of biological age based on various biomedical data. In this work, we focused on developing an approach for assessing heart biological age using echocardiographic data. The current study included echocardiographic data from more than 5,000 different cases. As a result, we created EchoAGE - neural network model to determine heart biological age, that was tested on echocardiographic data from patients with age-related diseases, patients with multimorbidity, children with progeria syndrome, and diachronic data series. The model estimates biological age with a Mean Absolute Error of approximately 3.5 years, an R-squared value of around 0.88, and a Spearman's rank correlation coefficient greater than 0.9 in men and women. EchoAGE uses indicators such as E/A ratio of maximum flow rates in the first and second phases, thicknesses of the interventricular septum and the posterior left ventricular wall, cardiac output, and relative wall thickness. In addition, we have applied an AI explanation algorithm to improve understanding of how the model performs an assessment.

Although the pursuit of eternal youth remains elusive, progress in the fields of medicine and science has greatly extended the human lifespan. Nevertheless, the rising incidence of diseases and their economic impact present notable obstacles. Mitochondria-associated membranes (MAMs), essential sites for close interaction between mitochondria and the endoplasmic reticulum (ER), are increasingly recognized for their involvement in both normal cellular processes and the development of diseases. Studies suggest that MAMs undergo dynamic alterations, particularly pertinent in the investigation of age-related illnesses. This review highlights the significance of MAMs in age-related conditions, elucidating the morphological and functional alterations in mitochondria and ER during aging. By emphasizing the complex interaction between these organelles, it demonstrates the cell's adaptive responses to combat age-related deterioration. Suggesting MAMs as potential targets for therapeutic interventions holds the potential for attenuating the progression of age-related diseases.

Alzheimer's Disease (AD) is the most prevalent, costly, and fatal neurodegenerative disorder of this century. Two hallmark features of AD are the anomalous cleavage of amyloid precursor protein (APP), which leads to the accumulation of amyloid-beta (Aβ), and the hyperphosphorylation of tau protein. Despite extensive research efforts, the pathology and pathogenesis of AD remain elusive. Recent investigations have highlighted the close association between antisense long non-coding RNAs (AS-lncRNAs) and various biological and functional aspects of AD. However, many AS-lncRNAs implicated in AD have not yet been comprehensively compiled and discussed. This paper reviews the role of AS-lncRNAs in neurodegenerative diseases, outlines their association with AD, and offers novel insights into the potential applications of antisense RNAs in the diagnosis and treatment of AD.

Cellular senescence is a complex process involving multiple factors, such as genetics, environment, and behavior. However, recent studies have shown that stress also plays a crucial role in inducing cellular senescence. Stress can affect cellular function and structure through various pathways, leading to accelerated aging. Exposure to stressful conditions can alter the neuroendocrine system, activate the hypothalamus-pituitary-adrenal axis and sympathetic adrenal medullary axis, and release cortisol and catecholamines, causing mitochondrial dysfunction, generating excessive reactive oxygen species, and inducing oxidative stress, DNA damage, and inflammatory reactions, ultimately resulting in accelerated cellular senescence. The process of stress-induced cellular senescence has been implicated in a number of chronic diseases, including age-related macular degeneration, chronic kidney disease, type 2 diabetes, cardiovascular disease and obstructive sleep apnea. In this review, we integrate recent progress research progress in our understanding of the mechanisms of stress-induced cellular senescence and discuss its underlying mechanisms from the perspective of stress hormones. We review potential therapeutic targets for stress-induced premature senescence and discuss the advantages and limitations of existing pharmacological agents capable of ameliorating stress-induced premature senescence.

Stroke, a leading cause of death and disability, often results from ischemic events that cut off the brain blood flow, leading to neuron death. Despite treatment advancements, survivors frequently endure lasting impairments. A key focus is the ischemic penumbra, the area around the stroke that could potentially recover with prompt oxygenation; yet its monitoring is complex. Recent progress in bioluminescence-based oxygen sensing, particularly through the Green enhanced Nano-lantern (GeNL), offers unprecedented views of oxygen fluctuations in vivo. Utilized in awake mice, GeNL has uncovered hypoxic pockets within the cerebral cortex, revealing the brain's oxygen environment as a dynamic landscape influenced by physiological states and behaviors like locomotion and wakefulness. These findings illuminate the complexity of oxygen dynamics and suggest the potential impact of hypoxic pockets on ischemic injury and recovery, challenging existing paradigms and highlighting the importance of microenvironmental oxygen control in stroke resilience. This review examines the implications of these novel findings for stroke research, emphasizing the criticality of understanding pre-existing oxygen dynamics for addressing brain ischemia. The presence of hypoxic pockets in non-stroke conditions indicates a more intricate hypoxic scenario in ischemic brains, suggesting strategies to alleviate hypoxia could lead to more effective treatments and rehabilitation. By bridging gaps in our knowledge, especially concerning microenvironmental changes post-stroke, and leveraging new technologies like GeNL, we can pave the way for therapeutic innovations that significantly enhance outcomes for stroke survivors, promising a future where an understanding of cerebral oxygenation dynamics profoundly informs stroke therapy.

Aging is a complex biological process that involves multi-level structural and physiological changes. Aging is a major risk factor for many chronic diseases. The accumulation of senescent cells changes the tissue microenvironment and is closely associated with the occurrence and development of tissue and organ fibrosis. Fibrosis is the result of dysregulated tissue repair response in the development of chronic inflammatory diseases. Recent studies have clearly indicated that SIRT2 is involved in regulating the progression of fibrosis, making it a potential target for anti-fibrotic drugs. SIRT2 is a NAD⁺ dependent histone deacetylase, shuttling between nucleus and cytoplasm, and is highly expressed in liver, kidney and heart, playing an important role in the occurrence and development of aging and fibrosis. Therefore, we summarized the role of SIRT2 in liver, kidney and cardiac fibrosis during aging.