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Marcus and Feldman's Osteoporosis, Fifth Edition, is the most comprehensive, authoritative reference on this disease. Led by a new editorial team, this fifth edition offers critical information on reproductive and hormonal risk factors, new therapeutics, ethnicity, nutrition, therapeutics, management and economics, comprising a tremendous wealth of knowledge in a single source not found elsewhere. Written by renowned experts in the field, this two-volume reference is a must-have for biomedical researchers, research clinicians, fellows, academic and medical libraries, and any company involved in osteoporosis drug research and development.

Age-related macular degeneration (AMD) was described for the first time in the 1840s and is currently the leading cause of blindness for patients over 65 years in Western Countries. This disease impacts the eye’s posterior segment and damages the macula, a retina section with high levels of photoreceptor cells and responsible for the central vision. Advanced AMD stages are divided into the atrophic (dry) form and the exudative (wet) form. Atrophic AMD consists in the progressive atrophy of the retinal pigment epithelium (RPE) and the outer retinal layers, while the exudative form results in the anarchic invasion by choroidal neo-vessels of RPE and the retina. This invasion is responsible for fluid accumulation in the intra/sub-retinal spaces and for a progressive dysfunction of the photoreceptor cells. To date, the few existing anti-AMD therapies may only delay or suspend its progression, without providing cure to patients. However, in the last decade, an outstanding number of research programs targeting its different aspects have been initiated by academics and industrials. This review aims to bring together the most recent advances and insights into the mechanisms underlying AMD pathogenicity and disease evolution, and to highlight the current hypotheses towards the development of new treatments, i.e., symptomatic vs. curative. The therapeutic options and drugs proposed to tackle these mechanisms are analyzed and critically compared. A particular emphasis has been given to the therapeutic agents currently tested in clinical trials, whose results have been carefully collected and discussed whenever possible.

Recent advances in microphysiological systems (MPS), also known as organs‐on‐a‐chip (OoC), enable the recapitulation of more complex organ and tissue functions on a smaller scale in vitro. MPS therefore provide the potential to better understand human diseases and physiology. To date, numerous MPS platforms have been developed for various tissues and organs, including the heart, liver, kidney, blood vessels, muscle, and adipose tissue. However, only a few studies have explored using MPS platforms to unravel the effects of aging on human physiology and the pathogenesis of age‐related diseases. Age is one of the risk factors for many diseases, and enormous interest has been devoted to aging research. As such, a human MPS aging model could provide a more predictive tool to understand the molecular and cellular mechanisms underlying human aging and age‐related diseases. These models can also be used to evaluate preclinical drugs for age‐related diseases and translate them into clinical settings. Here, we provide a review on the application of MPS in aging research. First, we offer an overview of the molecular, cellular, and physiological changes with age in several tissues or organs. Next, we discuss previous aging models and the current state of MPS for studying human aging and age‐related conditions. Lastly, we address the limitations of current MPS and present future directions on the potential of MPS platforms for human aging research. Age is one of the risk factors for many diseases, and enormous interest has been devoted to aging research. A human aging model using microphysiological systems (MPS) can provide a predictive tool to understand the molecular and cellular mechanisms underlying the human aging process and age‐related diseases. Here, we provide a review on the application of MPS in aging research.

INTRODUCTION Despite extensive studies on mixed neuropathologies, data from China are limited. This study aims to fill this gap by analyzing brain samples from Chinese brain banks. METHODS A total of 1142 brains from six Chinese brain banks were examined using standardized methods. Independent pathologists conducted evaluations with stringent quality control. Prevalence and correlations of neurological disorders were analyzed. RESULTS Significant proportions of brains displayed primary age‐related tauopathy (PART, 35%), limbic‐predominant age‐related TDP‐43 encephalopathy (LATE, 46%), and aging‐related tau astrogliopathy (ARTAG, 12%). Alzheimer's disease neuropathological change (ADNC, 48%), Lewy body disease (LBD, 13%), and cerebrovascular disease (CVD, 63%) were also prevalent, often co‐occurring with regional variations. CVD emerged as the potential most early contributor to neuropathological changes. DISCUSSION This analysis highlights the prevalence of PART, LATE, ARTAG, ADNC, LBD, and CVD, with regional differences. The findings suggest CVD may be the earliest contributing factor, potentially preceding other neuropathologies. Highlights The prevalence of primary age‐related tauopathy (PART), limbic‐predominant age‐related TDP‐43 encephalopathy (LATE), aging‐related tau astrogliopathy (ARTAG), Alzheimer's disease neuropathologic change, Lewy body disease, and cerebrovascular disease (CVD) in China, increasing with age, is comparable to other countries. Significant regional differences in the prevalences of diseases are noted. CVD develops prior to any other disorders, including PART, LATE, and ARTAG.

The human retinal pigment epithelium (RPE) and choroid are complex tissues that provide crucial support to the retina. Disease affecting either of these supportive tissues can lead to irreversible blindness in the setting of age-related macular degeneration. In this study, single-cell RNA sequencing was performed on macular and peripheral regions of RPE-choroid from 7 human donor eyes in 2 independent experiments. In the first experiment, total RPE/choroid preparations were evaluated and expression profiles specific to RPE and major choroidal cell populations were identified. As choroidal endothelial cells represent a minority of the total RPE/choroidal cell population but are strongly implicated in age-related macular degeneration (AMD) pathogenesis, a second single-cell RNA-sequencing experiment was performed using endothelial cells enriched by magnetic separation. In this second study, we identified gene expression signatures along the choroidal vascular tree, classifying the transcriptome of human choriocapillaris, arterial, and venous endothelial cells. We found that the choriocapillaris highly and specifically expresses the regulator of cell cycle gene (RGCC), a gene that responds to complement activation and induces apoptosis in endothelial cells. In addition, RGCC was the most up-regulated choriocapillaris gene in a donor diagnosed with AMD. These results provide a characterization of the human RPE and choriocapillaris transcriptome, offering potential insight into the mechanisms of choriocapillaris response to complement injury and choroidal vascular disease in age-related macular degeneration.

INTRODUCTION The presence and interaction of multiple comorbid neuropathologies are a major contributor to the worldwide dementia burden. METHODS We analyzed 1183 subjects from the National Alzheimer's Coordinating Center dataset with various combinations of isolated and mixed neurodegenerative pathologies and conducted mixed‐effects multiple linear regression modeling to comprehensively compare the neurocognitive and neuropsychological trajectories between groups over time. RESULTS In combination with Alzheimer's disease neuropathologic change, various combinations of limbic‐predominant age‐related transactive response DNA‐binding protein 43 encephalopathy, Lewy body dementia, and cerebrovascular disease further impair global cognition and specific neurocognitive domains; however, they do not appear to extensively affect the rate of decline with time across these domains, suggesting an additive but not synergistic effect. DISCUSSION These findings corroborate the known cumulative effects of mixed pathologies on cognition and add nuance to our understanding of their specific interactions, which is crucial for the development of biomarkers and effective therapeutics. Highlights Mixed neurodegenerative pathologies are common in the elderly population. The most common neurodegenerative pathologies were Alzheimer's disease neuropathologic change (ADNC), cerebrovascular disease (CVD), Lewy body dementia (LBD), and limbic‐predominant age‐related transactive response DNA‐binding protein 43 encephalopathy (LATE). The addition of various combinations of comorbid CVD, LBD, and LATE to ADNC worsened overall performance on cognitive and neuropsychological testing across time. In general, the addition of multiple comorbid neurodegenerative pathologies did not influence the rate of decline across the evaluated time period.

Four decades of the National Institute on Aging's sponsored research into Alzheimer's disease (AD) have resulted in symptomatic and mechanistic therapies, lifestyle interventions, increased understanding of genetic factors and protein misfolding, and descriptions of non‐AD neuropathological entities that mimic AD clinical symptoms. This is an overview of contributions from one of the original ten Alzheimer Disease Research Centers (ADRCs), the University of Kentucky ADRC. We celebrate 40 years of helping the field to define early pathogenetic mechanisms underlying transitions from normal cognitive aging to impairment in our elderly community‐based cohort, increased appreciation of the heterogeneity and multiple pathologies that characterize late‐life dementia, strategies for therapeutic intervention, and novel statistical approaches. We also highlight our educational efforts to train the workforce of the future and our long‐standing community outreach and partnerships. Highlights The University of Kentucky Alzheimer's Disease Research Center (UK‐ADRC) is an experienced and collaborative center celebrating its 40th year of National Institute on Aging funding in 2025. Our long‐standing community‐based cohort of motivated older adult volunteers and strong neuropathology program support the rationale for our overarching theme: “Transitions from Normal to Late‐Life Multi‐Etiology Dementia.” The UK‐ADRC's focus on normal aging and early cognitive transitions has been central to elucidating pathogenic mechanisms underlying transitions from normal cognitive aging to impairment and defining the heterogeneity and multiple pathologies that characterize late‐life dementia. UK‐ADRC infrastructure and resources support and create new opportunities for innovative and inclusive research, clinical programs across the cognitive continuum, educational and training opportunities, and community and national partnerships.

Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.

Aging is a major risk factor for most chronic disorders, for which cellular senescence is one of the central hallmarks. Senescent cells develop the pro‐inflammatory senescence‐associated secretory phenotype (SASP), which significantly contributes to organismal aging and age‐related disorders. Development of senotherapeutics, an emerging class of therapeutic agents to target senescent cells, allows to effectively delay aging and alleviate chronic pathologies. Here we report preliminary outputs from screening of a natural medicinal agent (NMA) library for senotherapeutic candidates and validated several agents with prominent potential as senomorphics. Rutin, a phytochemical constituent found in a number of plants, showed remarkable capacity in targeting senescent cells by dampening expression of the full spectrum SASP. Further analysis indicated that rutin restrains the acute stress‐associated phenotype (ASAP) by specifically interfering with the interactions of ATM with HIF1α, a master regulator of cellular and systemic homeostasis activated during senescence, and of ATM with TRAF6, part of a key signaling axis supporting the ASAP development toward the SASP. Conditioned media produced by senescent stromal cells enhanced the malignant phenotypes of prostate cancer cells, including in vitro proliferation, migration, invasion, and more importantly, chemoresistance, while rutin remarkably downregulated these gain‐of‐functions. Although classic chemotherapy reduced tumor progression, the treatment outcome was substantially improved upon combination of a chemotherapeutic agent with rutin. Our study provides a proof of concept for rutin as an emerging natural senomorphic agent, and presents an effective therapeutic avenue for alleviating age‐related pathologies including cancer. Senescent cells in solid organs are a major driving force of chronological aging and various age‐related pathologies. In the early stage of the SASP development (ASAP), ATM physically interacts with HIF1a and TRAF6. Rutin, a natural phytochemical agent, can impede the interaction between ATM and HIF1a or TRAF6. Through effectively suppressing the SASP development, rutin holds a substantial value to serve as a novel senomorphic agent in future clinics.

Organismal ageing is a complex process driving progressive impairment of functionality and regenerative potential of tissues. Cellular senescence is a state of stable cell cycle arrest occurring in response to damage and stress and is considered a hallmark of ageing. Senescent cells accumulate in multiple organs during ageing, contribute to tissue dysfunction and give rise to pathological manifestations. Senescence is therefore a defining feature of a variety of human age‐related disorders, including cancer, and targeted elimination of these cells has recently emerged as a promising therapeutic approach to ameliorate tissue damage and promote repair and regeneration. In addition, in vivo identification of senescent cells has significant potential for early diagnosis of multiple pathologies. Here, we review existing senolytics, small molecules and drug delivery tools used in preclinical therapeutic strategies involving cellular senescence, as well as probes to trace senescent cells. We also review the clinical research landscape in senescence and discuss how identifying and targeting cellular senescence might positively affect pathological and ageing processes. Graphical Abstract This article reviews the broad topic of cellular senescence, how to manipulate it ‐ novel probes and nanocarriers have potential diagnostic and therapeutic values ‐ and details a number of senotherapies that entered clinical trials.