Cardiac aging, particularly cardiac cell senescence, is a natural process that occurs as we age. Heart function gradually declines in old age, leading to continuous heart failure, even in people without a prior history of heart disease. To address this issue and improve cardiac cell function, it is crucial to investigate the molecular mechanisms underlying cardiac senescence. This review summarizes the main mechanisms and key proteins involved in cardiac cell senescence. This review further discusses the molecular modulators of cellular senescence in aging hearts. Furthermore, the discussion will encompass comprehensive descriptions of the key drugs, modes of action and potential targets for intervention in cardiac senescence. By offering a fresh perspective and comprehensive insights into the molecular mechanisms of cardiac senescence, this review seeks to provide a fresh perspective and important theoretical foundations for the development of drugs targeting this condition.

The normal function of the mitochondria is crucial for most tissues especially for those that demand a high energy supply. Emerging evidence has pointed out that healthy mitochondrial function is closely associated with normal heart function. When these processes fail to repair the damaged mitochondria, cells initiate a removal process referred to as mitophagy to clear away defective mitochondria. In cardiomyocytes, mitophagy is closely associated with metabolic activity, cell differentiation, apoptosis, and other physiological processes involved in major phenotypic alterations. Mitophagy alterations may contribute to detrimental or beneficial effects in a multitude of cardiac diseases, indicating potential clinical insights after a close understanding of the mechanisms. Here, we discuss the current opinions of mitophagy in the progression of cardiac diseases, such as ischemic heart disease, diabetic cardiomyopathy, cardiac hypertrophy, heart failure, and arrhythmia, and focus on the key molecules and related pathways involved in the regulation of mitophagy. We also discuss recently reported approaches targeting mitophagy in the therapy of cardiac diseases.

Aging is an intricate process involving interactions among multiple factors, which is one of the main risks for chronic diseases, including Alzheimer's disease (AD). As a member of cysteine protease, cathepsin S (CTSS) has been implicated in inflammation across various diseases. Here, we investigated the role of neuronal CTSS in aging and AD started by examining CTSS expression in hippocampus neurons of aging mice and identified a significant increase, which was negatively correlated with recognition abilities. Concurrently, we observed an elevation of CTSS concentration in the serum of elderly people. Transcriptome and fluorescence‐activated cell sorting (FACS) results revealed that CTSS overexpression in neurons aggravated brain inflammatory milieu with microglia activation to M1 pro‐inflammatory phenotype, activation of chemokine C‐X3‐C‐motif ligand 1 (CX3CL1)—chemokine C‐X3‐C‐motif receptor 1 (CX3CR1) axis and janus kinase 2 (JAK2)—signal transducer and activator of transcription 3 (STAT3) pathway. As CX3CL1 is secreted by neurons and acts on the CX3CR1 in microglia, our results revealed for the first time the role of neuron CTSS in neuron–microglia “crosstalk.” Besides, we observed elevated CTSS expression in multiple brain regions of AD patients, including the hippocampus. Utilizing CTSS selective inhibitor, LY3000328, rescued AD‐related pathological features in APP/PS1 mice. We further noticed that neuronal CTSS overexpression increased cathepsin B (CTSB) activity, but decreased cathepsin L (CTSL) activity in microglia. Overall, we provide evidence that CTSS can be used as an aging biomarker and plays regulatory roles through modulating neuroinflammation and recognition in aging and AD process.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with ~50 million people experiencing TBI each year. Ferroptosis, a form of regulated cell death triggered by iron ion-catalyzed and reactive oxygen species-induced lipid peroxidation, has been identified as a potential contributor to traumatic central nervous system conditions, suggesting its involvement in the pathogenesis of TBI. Alterations in iron metabolism play a crucial role in secondary injury following TBI. This study aimed to explore the role of ferroptosis in TBI, focusing on iron metabolism disorders, lipid metabolism disorders and the regulatory axis of system Xc⁻/glutathione/glutathione peroxidase 4 in TBI. Additionally, we examined the involvement of ferroptosis in the chronic TBI stage. Based on these findings, we discuss potential therapeutic interventions targeting ferroptosis after TBI. In conclusion, this review provides novel insights into the pathology of TBI and proposes potential therapeutic targets.

Diabetes mellitus is a global public health challenge with high morbidity. Type 2 diabetes mellitus (T2DM) accounts for 90% of the global prevalence of diabetes. T2DM is featured by a combination of defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. However, the pathogenesis of this disease is complicated by genetic and environmental factors, which needs further study. Numerous studies have demonstrated an epigenetic influence on the course of this disease via altering the expression of downstream diabetes-related proteins. Further studies in the field of epigenetics can help to elucidate the mechanisms and identify appropriate treatments. Histone methylation is defined as a common histone mark by adding a methyl group (-CH3) onto a lysine or arginine residue, which can alter the expression of downstream proteins and affect cellular processes. Thus, in tthis study will discuss types and functions of histone methylation and its role in T2DM wilsed. We will review the involvement of histone methyltransferases and histone demethylases in the progression of T2DM and analyze epigenetic-based therapies. We will also discuss the potential application of histone methylation modification as targets for the treatment of T2DM.

Diabetic cardiomyopathy (DCM), an important complication of diabetes mellitus (DM), is one of the most serious chronic heart diseases and has become a major cause of heart failure worldwide. At present, the pathogenesis of DCM is unclear, and there is still a lack of effective therapeutics. Previous studies have shown that the homeostasis of mitochondria and the endoplasmic reticulum (ER) play a core role in maintaining cardiovascular function, and structural and functional abnormalities in these organelles seriously impact the occurrence and development of various cardiovascular diseases, including DCM. The interplay between mitochondria and the ER is mediated by the mitochondria-associated ER membrane (MAM), which participates in regulating energy metabolism, calcium homeostasis, mitochondrial dynamics, autophagy, ER stress, inflammation, and other cellular processes. Recent studies have proven that MAM is closely related to the initiation and progression of DCM. In this study, we aim to summarize the recent research progress on MAM, elaborate on the key role of MAM in DCM, and discuss the potential of MAM as an important therapeutic target for DCM, thereby providing a theoretical reference for basic and clinical studies of DCM treatment.