Aging & Longevity

Due to aging, the efficiency of kidney function begins to decrease. Dysfunction in mitochondria and their cristae is a hallmark of aging. Therefore, age-related decline in kidney function could be attributed to changes in mitochondrial ultrastructure, increased reactive oxygen species, and alterations in metabolism and lipid composition. We sought to understand how mitochondrial ultrastructure is altered over time in tubular kidney cells. A serial block face-scanning electron microscope and...

CONCLUSION: A territorial geriatric hotline integrated into local professional healthcare networks is feasible and widely utilized, as reflected by the overall call volume. It facilitates rapid access to geriatric expertise and, based on the analysis of calls with complete data, may contribute to improving patient orientation, and to proposing alternatives to emergency department transfers. However, the study design did not allow for the systematic evaluation of the clinical outcomes associated...

CONCLUSIONS: The findings indicate that if government administrators and platform developers want to implement effective SCSP development and promotion strategies, they need to pay attention to improving older adults' digital literacy, optimizing the platform's information, system, and service quality, and strengthening external publicity to enhance the platforms' social influence.

Memory decline, particularly in neurodegenerative disorders such as Alzheimer's disease, represents a critical global public health challenge, with projections exceeding 150 million cases by 2050. Current therapeutic options remain limited: while drugs like donepezil and memantine offer symptomatic relief, and newer agents like lecanemab show modest effects on slowing progression, no disease-modifying cures exist. This underscores the urgent need to refine preclinical models bridging discovery...

Modern humans now routinely survive to advanced ages, in far greater proportions than ancestral populations, and thus experience the consequences of molecular pathways optimized for youth yet still active in old age. Natural selection weakens over the course of adulthood, creating a selection 'shadow' in which deleterious late-acting mutations accumulate and alleles with early-life benefits persist despite late-life costs. An evolutionary lens helps us to understand puzzling patterns - from...

Aging has effects on the immune system that are similar in men and women, but also reshapes their immune systems in unique, sex-specific ways. These sex-specific patterns of immune aging influence disease susceptibility, vaccine effectiveness, cancer survival, and responses to pharmacological therapies, and have direct implications for preventive medicine and clinical care. However, these differences in susceptibilities and responses are rarely considered in research, clinical trials, or...

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Defective proteostasis is a hallmark of aging cells and tissues. Among the different components of the proteostasis network, in this study, we focus on a selective form of autophagy known as chaperone-mediated autophagy (CMA), and we set out to understand its physiological role in the retina. Using mice deficient for CMA [knockout for lysosome-associated membrane protein type 2A (Lamp2A)], we have found that CMA blockade leads to impaired visual function, altered retinal proteostasis, and...

Cognitive dysfunction is an increasingly recognized complication of diabetes, contributing substantially to morbidity in the aging population, yet disease-modifying therapies remain scarce. Dietary intervention, a cornerstone of diabetes management, may offer neuroprotective potential. Low-carbohydrate ketogenic diets (LCKDs), typically restricting carbohydrates to < 50 g/day, effectively improve glycemic control and metabolic health. Emerging preclinical and clinical evidence suggests that...

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Aging is characterized by progressive loss of physiological resilience accompanied by increased susceptibility to chronic diseases. Among the interconnected hallmarks of aging, cellular senescence has emerged as a central driver of systemic inflammation through the senescence-associated secretory phenotype (SASP). Senescent cells accumulate across multiple tissues with advancing age and secrete complex mixtures of cytokines, growth factors, and proteases that reshape tissue microenvironments and...

Heart failure with preserved ejection fraction (HFpEF) is a cardiometabolic syndrome strongly associated with aging, systemic inflammation and endothelial dysfunction, in which impaired endothelial nitric oxide synthase (eNOS) signaling plays a central role. This study aimed to identify circulating proteins associated with HFpEF and to explore their relationship with endothelial alterations under metabolic stress. A total of 109 HFpEF patients and 49 control subjects underwent clinical,...

CONCLUSIONS: Perceived age-based discrimination is associated with increased healthcare utilization among older adults in India through both direct and indirect pathways, with the indirect effect operating via probable depression and subsequent multimorbidity. These findings highlight the importance of addressing discrimination and integrating mental health within primary care, while also accounting for rural-urban disparities, to promote equitable healthcare access and improve health outcomes...

Aging is a major independent risk factor for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, effective therapeutic strategies for this population remain limited. Here, we established a model of aging-associated MASLD by subjecting aged mice to a long-term high-fat diet (HFD), which recapitulated key disease features including progressive hepatic steatosis, inflammation, insulin resistance, and fibrosis. A 6-week exercise intervention...

FAM162A is an inner mitochondrial protein known for its role in hypoxia-induced apoptosis. However, it is often overexpressed in cancer, where its pro-apoptotic function appears to be overridden, suggesting novel unknown roles in mitochondrial function and cell survival. Furthermore, its precise localization, topology, and orientation remain controversial. In this study, we aimed to assess the role of FAM162A in mitochondrial structure, dynamics, and bioenergetics and its impact on cellular and...

CONCLUSIONS: These findings support the conclusion that somatic symptoms may disproportionately inflate depression scores among patients with ovarian cancer at diagnosis, which may potentially lead to misclassification or overestimation of depression severity. This highlights the need for refined measurement approaches that account for the somatic burden of cancer in assessing depression during active disease.

Interpreting genome-wide epigenomic experiments, such as DNA methylation profiling and chromatin accessibility assays, requires tools that can identify which regulatory programs underlie coordinated changes across genomic regions. Without this regulatory context, lists of differential regions remain largely descriptive and difficult to interpret mechanistically. Existing approaches either apply hard significance cutoffs that discard moderate but biologically meaningful signals, or rely on...

Variability in Alzheimer's disease (AD) clinical presentation complicates mechanistic studies and therapeutic outcome prediction. Brain protein aggregate load does not directly correlate with clinical symptoms; however, different subtypes of AD have been reported to exhibit structural variation (polymorphism) of aggregates. Little is known about the structural diversity of the deposits in cognitively normal aged brains. This study investigates the structural heterogeneity of amyloid aggregates...

Nucleocytoplasmic transport is a central but underappreciated component of the proteostasis network as it controls the trafficking and partitioning of proteins between the nucleus and cytoplasm through the nuclear pore complex (NPC). Transport of large proteins across the NPC is mediated by karyopherins, a conserved family of importins and exportins that function through a Ran GTPase-dependent cycle. Beyond their canonical transport activities, karyopherins can directly contribute to...