Aging & Longevity

While BAG3 has been identified as a causative gene for dilated cardiomyopathy, the major pathological events in BAG3-related cardiomyopathy that could be targeted for therapeutic benefit remain to be discovered. Here, we aim to uncover novel pathological events through genetic studies in a zebrafish bag3 cardiomyopathy model. Given the known cardioprotective effects of mtor inhibition and the fact that transcription factor EB (tfeb) encodes a direct downstream phosphorylation target of mTOR...

Epigenetic clocks have emerged as promising biomarkers of aging, but their responsiveness to lifestyle interventions and relevance for short-term changes in cardiometabolic health remain uncertain. In this study, we examined the associations between three epigenetic aging measures (DunedinPACE, PCPhenoAge acceleration, and PCGrimAge acceleration) and a broad panel of cardiometabolic biomarkers in 144 obese participants from the MACRO trial, a 12-month weight-loss dietary intervention comparing...

Immune checkpoint inhibitors (ICIs) can re-active the immune response and induce a complete response in mismatch repair-deficient and microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, most CRCs exhibit proficient mismatch repair and microsatellite stable (pMMR/MSS) phenotypes with limited immunotherapy response because of sparse intratumoral CD8^(+) T-lymphocyte infiltration. Cellular senescence has been reported to involve immune cell infiltration through a...

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The meninges, consisting of the dura, arachnoid and pia mater that surround the brain and spinal cord, have been recognized from the earliest anatomical studies. First identified in 1787, lymphatic vessels in the dura are now receiving greater attention as their contribution to cerebrospinal fluid (CSF) clearance in diverse neurological conditions is being investigated. New methods have increased the understanding of dural lymphatics, but much is still being learned about their heterogeneity,...

Ashwagandha (Withania somnifera), a revered herb in Ayurvedic medicine, has gained significant scientific recognition for its potential to promote healthy aging. Traditionally used as a Rasayana or rejuvenator, this potent adaptogen helps the body manage stress and enhance vitality. This review synthesises extensive evidence for its multifaceted anti-aging capabilities, which target key hallmarks of the aging process. The mechanisms underpinning its effects include enhancing telomerase activity...

NT-proBNP levels increase exponentially with age and are associated with cardiovascular and all-cause mortality. From NT-proBNP concentration a surrogate for biological age ("proBNPage") can be obtained. The primary objective of this study was to define a method to design future trials on anti-aging treatments using proBNPage. The secondary objective was the tentative evaluation of 4 potential anti-aging dietary supplements. The trial lasted 2 years and involved 120 healthy subjects aged 71.7 ±...

CONCLUSIONS: Implementing regular televisits in the nursing home setting reduced the number of hospital admissions. This is most likely due to more frequent medical assessment, enabling early detection and timely management of deteriorations. By preventing unnecessary hospital admissions residents were spared the physical and psychological burdens connected with emergency transfers and protected from hospital-associated risks. On top of enhancing quality of care for the residents, televisits...

INTRODUCTION: Alzheimer's Disease (AD) is a common neurodegenerative disease among the elderly population. It has been posited that the onset and progression of AD are influenced by a combination of various factors. Occlusal support loss due to tooth loss has been reported to be a risk factor triggering cognitive dysfunction. This study aimed to investigate the relationship between tooth loss and cognitive dysfunction and illustrate the role of pyroptosis in advancing Alzheimer's disease.

Ageing is one of the most significant risk factors for heart disease; however, it is still not clear how the human heart changes with age. Taking advantage of a unique set of pre-mortem, cryopreserved, non-diseased human hearts, we performed omics analyses (transcriptomics, proteomics, metabolomics, and lipidomics), coupled with biologically informed computational modelling in younger (≤ 25 years old) and older hearts (≥ 50 years old) to describe the molecular landscape of human cardiac ageing....

Almost half of pregnant women globally are currently estimated to be overweight or obese. Rates of childhood obesity are also on the rise, in part because of increased consumption of dietary saturated fats. However, the long-term effect of peri- and postnatal high fat (HF) feeding on cognitive function and neuronal expression has not yet been investigated. Male and female C57BL/6J mice born to dams fed a control (C) or high fat (HF) diet were themselves fed either the C or HF diet, generating...

Cell states evolve through the combined activity of signaling pathways and gene networks. While transcription factors can direct cell fate, these factors rely on a receptive cell state. How signaling levels contribute to the emergence of receptive cell states remains poorly defined. Using a well-defined model of direct conversion, we examined how levels of the mitogen-activated protein kinase (MAPK)-activating oncogene HRAS^(G12V) influence direct conversion of primary fibroblasts to induced...

The physiological decline associated with aging is often accompanied by a progressive deterioration in cognitive processing abilities driven by a series of cellular dysfunctions that remain poorly understood. In the hippocampus, a critical area for learning and memory, aging affects the functional expression of ionotropic and metabotropic receptors, including the metabotropic glutamate receptors (mGluRs). mGluRs play a critical role in multiple cellular functions, including modulation of ion...

Visual motion perception declines during natural aging in most animals including humans. Edible berries of blackcurrant (BC) and its extracted anthocyanins (BCAs) have beneficial effects on human eyes. However, the effect of BCAs on the perception of moving objects and other dynamic visual patterns remains unknown. In the current study, we investigated whether BCAs improve visual movement perception in aging mice. The aging mice were fed either a standard diet or a standard diet containing BC....

CONCLUSIONS: Co-occurrence of low IC and frailty was significantly associated with poor self-rated health. These findings suggest that considering IC and frailty may enhance understanding of self-rated health in later life.

CONCLUSIONS: The points-program has the potential to promote not only the immediate outcomes it targets but also other domains of health and well-being outcomes through increased social interaction and healthy behaviors.

Human hematopoietic stem and progenitor cell (HSPC) fitness declines following exposure to stressors that reduce survival, dormancy, telomere maintenance, and self-renewal, thereby accelerating aging. While previous National Aeronautics and Space Administration (NASA) research revealed immune dysfunction in low-earth orbit (LEO), the impact of spaceflight on human HSPC aging had not been studied. To study HSPC aging, our NASA-supported Integrated Space Stem Cell Orbital Research (ISSCOR) team...

Sodium-glucose cotransporter-2 inhibitors have been proposed as caloric restriction mimetics with potential anti-aging effects. However, clinical data on their influence on aging biomarkers are limited. In this multicenter, randomized, double-blind, placebo-controlled trial, 150 participants with type 2 diabetes are randomized (1:1) to receive oral henagliflozin (10 mg/day) or placebo for 26 weeks. Compared with placebo, henagliflozin significantly increases telomere length (primary endpoint),...

Nuclear insertions of mitochondrial DNA (mtDNA) segments (NUMTs) represent an evolutionarily conserved phenomenon originating from the ancient endosymbiotic relationship between mitochondria and host cells. These insertions predominantly localize near intergenic or regulatory regions and are often enriched in tissues with high metabolic activity. Once regarded as inert pseudogenes or genomic artifacts, NUMTs are now recognized as dynamic elements capable of modulating nuclear architecture and...

Calcium (Ca^(2+))/calmodulin (CaM)-dependent protein kinase II (CaMKII) is an emerging drug target for age-related diseases. It is a multifunctional kinase with complex activation modes, numerous isoforms, broad tissue distribution, and a dual role in health and disease. In particular, its isoforms share a high degree of conservation within the catalytic and regulatory domains, with only minor differences confined to the linker region. These characteristics of CaMKII make the development of...