Aging & Longevity

With population aging, national health systems face difficult trade-offs in allocating resources. The World Bank launched the Healthy Longevity Initiative to generate evidence for investing in policies that can improve healthy longevity and human capital. As part of this initiative, we quantified the economic value of reducing avoidable mortality from major noncommunicable diseases and injuries. We estimated avoidable mortality-the difference between lowest-achieved mortality frontiers and...

A decline in mitochondrial function is a hallmark of aging and neurodegenerative diseases. It has been proposed that changes in mitochondrial morphology, including fragmentation of the tubular mitochondrial network, can lead to mitochondrial dysfunction, yet the mechanism of this loss of function is unclear. Most proteins contained within mitochondria are nuclear-encoded and must be properly targeted to the mitochondria. Here, we report that sustained mRNA localization and co-translational...

MicroRNA plays a crucial role in post-transcriptional gene regulation and has recently emerged as a factor linked to aging, but the underlying regulatory mechanisms remain incompletely understood. In this study, we observed lifespan-extending effects in miR-80-deficient Caenorhabditis elegans at 20°C but not 25°C. At 20°C, miR-80 deletion leads to NLP-45 upregulation, which positively correlates to increased abu transcripts and extended lifespan. Supportively, we identified miR-80 binding...

Mesenchymal stromal cells (MSCs), also known as fibro-adipogenic progenitors, play a critical role in muscle maintenance and sarcopenia development. Although analogous MSCs are present in various tissues, recent single-cell RNA-seq studies have revealed the inter-tissue heterogeneity of MSCs. However, the functional significance of MSC heterogeneity and its role in aging remain unclear. Here, we investigated the properties of MSCs and their age-related changes in seven mouse tissues through...

Mitochondria are crucial organelles in maintaining cellular homeostasis. They are involved in processes such as energy production, metabolism of lipids and glucose, and cell death regulation. Mitochondrial dysfunction can lead to various health issues such as aging, cancer, neurodegenerative diseases, and chronic liver diseases. While mitophagy is the main process for getting rid of excess or damaged mitochondria, there are additional mechanisms for preserving mitochondrial quality. One such...

Aging is one of the most significant factors affecting cardiovascular health, with cellular senescence being a central hallmark. Senescent cells (SCs) secrete a specific set of signaling molecules known as the senescence-associated secretory phenotype (SASP). The SASP has a remarkable impact on age-associated diseases, particularly cardiovascular diseases (CVD). Targeting SCs through anti-aging therapies represents a novel strategy to effectively retard senescence and attenuate disease...

Senescence is a cell fate driven by different types of stress that results in exit from the cell cycle and expression of an inflammatory senescence-associated secretory phenotype (SASP). Here, we demonstrate that stable overexpression of miR-96-5p was sufficient to induce cellular senescence in the absence of genotoxic stress, inducing expression of certain markers of early senescence including SASP factors while repressing markers of deep senescence including LINE-1 and type 1 interferons....

The recent capability to measure thousands of plasma proteins from a tiny blood sample has provided a new dimension of expansive data that can advance our understanding of human health. For example, the company SomaLogic has developed the means to measure more than 10,000 proteins and Thermo Fisher's Olink assays over 5400 proteins from as little as 2 μl. When these rich data are integrated with other layers of information from large patient cohorts, such as the UK Biobank's genetic, health, and...

In Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum. Participants were assigned a Braak stage at baseline and followed for 1.97 (s.d. 0.62) years. NPS were investigated using the Mild Behavioral Impairment Checklist (MBI-C) and the Neuropsychiatric Inventory...

Many popular spatial transcriptomics techniques lack single-cell resolution. Instead, these methods measure the collective gene expression for each location from a mixture of cells, potentially containing multiple cell types. Here, we developed scResolve, a method for recovering single-cell expression profiles from spatial transcriptomics measurements at multi-cellular resolution. scResolve accurately restores expression profiles of individual cells at their locations, which is unattainable with...

Despite advancements in healthcare and increased lifespan, aging populations face numerous challenges, including declining cognitive function, increased susceptibility to chronic diseases, and reduced quality of life. This study investigated Aging impaired Locomotors and Biochemical Activities in Drosophila melanogaster Oregon R (Fruit Fly) Model with the aim to elucidate the mechanism involved. Adult wild-type Drosophila melanogaster Oregon R was used for this study. Survival assay, antioxidant...

CONCLUSION: Mitochondrial dysfunctions (decreased mtDNAcn, impaired mitochondrial morphology, imbalanced mitochondrial dynamic, impaired mitochondrial respiratory function, and increased ROS levels) were significantly correlated with frail status.

Long noncoding RNAs (lncRNAs) are increasingly appreciated for their important functions in mammalian cells. However, how their functional capacities are encoded in their sequences and manifested in their structures remains largely unknown. Some lncRNAs bind to and modulate the availability of RNA-binding proteins, but the structural principles that underlie this mode of regulation are unknown. The NORAD lncRNA is a known decoy for Pumilio proteins, which modulate the translation and stability...

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CONCLUSIONS: In addition to known barriers including lack of timely knowledge, service delays, and caregiver stress, Veteran-caregiver disagreements emerged as a novel barrier to using HCBS. A multi-pronged approach that addresses these barriers may increase timely access to HCBS.

The process of aging is a natural phenomenon characterized by gradual deterioration in biological functions and systemic homeostasis, which can be modulated by both genetic and environmental factors. Numerous investigations conducted on model organisms, including nematodes, flies, and mice, have elucidated several pivotal aging pathways, such as insulin signaling and AMPK signaling. However, it remains uncertain whether the regulation of the aging process is uniform or diverse across different...

Centenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models of human aging and resilience to disease that allow for the testing of potential interventions are virtually non-existent. We obtained and characterized over 96 centenarian and offspring peripheral blood samples including those connected to functional independence data highlighting resistance to disability and cognitive impairment. Targeted methylation arrays were used in...

The hair bundle, or stereocilia bundle, is the mechanosensory compartment of hair cells (HCs) in the inner ear. To date, most mechanistic studies have focused on stereocilia bundle morphogenesis, and it remains unclear how this organelle critical for hearing preserves its precise dimensions during life in mammals. The GPSM2-GNAI complex occupies the distal tip of stereocilia in the tallest row and is required for their elongation during development. Here, we ablate GPSM2-GNAI in adult mouse HCs...

Central tolerance of thymocytes to self-antigen depends on the medullary thymic epithelial cell (mTEC) transcription factor autoimmune regulator (Aire), which drives tissue-restricted antigen (TRA) gene expression. Vitamin D signaling regulates Aire and TRA expression in mTECs, providing a basis for links between vitamin D deficiency and autoimmunity. We find that mice lacking Cyp27b1, which cannot produce hormonally active vitamin D, display profoundly reduced thymic cellularity, with a reduced...