Aging & Longevity

The most cutting-edge issue in the research on aging is the quest for biomarkers that transcend molecular and cellular domains to encompass organismal-level implications. We recently hypothesized the role of Autonomic Nervous System (ANS) imbalance in this context. Studies on ANS functions during aging highlighted an imbalance towards heightened sympathetic nervous system (SNS) activity, instigating a proinflammatory milieu, and attenuated parasympathetic nervous system (PNS) function, which...

The recent, controversial approval of antibody-based treatments for Alzheimer's disease (AD) is fueling a heated debate on the molecular determinants of this condition. The discussion should also incorporate a critical revision of the limitations of preclinical mouse models in advancing our understanding of AD. We critically discuss the limitations of animal models, stressing the need for careful consideration of how experiments are designed and results interpreted. We identify the shortcomings...

CONCLUSION: The depression in elderly patient should be reconsidered as a systemic disease, with coexisting major geriatric syndromes (disability, dementia, frailty) and combined pathogenetic mechanisms (metabolic syndrome, impaired renal function, low-grade inflammation, and allostatic load). Cortisol confirmed its role as principal mediator of the aging process in both dementia and metabolic syndrome.

Vaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of...

Crohn's disease (CD) is a complex and heterogeneous condition with no perfect preclinical model or cure. To address this, we explore adult stem cell-derived organoids that retain their tissue identity and disease-driving traits. We prospectively create a biobank of CD patient-derived organoid cultures (PDOs) from colonic biopsies of 53 subjects across all clinical subtypes and healthy subjects. Gene expression analyses enabled benchmarking of PDOs as tools for modeling the colonic epithelium in...

Although lifespan extension remains the gold standard for assessing interventions proposed to impact the biology of aging, there are important limitations to this approach. Our reanalysis of lifespan studies from multiple sources suggests that short lifespans in the control group exaggerate the relative efficacy of putative longevity interventions. Results may be exaggerated due to statistical effects (e.g. regression to the mean) or other factors. Moreover, due to the high cost and long...

Inbreeding depression has been documented in various fitness traits in a wide range of species and taxa, however, the mutational basis is not yet well understood. We investigate how putatively deleterious variation influences fitness and is shaped by individual ancestry by re-sequencing complete genomes of 37 individuals in a natural arctic fox (Vulpes lagopus) population subjected to both inbreeding depression and genetic rescue. We find that individuals with high proportion of homozygous loss...

Living longer and healthier boosts individual and family welfare. As part of the World Bank's Healthy Longevity Initiative, we quantified the economic value of achieving the highest possible life span. We estimated the economic value of reducing avoidable mortality, defined as the difference between observed (or projected) mortality and lowest achieved (or projected) mortality, by world regions, sex, and age, between 2000 and 2021, with projection to 2050. In 2019, 69% of mortality, or 40...

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.