Aging & Longevity

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Microglia are the resident macrophages of the central nervous system¹. In mice, microglia seed the brain during embryogenesis and can be maintained throughout life with minimal input from adult haematopoiesis^(2-4). The origins of human microglia are less clear, but recent evidence suggests that bone-marrow-derived cells contribute to the human microglial pool in certain individuals^(5-9). Here, to investigate the ontogeny of human microglia, we develop an approach that uses the collection of...

Solution processing remains the dominant route to high-performance perovskite/silicon tandems, but it remains challenging to simultaneously achieve industrial scalability and long-term reliability^(1-3). Thermal evaporation is more industrially viable, yet it has not been successfully demonstrated for large-area perovskite/silicon tandems, largely due to the thermal degradation of formamidinium iodide (FAI) during high-temperature evaporation. Here we synthesize a formamidinium-based eutectic...

Pharmacological glucagon-like peptide-1 receptor (GLP-1R) activation reduces food intake and is an effective therapy for type 2 diabetes and obesity¹. The use of GLP-1 medicines has revealed pleiotropic beneficial effects beyond glucose and weight control^(2-5), but little is known about the underlying basis of the pleiotropic effects. Here, treatment of 20-month-old female C57BL/6 mice with the GLP-1R agonist semaglutide for 3 months improved physiological function, attenuated hallmarks of...

Chemotherapy-induced bone loss represents a major clinical challenge, particularly in aging populations, yet the contribution of cellular senescence to this process and its therapeutic potential remain incompletely understood. Here, we investigated the role of chemotherapy-induced cellular senescence in mediating skeletal deterioration following chemotherapy and evaluated the therapeutic potential of senolytic treatment. Young (3-month-old) and aged (20-month-old) male and female mice were...

Excessive alcohol consumption accelerates cardiovascular aging by promoting oxidative stress, inflammation, lipid dysregulation, fibrotic remodeling, and loss of ventricular-vascular reserve. PCSK9, a key regulator of cholesterol metabolism, has emerged as a mediator of age-related cardiovascular dysfunction and alcohol-associated liver and neurovascular injury. We investigated whether PCSK9 inhibition protects against alcohol-induced cardiovascular dysfunction and associated cardiac-hepatic...

Global life expectancy has risen since 1973 from 58 to over 73 years, while the share of people aged 65 years and older has doubled to 10% and is projected to reach 21% by 2073. This shift is linked to an epidemiological transition from infectious to chronic disease. Here, using Global Burden of Disease data, we reframe this transition by statistically grouping diseases on the basis of their impact over the life cycle, yielding four clusters: infant, early-adult, later-adult and aging-related....

Mutations and polymorphisms in the Rho guanine nucleotide exchange factor 10 (ARHGEF10) locus are associated with behavioral and locomotor dysfunctions in humans, including psychiatric disorders and polyneuropathies that show age- and sex-specific prevalence. ARHGEF10 encodes a conserved guanine exchange factor that activates Rho GTPases and has proposed roles in cell migration and adhesion, but the relevant cell types and mechanisms underlying its age- and sex-dependent effects remain unclear....

CONCLUSION: Consistent with the broader tele-neuropsychology literature, direct-to-home assessment is feasible and acceptable in older adults, with evidence indicating comparable test reliability to clinic standards. Embracing this practice model may promote greater support and access to neuropsychological assessment for older adults.

The absence of periodic atomic arrangement makes it difficult to detect microscopic defects in metallic glasses, yet their roles in macroscopic shape change are prominent. Motivated by probing defects mechanically, we perform stepwise tensile creep at ambient temperature on as-spun metallic-glass ribbons that show structural anisotropy in selected area electron diffraction. The main discovery is a non-linear strain response in which the segmentally added stress causes the creep strain to...

Actin is a highly conserved cytoskeletal protein that regulates numerous cellular processes essential for tissue homeostasis and healthy aging. Although genetic studies have established important roles for actin and actin-binding proteins in longevity, pharmacological approaches offer complementary advantages for manipulating conserved cytoskeletal pathways across model systems. Here, we systematically evaluated the effects of small-molecule modulators targeting distinct actin regulatory...

Dietary isoleucine restriction improves metabolic health and lifespan in animal models. It is hypothesized that shifts in branched-chain amino acid catabolism drive longevity. We investigated dietary isoleucine restriction on organismal branched-chain amino acid catabolism and its association with longevity and reproduction. In two main experiments, adult female Lubber grasshoppers were assigned to a high-quality diet (Bal ile) or diets with two levels of isoleucine content (moderate isoleucine...

Aging is a multifaceted process where physiological metrics, such as brain age and muscle age (MA), provide deeper insights than chronological age alone. These nonlinear trajectories are heavily influenced by exogenous factors like lifestyle and nutrition. In older populations, muscle age acceleration (MAA) critically impacts functional autonomy and cognitive health, necessitating research into its link with brain network organization to refine assessments and, based on these, integrated motor...

A key question in human neuroscience is to understand how individual differences in brain function relate to cognitive differences. However, the optimal condition of brain function to study between-person differences in cognition remains unclear. While many studies have developed objective biomarkers to accurately predict intelligence and general cognition, consensus on domain-specific markers has not yet emerged. Brain age has been proposed as a potential candidate, but recent research suggests...

Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the aging population globally. Although genome-wide association studies (GWAS) have identified many AMD susceptibility loci, the genes and mechanisms underlying many of these associations remain unresolved. Here, we integrated expression quantitative trait locus (eQTL) data with AMD GWAS to prioritize nine putative genes. Through in vivo screening in zebrafish, we demonstrated that the downregulation...

The Tabula Sapiens is a reference human cell atlas containing single-cell transcriptomic data from more than two dozen organs and tissues. Here, we report Tabula Sapiens 2.0, which includes data from nine new donors, doubles the number of cells, and adds four new tissues. These new data include four donors with multiple organs contributed, thus providing a unique dataset in which genetic background, age, and epigenetic effects are controlled for. We illustrate applications of the Tabula Sapiens...

Life satisfaction is a key component of successful aging. This study investigated the correlates of life satisfaction in a sample of 127 older adults (M(age) = 73.1 years, SD = 5.4) from Sardinia, an Italian island known for successful aging. Participants were assessed for global cognitive efficiency, perceived health, lifestyle habits, life satisfaction, and specific cognitive functions using the digital screening tool DIGICOG-MS. After controlling for age, education, and global cognitive...