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CONCLUSIONS AND IMPLICATIONS: HGS asymmetry was associated with an increased risk of frailty, comorbidities, and mortality in subsequent years. More attention should be paid to dominant HGS asymmetry when predicting adverse health conditions and mortality.

Measuring biological age typically requires invasive and costly procedures. To address this, the MoveIt! Age Score was developed: a simple, scalable, and interpretable aging clock that predicts biological age using only wearable-derived steps data. MoveIt! Age was trained on steps data from the United States National Health and Nutrition Examination Survey (NHANES), using chronological age, maximum step count, and step count variability to predict PhenoAge, a blood biochemistry biological age...

High-resolution structure determination of ex vivo amyloid fibrils offers critical mechanistic insights into amyloid polymorphism and heterogeneity of neurodegenerative diseases. However, purifying amyloid fibrils from diseased brains may favor certain polymorphs over others. Here, instead of purifying fibrils, we used in situ amplification (ISA) of α-synuclein (α-syn) fibrils in brain homogenates. Cryoelectron microscopy (cryo-EM) structural analysis of the ISA fibrils from patients with...

While immune system involvement in aging is increasingly recognized, causal relationships between specific immune cell populations and biological aging indicators remain unclear. We aimed to identify immune targets influencing aging trajectories to inform future immunomodulatory interventions. We conducted two-sample Mendelian randomization (MR) analysis using immunophenotype GWAS data (3,757 Sardinian participants) and aging phenotype statistics (PhenoAgeAccel: n = 107,460; BioAgeAccel: n =...

Loss of regeneration is a key feature of aging organs, often linked to stem cell exhaustion. Skeletal muscle stem cells (MuSCs) undergo age-related numerical and functional decline, contributing to reduced regenerative potential. Using low-input multi-omics, we systematically profiled the epigenome, transcriptome, and 3D genome of MuSCs from individual mice across 3 age groups (young, old, and geriatric) and both sexes. At baseline, young male MuSCs showed reduced expression of cell...

Sarcopenia, characterized by decreased skeletal muscle mass and strength, is classified as "primary" (due to aging) or "secondary" (due to diseases). MicroRNA-22-3p (miR-22) regulates muscle differentiation and function. We assessed the diagnostic value of circulating miR-22 levels in patients with primary and secondary sarcopenia. miR-22 levels were evaluated in 61 older adults from the "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) study and...

CONCLUSION: Depression has a substantial negative effect on the quality of life of older adults, while death anxiety shows no significant impact. These psychological issues, particularly depression, are widespread in the older adult population, and with an aging population, addressing mental health issues is becoming increasingly crucial to ensuring the quality of life for older adults. Future studies should further explore the complex dynamics between these factors to guide effective...

Age-dependent exhaustion of endogenous stem cell pools-and the resulting decline in tissue regeneration and homeostatic maintenance-is a hallmark of organismal aging and age-related pathology. In a study published in Cell, Liu and collaborators engineered human ESC-derived mesenchymal progenitor cells to give the ability to resist senescence, environmental stress, and malignant transformation.

The liver is one of the organs most affected by alcohol consumption, and its interaction with aging is particularly significant. Chronic alcohol consumption accelerates liver aging through mechanisms such as oxidative stress, inflammation, fibrosis, and impaired regeneration. It is still unknown whether senescent cell clearance orchestrates innate and adaptive immune responses during the alcohol-induced old liver damage process. To investigate this, we used INK-ATTAC transgenic mice treat with...

CONCLUSIONS: The findings of this study indicate that HNC in the care of older adults is influenced by ethical competencies, attitudes towards aging, professional training, and work-related environmental factors. Therefore, developing structured in-service training programs, promoting ethical conduct in nursing, and reducing ageist attitudes are considered effective strategies for enhancing HNC. The results of this research can inform policies in nursing education and human resource development.

Recent studies at molecular and genomic scales have enriched our understanding of life's most fundamental building block: the cell. However, bridging the gap between single-cell phenotypes and the emergent functions of tissues and organs remains a formidable challenge. Here, we suggest that the conceptual span from cells to tissues and organs is so large as to warrant intermediate stepping stones. Drawing inspiration from "network motifs"-discrete units of cell-level function that emerge from...

Aging is a complex process that leads to various pathologies and poses a significant socioeconomic challenge. Stem cell therapies offer a promising avenue for intervention, primarily through mechanisms like telomere maintenance and cellular rejuvenation. However, conventional stem cell sources often come with limitations such as invasive collection, ethical concerns, safety risks, and high costs, which impede their clinical application. Urine-derived stem cells (USCs), in contrast, present an...

During aging, peripheral nerves undergo structural and cellular changes that trigger loss of function, impair quality of life, and increase disease risk. During peripheral nerve aging there are cellular and molecular changes, such as increased extracellular matrix deposition. The mechanisms behind these aging-induced alterations remain unclear. Here, we profile mouse sciatic nerves using single nucleus transcriptomics and unravel changes in macrophage subtypes during nerve aging. Phagocytic...

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, with limited treatments. Gene therapy offers an alternative strategy for treating a large portion of ALS patients, however, the disparate genetic alterations in ALS complicate the development of gene therapies. Tyrosine receptor kinase B (TRKB) and Tyro3 receptors are highly expressed in mouse spinal cord motor neurons, suggesting that their ligands, brain-derived neurotrophic factor (BDNF) and growth arrest-specific 6...

Homeostatic systems (nervous, immune, and endocrine) are crucial for maintaining health throughout life and, consequently, relevant for the rate of aging and the longevity achieved. In many species, male and female mammals show different lifespans, attributed to distinct redox states, but it is scarcely known whether sex differences in the functioning of these systems are involved. This study investigated, in an integrative view, sex differences in the nervous and immune systems of Swiss strain...

Chronic conditions and multimorbidity are increasingly prevalent in ageing populations, and their impact on disability remains poorly understood. This study investigated the association of chronic conditions and multimorbidity at ages 50, 60, 70, and 80 years with the subsequent onset of disability. Data from 108,810 participants (54% women, mean age 61.2 ± 9.8 at baseline) from the Health and Retirement Study, the English Longitudinal Study of Ageing, and the Survey of Health, Ageing, and...

The p38 mitogen-activated protein kinase has a well-characterized role in modulation of inflammatory processes throughout the body. In the central nervous system, p38 is primarily studied within neurons and microglia, most commonly in the context of neurological insult. The present study was designed to determine its function in astrocytes during non-pathological aging. We generated a conditional knockout model in which a tamoxifen-inducible Aldh1l1 promoter drives Cre recombinase expression in...

Mitochondrial dysfunction is a hallmark of Parkinson's disease (PD), but the mechanisms by which it drives autosomal dominant and idiopathic forms of PD remain unclear. To investigate this, we generated and performed a comprehensive phenotypic analysis of a knock-in mouse model carrying the T61I mutation in the mitochondrial protein CHCHD2 (coiled-coil-helix-coiled-coil-helix domain-containing 2), which causes late-onset symptoms indistinguishable from idiopathic PD. We observed pronounced...

The extrafollicular (EF) B cell differentiation pathway has emerged as a prominent source of autoantibody-secreting cells (ASCs) in systemic lupus erythematosus (SLE). CD21^(lo)CD11c^(+) B cells are associated with aging, infection, and autoimmunity. They are key contributors to EF ASCs, yet their developmental trajectory and receptor programming are unclear. To study EF mechanics of autoreactive B cells, we adoptively transferred naïve B cell populations into 564Igi mice, which act as an...

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) offers a regenerative strategy for heart repair, but efficiency declines in adult and aged cells. Transcriptomic and epigenetic profiling identified cellular senescence as a major barrier limiting cardiac fibroblast (CF) plasticity and cardiogenic conversion. Postneonatal fibroblasts exhibited impaired activation of cardiac gene programs and persistent expression of fibrotic and inflammatory signatures. A loss-of-function...