Aging & Longevity

Age-related decline in physical function is a hallmark of aging and a major driver of morbidity, disability, and loss of independence in older adults, yet the molecular processes linking muscle aging to functional deterioration remain incompletely defined. Emerging evidence implicates ferroptosis, defined as iron-dependent, lipid peroxidation-driven cell death, as a compelling but underexplored contributor to age-related muscle wasting and weakness. Although ferroptosis signatures appear in aged...

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β42 (Aβ42) neurotoxic peptides that cause oxidative stress and neurodegeneration. The current study examined the neuroprotective properties of salvianolic acid A (SalA), an antioxidant polyphenol, in a Drosophila melanogaster model of AD. Transgenic flies expressing human Aβ42 were assayed for eye morphology, life span, and locomotor function after SalA diet supplementation. RNA-seq and RT-qPCR were used to quantify...

CONCLUSIONS: In this nationally representative cohort, vision difficulty and motor impairments were independently associated with increased dementia risk over up to 11 years. The presence of multiple sensory difficulties and motor impairments substantially increased the risk of dementia, emphasizing the importance of their early detection and management to reduce dementia risk.

Working memory (WM) processes decline with increasing age. According to recent concepts, it is necessary to differentiate between dynamically changing 'WM states' which are regulated via gating mechanisms. We investigated which neural oscillatory processes underlying WM gating and updating are affected by age with a focus on alpha and theta band activity. With an EEG beamforming approach, we examined the data of N = 132 healthy individuals aged 18-76 years who performed the reference-back...

CONCLUSION: Texture analysis combined with machine learning could provide non-invasive biomarkers to classify muscles of young and old individuals, and assist in function prediction.

CONCLUSIONS AND IMPLICATIONS: Compared with married veterans, widowers had greater rates of cognitive decline, greater difficulty completing IADLs, and increased medical comorbidities. These findings may inform access to mental health services addressing bereavement and other clinical outcomes after widowhood.

Tumor necrosis factor α (TNFα) regulates inflammation in metabolic diseases and probably aging-associated inflammation. Here, TNFα´s role in aging-related liver inflammation and fibrosis and underlying mechanisms was assessed in mice. In male C57BL/6J mice, aging increased hepatic inflammation, senescence markers p16 and p21 and Tnfa mRNA expression in liver tissue. In a second study, 4 and 24-month-old TNFα^(-/-) and wild-type (WT) mice were compared for senescence, liver damage, intestinal...

Age-related inflammation plays a pivotal role in osteoarthritis (OA) pathogenesis, but the mechanism is not fully understood. Here, we identify decreased IL-36 receptor antagonists (IL-36Ra) in epidermal keratinocytes from a premature-aged skin mice model, aged mice and patients. Decreased IL-36Ra leads to increased secretion of IL-36 agonists to serum and joints, which activates proinflammatory signaling and promotes senescence in chondrocytes and synovial fibroblasts, thereby aggravates OA...

CONCLUSION: These findings emphasize the significant geographic disparity in SO prevalence across China and reveal that SO is associated with a substantially elevated risk of dementia, underscoring the need for targeted interventions in aging populations.

Variability ensures that complex biological systems, including the brain, are capable of responding to changing environmental demands. While the importance of neural variability in electrophysiological and hemodynamic aspects of brain activity is beginning to be understood, little is known about how variability in molecular activity influences brain function. Here, we examine how temporal variability in glucodynamics, or time-varying glucose use, is related to cognition in 35 younger and 43...

Age-associated decline in mitochondrial membrane potential (MMP) is a ubiquitous aspect of eukaryotic organisms and is associated with many aging-related diseases. However, it is not clear whether this decline is a cause or consequence of aging, and therefore whether interventions to reduce MMP decline are a viable strategy to promote healthier aging and longer lifespans. We developed a screening platform in Saccharomyces cerevisiae to identify mutations that slowed or abrogated the...

Aging is a multifactorial process influenced by genetic, environmental, and metabolic factors. Dysregulated nutrient sensing and metabolic dysfunction are hallmarks of aging, and reduction of insulin/IGF-1 signaling or metabolic interventions such as caloric restriction extend lifespan across species. Endogenous metabolites reflect and mediate these metabolic cues, linking nutrient status to epigenetic and transcriptional programs by serving as cofactors for chromatin-modifying enzymes or as...

CONCLUSIONS: This study demonstrates a J-shaped association between DII and PN, which is partially accounted for by biological aging. These findings provide a new perspective for preventing PN through a low-inflammation diet.

Bone aging compromises skeletal integrity and increases vulnerability to osteoporosis and other age-related disorders, underscoring the need for new therapeutic strategies. Although pharmacological and genetic approaches have been widely explored, how cellular mechanical remodeling contributes to bone aging remains unclear. Here, we find that senescent bone marrow stem cells show markedly reduced intracellular force and impaired mechanical behavior. Moderate mechanical stimulation in cell...

Pharmacological modulation of monoaminergic signaling, a process targeted by many therapeutic and recreational drugs via receptors, transporters, degradation enzymes, or reuptake mechanisms, is emerging as a promising aging intervention and as a strategy to treat various maladies. Monoamines (including dopamine, serotonin, and norepinephrine) are central to the regulation of mood, movement, sleep, memory, and systemic physiology. Here, we demonstrate that Reserpine, chronic inhibitor of the...

Frailty is a common geriatric syndrome associated with increased mortality, yet its underlying biological mechanisms and potential value for early risk stratification remain inadequately understood. In this large prospective cohort of more than 260,000 UK Biobank participants with plasma metabolomic profiling, we identified and validated metabolomic signatures of physical frailty and a 49-item frailty index using 50-times repeated 10-fold cross-validated elastic-net regression. The signatures...

FOXOs constitute a class of evolutionarily conserved transcription factors that play pivotal roles in diverse cellular processes, including glucose and lipid metabolism, energy homeostasis, oxidative stress response, and autophagy. They are recognized as central regulators of longevity. This review details the mechanisms linking FOXO to aging. FOXO activity is regulated via nucleocytoplasmic shuttling, a process controlled by phosphorylation and dephosphorylation through the insulin/insulin-like...

Non-cognitive, neuropsychiatric symptoms (NPS) are nearly universal in Alzheimer's disease (AD), but investigation of their underlying biology is complicated by comparative medicine approaches that incompletely capture spontaneous disease, primarily using transgenic rodent models. The aged companion dog, which spontaneously develops an AD-like disease called canine cognitive dysfunction (CCD), may help fill this translational gap. Using data from the Dog Aging Project with > 10,000 aged dogs (>...

Advanced age, comorbidities, and immunocompromised states remain major risk factors for severe or persistent COVID-19 despite vaccination and antivirals, underscoring the need for innovative treatments such as adoptive T-cell therapy (ATT). In this prospective single-center study, we evaluated the safety, feasibility, and efficacy of two ATT approaches in immunocompromised patients with high-risk or persistent SARS-CoV-2 infection: interferon-γ cytokine capture system virus-specific T cells...

Senescence is a driver of aging and a barrier to tumor progression, but its persistent accumulation drives inflammation and relapse. Thus, the success of chemotherapy could be jeopardized when senescence emerges in the tumor microenvironment. Here we identified the senolytic properties of a pore-forming toxin, sticholysin I (StnI). StnI and our engineered improved form, StnIG, selectively hampers viability of chemotherapy-induced senescent cancer cells, as well as senescent primary cells. We...