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CONCLUSIONS AND IMPLICATIONS: The high prevalence and cross-country differences highlight the complexity of multimorbidity among adults aged 50 years and older in Europe and Israel. The findings reinforce the influence of demographic, clinical, and lifestyle factors and emphasize the need for public policies promoting healthy aging and integrated health care.

Entropy may play an underappreciated role in human aging, such as in skeletal muscle functional declines. Histologically, muscle appears increasingly disorganized with aging, with greater fiber size variability and fiber-type grouping. We tested the hypothesis that entropy is associated with reduced physical performance and muscle function, independent of muscle mass. We quantified a homeostatic dysregulation index of muscle (HDI(M)) as a proxy for entropy of muscle fiber disorganization based...

Clonal haematopoiesis (CH) is the presence of acquired mutations in blood cells and is a consequence of ageing that is linked to malignancy, cardiovascular disease and other diseases of ageing. CH is a reflection of genomic instability with ageing; however, there is evidence that CH may exacerbate features of normal ageing, including inflammageing and immunosenescence, and more directly contribute to disease causation. CH can manifest as mosaic loss of X or Y, autosomal mosaic chromosomal...

With the introduction of adaptive deep brain stimulation (aDBS) for Parkinson's disease, new questions emerge regarding who, why, and how to treat. This paper outlines the pathophysiological rationale for aDBS, which provides real-time modulation of the stimulation amplitude based on subthalamic beta (range 13-30 Hz) activity and related physiomarkers. We review clinical evidence comparing aDBS with conventional DBS in terms of motor improvement, side-effect reduction, energy efficiency, and...

Ageing is associated with a loss of skeletal muscle mass, strength and function, termed sarcopenia. The presence of sarcopenia is known to be problematic leading to an increased risk of falls, fractures and mortality. Age-related changes in the gut microbiome, characterized by reduced diversity and altered metabolite production, may compromise intestinal barrier function, leading to increased permeability. These age-associated changes in the gut microbiome led to changes in circulating microbial...

Aqueous Zn | |I(2) batteries, involving I^(-)/I⁰/I^(+) redox, are promising yet usually facing low I(2) utilization dominated by I⁰/I^(+) redox, especially under high loadings. Unlocking alternative pathway to I⁰/I^(+) redox, preferably in noncorrosive dilute electrolytes, is a crucial solution. Here, we report a pathway towards more thermodynamically favorable I⁰/I^(+) redox, via a unique carbon-halogen bond substitution. This pathway is realized with a low-concentrated (0.7 M), noncorrosive...

Although aging is a universal event, some individuals are able to achieve extreme longevity. The Long-Life Family Study (LLFS) enrolls participants from families enriched with long-lived individuals, serves as a valuable dataset for studying ageing phenotypes and identify potential intervention targets. We analyzed the association between age at blood draw and 16,284 RNAseq-based blood transcriptomic data from 2,167 LLFS participants with ages ranging from 18 to 107, replicated the results in...

Changes in human survival and mortality patterns resulting in life expectancy (LE) increase are profoundly significant for society and critically depend on societal factors but cannot escape frames defined by biology. Demography, a social discipline, uses descriptive terms, such as survival curve rectangularization, mortality compression, lifespan disparity reduction, and mean (modal, median) lifespan increase, to define the beneficial changes thought possible due to deceleration of aging. The...

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Brain aging is characterized by neuroinflammation and lactate metabolic changes. However, the functional role of FGF21 in the aging brain and its influence on lactate homeostasis remains unclear until now. In the study, male C57BL/6 mice were divided into 2-month-old (control), 20-month (aging), and FGF21-treated aging mice (FGF21). We also examined the MAPK signals and astrocyte-neuron lactate shuttle (ANLS) proteins in wild-type and hydroxycarboxylic acid receptor 1-knockout (HCA1-KO) mice...

Aging is the strongest risk factor for dementia; however, few studies have examined the association of biological aging with incident dementia. We analyzed 6069 cognitively unimpaired women (mean age = 70.0 ± 3.8 years) in the Women's Health Initiative Memory Study to examine the association of accelerated biological aging, measured with second and third-generation epigenetic clocks (AgeAccelPheno and AgeAccelGrim2, and DunedinPACE, respectively) with incident mild cognitive impairment (MCI) and...

Skin aging is driven by both extrinsic factors, such as ultraviolet exposure, and intrinsic, chronological processes that lead to progressive deterioration in skin homeostasis and structure. Chronological aging is associated with replicative senescence and a range of molecular and cellular alterations, including genomic instability, mitochondrial dysfunction, and impaired intercellular communication. The dynamic cross-talk between dermal fibroblasts and epidermal keratinocytes is crucial for...

Cellular senescence is the core cytological basis for organismal aging and the development of age-related diseases. Accumulating evidence indicates that senescent phenotypes can be maintained long-term even after the removal of senescence-inducing stressors, and may even affect daughter cells and offspring. This review systematically proposes an integrated theoretical framework of "aging metabolic memory", explaining the persistence, transmissibility, and potential heritability of aging from a...

Physicists combined human acumen and AI-assisted math to show that a doubted particle interaction is possible after all

Early intervention is the most effective strategy to impede the progression of Alzheimer's disease (AD), depending on the identification of early diagnostic biomarkers. Here, we isolate neuron-derived exosomes (NDEs) from plasma of familial AD (FAD), presymptomatic FAD (pre-FAD), and healthy controls (cognitively normal [CN]), followed by label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A specific peptide from protein phosphatase 2 regulatory subunit B'β (PPP2R5C)...

Dysfunction of transactive response DNA-binding protein 43 (TDP-43) drives neurodegeneration in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), in part through inducing aberrant RNA splicing. However, whether such mis-splicing yields stable, pathogenic proteins remains unclear. Here, we identify a TDP-43-repressed cryptic exon in Protein kinase N1 (PKN1), designated PKN1-5a1, which is activated in ALS patient brains and introduces a premature termination codon. This aberrant...

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including...

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