Aging & Longevity

Normative models are increasingly used to characterize individual-level brain deviations in neuroimaging studies, but their performance depends heavily on the reference sample used for training or adaptation. In this study, we systematically investigated how sample size and covariate composition of the reference cohort influence model fit, deviation estimates, and clinical readouts in Alzheimer's disease (AD). Using a discovery dataset (OASIS-3, n = 1032), we trained models on healthy control...

RNA polymerase I (Pol I) is a specialized eukaryotic enzyme responsible for transcribing ribosomal DNA into precursor rRNA, a process that initiates ribosome biogenesis and supports cellular growth, metabolism, and proliferation. Recent structural and mechanistic studies have revealed unique features of Pol I architecture that enable high transcriptional output and tight regulatory control. Pol I activity is dynamically regulated by signaling pathways, epigenetic mechanisms, and chromatin...

Falls in older adults result from declines in muscle quality. This study aimed to examine differences in load-velocity profile (LVP) metrics, muscle ultrasound measures, strength, functional tests, and lifestyle between older adults with and without falls, and to analyze their association with sit-to-stand power. Sixty-two older adults (41 non-fallers, 21 fallers; mean age 68.32 ± 5.07 years) underwent three lab sessions. LVP was determined via functional electromechanical dynamometry during a...

Sleep disturbances and Alzheimer's disease (AD) are interconnected public health challenges. However, the underlying mechanisms of their complex relationships remain elusive. Here, we propose a hypothetical integrative, stream-like model outlining how external and internal exposome factors accelerate brain aging, thereby exacerbating circadian dysregulation, orexin-mediated hyperexcitability, metabolic imbalance, and inflammaging. These changes can lead to increased sleep fragmentation and...

Sjögren's disease, an autoimmune disorder characterized by the presence of circulating autoantibodies and lymphocytic infiltrates in salivary glands, predominantly affects women later in life. By leveraging genetically heterogeneous UM-HET3 mice, this study tested the hypothesis that female sex and aging interact to shape susceptibility to autoimmunity and salivary gland inflammation. Female and male UM-HET3 mice were evaluated across the adult lifespan for the development of glandular...

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...

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...

Age-related alterations of the haemostatic system substantially contribute to the heightened thrombotic and bleeding risk observed in older adults. While age-associated changes in coagulation have been extensively characterised, impairment of fibrinolysis remains comparatively underexplored, particularly in the context of anticoagulation management. Ageing promotes a hypofibrinolytic milieu through endothelial dysfunction, chronic low-grade inflammation, cellular senescence, and structural...

Solubility regulates protein function, but how it is governed by aging remains elusive. Here, we utilized mass spectrometry to define the relative composition of the soluble and insoluble tissue/organ fractions during mouse aging. In the young, there is a wide (∼100-1,000×) range of insoluble/soluble protein ratios that differ tissue-specifically. With aging, some proteins become relatively more insoluble, while others are conversely regulated or unaffected. Age-related insoluble/soluble changes...