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Mild cognitive impairment (MCI) is the prodromal stage of dementia involving complex interactions between the brain and peripheral organs. Emerging evidence indicates that heart dysfunction and gut microbiota dysbiosis contribute to MCI pathogenesis. Here, we present a framework integrating brain-heart-gut interactions using whole-body positron emission tomography (PET) to enhance brain-only diagnostic performance. Our brain-only model achieves diagnostic performance comparable to that of...

CONCLUSIONS: The anti-ASC N-terminal and C-terminal antibodies may have neuroprotective effects, which are manifested as reducing cell apoptosis, improving cognitive function, and alleviating AD-like pathology in AD mice. Immunotherapies targeting ASC are promising for treating AD.

Mitochondrial dysfunction is increasingly recognized as a central driver of Alzheimer's disease (AD), contributing to neuroinflammation, synaptic failure, and energy collapse.Emerging preclinical evidence suggests that classic hallucinogens, such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), mescaline, may restore mitochondrial integrity by activating Serotonin 2A (5-HT2A) and sigma-1(Sig-1R) receptors. In experimental models, these pathways are associated with...

Formation of new amyloid fibrils and oligomers from monomeric protein on the surfaces of existing fibrils is an important driver of many disorders such as Alzheimer's and Parkinson's diseases. The structural basis of this secondary nucleation process, however, is poorly understood. Here, we ask whether secondary nucleation sites are found predominantly at rare growth defects: irregularities in the fibril core structure incorporated during their original assembly. We first demonstrate using the...

Aging is a major risk factor for diabetic kidney disease (DKD), with both conditions exhibiting similar renal pathology. We identify the energy-sensing molecule Retinoic acid-related orphan receptor γ (RORγ) as significantly downregulated in diabetic and aged kidneys. Tubule-specific RORγ deficiency exacerbates kidney injury, whereas its overexpression protects. Mechanistically, RORγ stabilizes insulin-induced gene 1 (INSIG1) by upregulating the deubiquitinase YOD1 and enhancing AMPK activity...

Skeletal muscle aging causes loss of both muscle mss and strength, often leading to sarcopenia. Clinical manifestation of sarcopenia has been found to improve with exercise intervention. The molecular mechanisms in response to exercise intervention in aged skeletal muscles are not fully understood. We performed transcriptomic profiling of aged animal model with exercise intervention for identifying the plausible mechanism leading to enhanced muscle function. Expression levels of 43,629 RNAs were...

We leveraged allele frequencies from gnomAD, Regeneron Genetics Center Million Exome and Turkish Variome for 4591 disease genes from PanelApp and OMIM, and identified 97,135 pathogenic and 478,263 likely pathogenic variants using an American College of Medical Genetics and Genomics-based classifier. This expanded pathogenic and likely pathogenic variants nearly six-fold. On average, an individual is born with 4.70 pathogenic or likely pathogenic variants, of which 1.66 are compatible with a...

Cellular senescence is an evolutionarily conserved stress response that contributes to tissue repair and tumor suppression, yet its accumulation is also linked to aging and disease. Whether physiological senescence can be exploited by oncogenic events to promote tumorigenesis is unknown. Postpartum mammary gland involution is a major adult tissue remodeling event, resembling wound healing, and is closely associated with postpartum breast cancer. Here, we show that during mammary gland involution...

The global rise in life expectancy underscores the urgent need to extend healthspan and prevent age-related diseases. Cardiovascular disease is the leading cause of death worldwide, with ageing as a major non-modifiable risk factor. Ageing drives progressive vascular dysfunction and cardiac decline, including heart failure with preserved or reduced ejection fraction. Vascular cells are particularly vulnerable to ageing, resulting in structural and functional deterioration of the microvasculature...

Long-term preservation of digital information is vital for safeguarding the knowledge of humanity for future generations. Existing archival storage solutions, such as magnetic tapes and hard disk drives, suffer from limited media lifespans that render them unsuitable for long-term data retention^(1-3). Optical storage approaches, particularly laser writing in robust media such as glass, have emerged as promising alternatives with the potential for increased longevity. Previous work^(4-16) has...

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Redox dysregulation, characterized by an imbalance in the NAD^(+) [nicotinamide adenine dinucleotide (oxidized form)]/NADH (reduced form of NAD^(+)) ratio, is implicated in neurodegenerative and psychiatric disorders such as Alzheimer's disease and schizophrenia. This imbalance contributes to mitochondrial dysregulation, oxidative stress, and inflammation. Despite promising preclinical studies supporting therapeutic strategies aimed at restoring redox balance and thereby rescuing brain...

Amorphous materials driven away from equilibrium display a diverse repertoire of complex, history-dependent behaviors. One striking feature is a failure to return to equilibrium after an abrupt change in otherwise static external conditions. Instead, amorphous materials often exhibit physical aging: an ever-slowing, nonexponential relaxation that can span a huge range of timescales. Here, we examine the aging behavior of three different amorphous materials subjected to slow periodic driving. The...

Negative social ties, or "hasslers," are pervasive yet understudied components of social networks that may accelerate biological aging and morbidity. Using ego-centric network data and DNA methylation-based biological aging clocks (i.e., DunedinPACE and age-accelerated GrimAge2) from saliva from a state representative probability sample in Indiana, we examine how negative social ties are associated with accelerated biological aging and a broad range of health outcomes, including inflammation and...

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Laser-written patterns on glass could store data for millennia at a time

CONCLUSION: These findings support a relationship between declines in uneven terrain mobility and n-back cognitive function in older adults; however, this relationship was not observed in younger adults. Further research is needed to understand the shared neural mechanisms underlying age-related declines in mobility and cognitive function.

Aging is accompanied by progressive deterioration in physiological homeostasis, increasing vulnerability to metabolic, neurodegenerative, cardiovascular, and immune disorders. Over the past two decades, circadian biology has emerged as a central integrative framework linking environmental time cues to cellular, tissue, and organismal resilience. The circadian timing system (CTS), composed of a central pacemaker in the suprachiasmatic nucleus (SCN) and peripheral clocks throughout the body,...