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Neurodegenerative diseases are marked by progressive neuronal damage and currently lack a cure. Recently, exercise has emerged as a promising non-pharmacological approach to potentially slow disease progression and enhance cognitive function. This narrative review summarizes the effects of various exercise modalities-including aerobic exercise, resistance training, and balance training-on four major neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, and...

Potassium is vital for life, yet how potassium homeostasis is maintained at the tissue or organismal level under dietary scarcity remains poorly understood. Stress-activated signaling pathway p38 MAPK is implicated in immune response and aging, but its specific role in low potassium response is unclear. Here we show that a specific p38 MAPK-ATF-7 pathway orchestrates cross-tissue potassium homeostasis in Caenorhabditis elegans. It drives transcriptional upregulation of a crucial P-type ATPase...

CONCLUSIONS AND IMPLICATIONS: Sarcopenia-particularly impaired physical performance-was associated with incident depression in older adults, with clinically meaningful sex-specific patterns. Incorporating simple physical performance measures into routine geriatric assessments may help identify individuals at high risk of late-life depression.

Ischemic cerebrovascular events are among the leading causes of death and disability worldwide, disproportionately affecting the elderly due to vascular aging, oxidative stress, and chronic inflammation. During cerebral ischemia, oxygen and glucose deprivation trigger a cascade of pathological events, including excitotoxicity, mitochondrial dysfunction, blood-brain barrier disruption, and neuroinflammation. Emerging evidence identifies Klotho as a multifunctional protein with anti-aging,...

Aging disrupts systemic metabolism, but the mechanisms by which gut microbial metabolites drive tissue-specific decline remain unclear. We conducted a multi-organ, multi-omics atlas across the gut, serum, liver, lung, and cortex in young and early-aged mice to address this. We identified a conserved aging signature marked by the microbiota-associated depletion of protective circulating metabolites, such as lysophosphatidylcholines (LPCs), concurrently with the systemic accumulation of...

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Obesity and aging are converging health challenges, contributing to morbidity in older populations. However, the specific contribution of age to susceptibility to obesity is unclear. This study examined the impact of age on susceptibility to diet-induced obesity (DIO) and calorie restriction (CR) in male mice. Young (2-3 months) and old (17-24 months) lean C57BL/6J male mice were fed a standard chow diet (CD) or a high-fat diet (HFD) for 28 days, then underwent 18 days of CR. We monitored body...

Twenty years have passed since the first demonstration of mouse induced pluripotent stem cells (iPSCs). What began as an unexpected observation in Kyoto quickly transformed stem cell biology and regenerative medicine worldwide. Over the past two decades, we have gained profound insights into the molecular mechanisms underlying cellular reprogramming and pluripotency. The technology has continued to evolve-becoming safer, more efficient, and more versatile. Today, iPSCs serve as a foundation for...

Somatic mutations, or genetic changes occurring in cells after conception, are widespread in healthy tissues but are conventionally viewed as signs of pre-cancer or simply a consequence of aging. However, an emerging body of work has shown that somatic mutations can drive or protect against disease, which could inspire novel therapeutic strategies. The unexpected depth of genetic diversity within individuals also provides a massive substrate for discovering mutant genes selected for by disease....

Synaptic dysfunction in Alzheimer's disease (AD) may drive synapse loss and cognitive impairment. Whether AD-related synaptic pathophysiology occurs globally, or in specific synapses, is unclear. We investigate in vivo AD-related synaptic dysfunction during early-stage amyloidosis in App^(NL-G-F) mice. We find reduced presynaptic GABAergic proteins at c-Fos-positive excitatory neurons and increased calcium-mediated activity at excitatory and inhibitory neuronal assemblies. In vivo synaptic...

This study aims to explore the shared transcriptomic features of caloric restriction (CR) and endurance exercise in skeletal muscle among older adults. As age increases, muscle atrophy gradually becomes a common issue of functional decline in the elderly. Utilizing bioinformatics analysis, this research identified 101 overlapping differentially expressed genes (DEGs) involved in both CR and endurance exercise. These genes are primarily enriched in key biological pathways related to longevity,...

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Intervertebral disc degeneration (IVDD) is an age-related degenerative spinal disorder, with age as the primary independent risk factor. To investigate the key pathogenic mechanisms of IVDD, we conducted biochemical analyses on IVD specimens from elderly and young groups. In this study, we found that methylmalonic acid (MMA) levels are significantly elevated within the discs of the elderly group, suggesting that MMA may be a critical metabolite involved in aging-induced IVDD. In in vitro...

Neurodegenerative diseases are strongly associated with aging and oxidative stress, underscoring the need for natural compounds that promote healthy aging. The mycosporine-like amino acid (MAA) "palythine", a photoprotective metabolite, exhibits promising bioactivity in mitigating age-related decline. Ultraviolet-B (UV-B, 280-315 nm) radiation is a major inducer of DNA damage, oxidative stress and apoptosis, all of which accelerate aging. In this study, we investigated the effects of palythine...

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Lecanemab, an anti-amyloid antibody, has demonstrated a significant clinical benefit in slowing cognitive decline in early Alzheimer's disease (AD). A mechanistic Neuro-Dynamic Quantitative Systems Pharmacology (QSP) model was developed to capture the temporal and biological complexity of AD progression. This QSP model incorporates three interlinked modules reflecting core aspects of AD pathology: Aβ accumulation, tau pathology, and cognitive decline, where Aβ accumulation promotes tau...

Aging is a primary risk factor for chronic diseases, with cellular senescence as an effective target to delay, prevent or alleviate age-related disorders. Here we report in vitro screening outputs from a natural medicinal agent library, wherein dihydromyricetin, a natural flavonoid, showed senotherapeutic potential. Dihydromyricetin protects senescent fibroblasts against further DNA damage and attenuates the senescence-associated secretory phenotype, acting as a senomorphic agent. Proteomics...

Aging involves multiple detrimental changes in the systemic milieu, leading to functional deterioration and age-related diseases. However, the potential self-protective adaptive alterations during aging remain underexplored. Here we show that phosphoenolpyruvate (PEP), a glycolytic metabolite, acts as a protective factor against age-related chronic inflammation. Longitudinal analyses in mice and humans reveal a biphasic PEP trajectory, characterized by initial accumulation followed by...

CONCLUSION: The study indicates the causality between hypertension and sarcopenia, potentially mediated by insulin resistance (BMI, insulin, FBG, HbA1c, and TG). It provides crucial evidence for the genetic association between hypertension and sarcopenia, while also offering insights for managing both conditions, particularly in terms of blood glucose, lipid, and weight control.