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The endoplasmic reticulum (ER) is a central organelle that coordinates protein synthesis and processing, lipid metabolism, Ca²⁺ storage, detoxification, and cellular homeostasis. These processes are rigorously regulated, and when the ER encounters external stimuli, it triggers ER stress, a main mechanism that plays a crucial role in determining cellular fate. In addition to its role in apoptosis, further research has unveiled novel physiological functions of ER stress, encompassing its...

Skin aging is a multifactorial process influenced by intrinsic and extrinsic factors, including cellular senescence, photoaging, glycation, and impaired wound healing, all of which begin at birth. Recent epigenetic research has identified non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as key regulators of gene networks governing skin homeostasis, regeneration, and aging. However, the literature remains fragmented, lacking...

Population aging has become a global challenge, with its molecular mechanisms incompletely understood. The signal transducer and activator of transcription 3 (STAT3), a pleiotropic cytoplasmic transcription factor, is extensively involved in almost all hallmarks of aging, exhibiting paradoxical dual roles in senescence progression. This review summarizes the structure of STAT3 and its key posttranslational modifications (PTMs), including phosphorylation (Y705, S727), acetylation, and...

Lumbar multifidus (MF) muscle plays a key role in spinal stability, yet its adaptations to aging and disuse, which become increasingly prevalent with advancing age, remain unclear. We conducted two studies to investigate age- and inactivity-induced changes in MF size. In Study 1, we assessed 32 young adults (50% females) and 75 older adults (67% females), categorized as non-sarcopenic (NS) or probable sarcopenic (PS) based on EWGSOP2 criteria. In Study 2, we examined early MF responses to 10-day...

Interventional therapy and surgery play important roles in the treatment of various diseases, but they cause varying degrees of vascular injury. Currently, the side effects are often overlooked. Here, we observed abnormal nuclear morphology (nuclear dysmorphism) and vascular aging in injured human and rodent arteries. Platelet-derived microvesicles (PMVs) adhere to injured blood vessels, leading to nuclear dysmorphism and cell senescence in vascular smooth muscle cells (VSMCs). This occurs...

Previous studies from our lab identified functional defects in antigen-specific peripheral T follicular helper cells (pTfh), characterized by low IL-21 and high IL-2 production, contributing to non-responsiveness to the influenza vaccine in both aging and HIV. This study investigated how IL-21-induced STAT3 and IL-2-induced STAT5 activation in pTfh cells affects vaccine responses in aging people with HIV (PWH) and those without HIV (PWoH). Ninety participants, including young (Y, ≤ 40 years) and...

Pregnancy functions as a "stress test" with implications for women's long-term health. We hypothesize that maternal biological aging, measured by epigenetic age acceleration (EAA), can be influenced by one-carbon nutritional status (folate, vitamin B₁₂, homocysteine), adherence to the Mediterranean diet, and prenatal multivitamin use. We analyzed data from 742 mothers enrolled in the Boston Birth Cohort (1998-2013). EAA was defined as the difference between the Levine epigenetic clock-DNA...

Psoriasis is a chronic inflammatory skin disease affecting millions of people worldwide. Although growing evidence links chronic inflammation with increased cancer risk, the association between psoriasis and cutaneous squamous cell carcinoma (cSCC) is still elusive. Using cell transplantation and chemical-induced models of cSCC combined with inducible genetically engineered mouse models of psoriasis, we investigated how chronic skin and systemic inflammation affects squamous skin tumor...

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...