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Selective endoplasmic reticulum (ER) macroautophagy/autophagy, also called reticulophagy, is a disposal pathway that degrades ER domains. A major role of reticulophagy is the removal of ER domains that contain misfolded proteins resistant to ER-associated degradation (ERAD). Our studies have shown that RTN3L, the SEC24C-SEC23 COPII coat subcomplex, and the CUL3^(KLHL12) E3 ligase that ubiquitinates RTN3L targets ERAD-resistant misfolded protein condensates for degradation at ER-reticulophagy...

The silkworm Bombyx mori is an economically important insect for silk production. Its silk glands are responsible for the synthesis and secretion of silk proteins. The naked pupa (Nd), a fibroin heavy chain mutant strain of silkworm, was found to exhibit severe atrophy, degeneration of the posterior silk gland (PSG), and abnormal secretion of fibroin proteins, thereby producing little or no silk. Here, we found that the autophagic marker Atg8-PE was upregulated through the target of rapamycin...

A major challenge in aging research is identifying interventions that can improve lifespan and health and minimize toxicity. Clinical studies cannot consider decades-long follow-up periods, and therefore, in-silico evaluations using omics-based surrogate biomarkers are emerging as key tools. However, many current approaches train predictive models on observational data, rather than on intervention data, which can lead to biased conclusions. Yet, the first classifiers for lifespan extension by...

Telomeres, the protective ends of chromosome, are key to tissue repair and regeneration. Telomere shortening is linked to aging and age-related disorders, while excessive telomerase activity may support tissue regeneration or transformation. Some of the functions of telomeres and telomerase may be mediated by its important role in the process of stemness. Active telomerase, and subsequent telomerase-dependent telomere extension, supports stem-cells self-renewal and pluripotency - essential for...

CONCLUSIONS: Loneliness among both older men and women has decreased over the past three decades. Several factors were found to be associated with loneliness. Given the detrimental impact of loneliness on health of individuals, policies and health strategies aimed at alleviating loneliness among older people should be a top priority.

Ideal silicon negative electrodes for high-energy lithium-ion batteries are expected to feature high capacity, minimal expansion, long lifespan, and fast charging. Yet, engineered silicon materials face a fundamental paradox associated with particle deformation and charge transfer, which hinders the industrial use of advanced silicon electrode materials. Here we show a sieving-pore design for carbon supports that overcomes these mechano-kinetic limitations to enable stable, fast (de)alloying...

CONCLUSION: Important variability in performance, particularly in vulnerable groups, highlights the limitations of a one-size-fits-all and underscores the need for more granular predictive models that account for subpopulation-specific characteristics to enhance mortality risk prediction.

CONCLUSIONS: PA and adherence to the MD are independently associated with sarcopenia. Moreover, specific associations were observed between sarcopenia domains. Nevertheless, no significant interaction was observed between them.

CONCLUSION: In East Asian populations, CHB will increase the incidence of OP. Therefore, CHB patients not only require long-term antiviral treatment to protect the liver but should also monitor their bone health over time to reduce the risk of OP, ultimately improving quality of life.

CONCLUSIONS AND IMPLICATIONS: In conclusion, this review emphasizes the uncertainty surrounding the effectiveness of SB reduction interventions in LTCFs. Future research should refine methodologies, standardize interventions and outcome measures, and build a stronger evidence base to guide intervention development and improve well-being in LTCF residents. Findings also suggest that SB-focused strategies may be more effective than PA-based ones alone and could inform policy and practice...

Cellular senescence is a complex biological process with a dual role in tissue homeostasis and aging-related pathologies. Accumulation of senescent cells promotes chronic inflammation, tissue dysfunction, age-related diseases, and tumor suppression. Recent advancements in immunotherapy have positioned T cell-based approaches as precision tools for the targeted clearance of senescent cells, offering a novel avenue for anti-aging interventions. This review explores the molecular mechanisms...

Acetylcholine (ACh) secreted by the non-neuronal cholinergic system (NNCS), an intrinsic system found in the mammalian heart, is not dependent on neuronal inputs for its synthesis. Accumulating evidence demonstrates that ACh exerts multifaceted cardioprotective effects through the NNCS. Under extreme stress or demand, ACh slows heart rate by modulating cardiac chronotropy. Simultaneously, it protects the myocardium from ischemic, hypoxic, and other stressors. Beyond its direct effects on the...

With age, bones mechanosensitivity is reduced, which limits their ability to adapt to loading. The exact mechanism leading to this loss of mechanosensitvity is still unclear, making developing effective treatment challenging. Current treatments mostly focus on preventing bone mass loss (such as bisphosphonates) or promoting bone formation (such as Sclerostin inhibitors) to limit the decline of bones mass. However, treatments do not target the cause of bone mass loss which may be, in part, due to...

Reactive gliosis is a hallmark of neuropathology and offers a potential target for addressing numerous neurological diseases. Here, we show that growth arrest and DNA damage inducible gamma (GADD45G), a stress sensor in astrocytes, is a nodal orchestrator of reactive gliosis and neurodegeneration. GADD45G expression in astrocytes is sufficient to incite astrogliosis, microgliosis, synapse loss, compromised animal behavior, and the aggravation of Alzheimer's disease (AD). Conversely, silencing...

CONCLUSIONS: Our results suggest that combining motor training with tDCS improves motor function, particularly in gait-related parameters, in PD patients. However, these effects were not sustained over time, highlighting the temporary nature of the benefits. Sex differences may influence the acute effects of combined motor training and tDCS interventions.