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The potential use of pro-senescence therapies, known as TIS (Therapy-Induced Senescence), for the treatment of colorectal cancer (CRC) generated significant interest since they require lower doses compared to those required for inducing apoptosis. However, the senescent cell cycle-arrested cancer cells are long-lived, and studies have revealed escape mechanisms contributing to tumor recurrence. To deepen our understanding of the survival pathways used by senescent cancer cells, we delved into...

CONCLUSIONS: Cognitive functions explained gait speed and step length during normal walking, as well as the decrease of gait speed while performing a concurrent cognitive task. The results suggest that different cognitive processes are important for different postural control aspects. Postural sway in quiet stance, step time and gait variability seem to depend more on physical and automatic processes rather than higher cognitive functions among physically active older people. The relationships...

CONCLUSIONS: The empirical evidence generated by this study posits that the impact of physical activity on MCI is partially mediated through physical performance in an aging population with T2DM residing in rural environments. Consequently, interventional strategies aimed at ameliorating physical performance may serve as a viable approach to mitigate the progression of cognitive decline.

Bis(monoacylglycero)phosphate (BMP) is an abundant lysosomal phospholipid required for degradation of lipids, particularly gangliosides. Alterations in BMP levels are associated with neurodegenerative diseases. Unlike typical glycerophospholipids, lysosomal BMP has two chiral glycerol carbons in the S (rather than the R) stereo-conformation, protecting it from lysosomal degradation. How this unusual and yet crucial S,S-stereochemistry is achieved is unknown. Here, we report that phospholipases...

Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, has emerged as a key regulator of cellular processes linked to ageing and neurodegeneration. SIRT1 modulates various signalling pathways, including those involved in autophagy, oxidative stress, and mitochondrial function, which are critical in the pathogenesis of neurodegenerative diseases. This review explores the therapeutic potential of SIRT1 in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD),...

Retrotransposable elements (RTEs) are common mobile genetic elements comprising ∼42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. We identify cell type marker RTEs in...

Maintaining mitochondrial homeostasis is crucial for cell survival and organismal health, as evidenced by the links between mitochondrial dysfunction and various diseases, including Alzheimer's disease (AD). Here, we report that lncMtDloop, a non-coding RNA of unknown function encoded within the D-loop region of the mitochondrial genome, maintains mitochondrial RNA levels and function with age. lncMtDloop expression is decreased in the brains of both human AD patients and 3xTg AD mouse models....

Stimulator of interferon genes (STING) is activated in many pathophysiological conditions, leading to TBK1-dependent interferon production in higher organisms. However, primordial functions of STING independent of TBK1 are poorly understood. Here, through proteomics and bioinformatics approaches, we identify lysosomal biogenesis as an unexpected function of STING. Transcription factor EB (TFEB), an evolutionarily conserved regulator of lysosomal biogenesis and host defense, is activated by STING...

In a Science paper, Park et al. identified interleukin (IL)-1α as a key driver of positive feedback in inflammaging, linking aging-associated downregulation of DNMT3A to increased IL-1α production in lung myeloid cells. This triggers emergency myelopoiesis in the bone marrow, amplifying myeloid-mediated intratumoral immunosuppression for tumor progression in aged mice.

Epigenetic clocks provide an accurate molecular readout of epigenetic age and epigenetic age acceleration (EAA) derived from DNA methylation data have shown promise as biomarkers of ageing. This systematic review synthesised research on associations between EAA measures and various physiological, cognitive, social, and environmental factors. A comprehensive search strategy identified 299 publications reporting 1050 unique EAA-factor associations based on 53 methylation clocks. Random-effects...

Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, has emerged as a key regulator of cellular processes linked to ageing and neurodegeneration. SIRT1 modulates various signalling pathways, including those involved in autophagy, oxidative stress, and mitochondrial function, which are critical in the pathogenesis of neurodegenerative diseases. This review explores the therapeutic potential of SIRT1 in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD),...

CONCLUSION: Although n-3 fatty acid intake was associated with grip strength index in older women, regardless of their activity status, the magnitude of this association was very small and unlikely to be clinically relevant. Additionally, n-3 fatty acid was not associated with muscle mass index.

Chen, L., Yang, R., Qiao, W., Zhang, W., Chen, J., Mao, L., Goltzman, D., Miao, D. (2019). 1,25-Dihydroxyvitamin D exerts an antiaging role by activation of Nrf2-antioxidant signaling and inactivation of p16/p53-senescence signaling. Aging Cell, 18(3), e12951. https://doi.org/10.1111/acel.12951 The above article, published online on 24 March 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between; the journal Editor-in-Chief, Monty Montano; The Anatomical...

While previous studies identified common genetic variants associated with longevity in centenarians, the role of the rare loss-of-function (LOF) mutation burden remains largely unexplored. Here, we investigated the burden of rare LOF mutations in Ashkenazi Jewish individuals from the Longevity Genes Project and LonGenity study cohorts using whole-exome sequencing data. We found that centenarians had a significantly lower burden (11-22%) of LOF mutations compared to controls. Similar effects were...

Biological clocks and other molecular biomarkers of aging are difficult to implement widely in a clinical setting. In this study, we used routinely collected hematological markers to develop an aging clock to predict blood age and determine whether the difference between predicted age and chronologic age (aging gap) is associated with advanced aging in mice. Data from 2,562 mice of both sexes and three strains were drawn from two longitudinal studies of aging. Eight hematological variables and...

CONCLUSIONS: This Delphi study reveals significant disparities in social and healthcare policies for older adults across Mediterranean countries, highlighting shared challenges and specific national needs. European nations like Greece and Spain face fragmented systems, while non-European countries such as Lebanon, Egypt, and Tunisia lack specialized geriatric services and social security. All countries urgently need better professional training, social and economic empowerment of older adults,...

CONCLUSION: Three trends were observed at the social engagement level. Older adults with initially high levels of social engagement exhibited a continuous upward trend, whereas those with initially low levels experienced a decline in their social engagement, and those with initially intermediate levels remained quite stable. Considering the primary heterogeneous factors, it is imperative for governments to enhance basic services and prioritize the well-being of older adults. Additionally,...

Stem cell therapies for Parkinson's disease are at an exciting time of development, and several clinical trials have recently been initiated. Human pluripotent stem cells are differentiated into transplantable dopamine (DA) progenitors which are proliferative at the time of grafting and undergo terminal differentiation and maturation in vivo. While the progenitors are homogeneous at the time of transplantation, they give rise to heterogeneous grafts composed not only of therapeutic DA neurons...

Oligodendrocyte precursor cells (OPCs) generate myelinating oligodendrocytes and are the main proliferative cells in the adult central nervous system. OPCs are a heterogeneous population, with proliferation and differentiation capacity varying with brain region and age. We demonstrate that during early postnatal maturation, cortical, but not callosal, OPCs begin to show altered passive bioelectrical properties, particularly increased inward potassium (K^(+)) conductance, which correlates with G1...

The special AT-rich sequence-binding (SATB) protein DVE-1 is widely recognized for its pivotal involvement in orchestrating the retrograde mitochondrial unfolded protein response (mitoUPR) in C. elegans. In our study of downstream factors contributing to lifespan extension in sensory ciliary mutants, we find that DVE-1 is crucial for this longevity effect independent of its canonical mitoUPR function. Additionally, DVE-1 also influences lifespan under conditions of dietary restriction and...