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A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.
Cancers (Basel)
January 2025
Department of Molecular Biosciences, University of South Florida, 4202 East Fowler Avenue, ISA2015, Tampa, FL 33620, USA.
Background/objectives: As cells divide, telomeres shorten through a phenomenon known as telomere attrition, which leads to unavoidable senescence of cells. Unprotected DNA exponentially increases the odds of mutations, which can evolve into premature aging disorders and tumorigenesis. There has been growing academic and clinical interest in exploring this duality and developing optimal therapeutic strategies to combat telomere attrition in aging and cellular immortality in cancer.
View Article and Find Full Text PDFThe anti-senescence effect of D-β-hydroxybutyrate in Hutchinson-Gilford progeria syndrome involves progerin clearance by the activation of the AMPK-mTOR-autophagy pathway.
Geroscience
January 2025
Department of Neuropathology, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), 04510, Mexico City, Mexico.
D-β-hydroxybutyrate, BHB, has been previously proposed as an anti-senescent agent in vitro and in vivo in several tissues including vascular smooth muscle. Moreover, BHB derivatives as ketone esters alleviate heart failure. Here, we provide evidence of the potential therapeutic effect of BHB on Hutchinson-Gilford progeria syndrome (HGPS), a rare condition characterized by premature aging and heart failure, caused by the presence of progerin, the aberrant protein derived from LMNA/C gene c.
View Article and Find Full Text PDFLongitudinal Changes in Myocardial Deformation in Hutchinson-Gilford Progeria Syndrome.
Circ Cardiovasc Imaging
January 2025
Department of Cardiology, Boston Children's Hospital, Boston, MA, USA (F.J.O., F.I.L., A.M.F., D.M.H., A.P.).
The role of the LINC complex in ageing and microgravity.
Mech Ageing Dev
January 2025
Department Oral & Maxillofacial Surgery/Pathology, Amsterdam Movement Sciences & Amsterdam Bone Center (ABC), Amsterdam University Medical Center location Vrije Universiteit Amsterdam & Academic Center for Dentistry Amsterdam (ACTA), Gustav Mahlerlaan 3004, Amsterdam 1081 LA, the Netherlands; TEC-MMG-LIS Lab, European Space Agency (ESA), European Space Research and Technology Center (ESTEC), Keplerlaan 1, Noordwijk 2201 AZ, the Netherlands.
The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex plays a crucial role in connecting the nuclear envelope to the cytoskeleton, providing structural support to the nucleus and facilitating mechanical signaling between the extracellular environment and the nucleus. Research in mechanobiology onboard the International Space Station (ISS) and in simulated microgravity (SMG) highlight the importance of gravity in functional mechanotransduction. Although the altered gravity research regarding mechanobiology has been greatly focused on the cytoskeleton and the extracellular matrix (ECM), recent research demonstrates that SMG also induces changes in nuclear mechanics and gene expression patterns, which have been shown to be LINC complex dependent.
View Article and Find Full Text PDFAngiopoietin-2: A Therapeutic Target for Vascular Protection in Hutchinson-Gilford Progeria Syndrome.
Int J Mol Sci
December 2024
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Hutchinson-Gilford progeria syndrome (HGPS) is a pediatric condition characterized by clinical features that resemble accelerated aging. The abnormal accumulation of a toxic form of the lamin A protein known as progerin disrupts cellular functions, leading to various complications, including growth retardation, loss of subcutaneous fat, abnormal skin, alopecia, osteoporosis, and progressive joint contractures. Death primarily occurs as the result of complications from progressive atherosclerosis, especially from cardiac disease, such as myocardial infarction or heart failure, or cerebrovascular disease like stroke.
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