Telomeres protect the ends of linear genomes, and the gradual loss of telomeres is associated with cellular ageing. Telomere protection involves the insertion of the 3' overhang facilitated by telomere repeat-binding factor 2 (TRF2) into telomeric DNA, forming t-loops. We present evidence suggesting that t-loops can also form at interstitial telomeric sequences in a TRF2-dependent manner, formi...

Hutchinson-Gilford progeria syndrome (HGPS) is caused by the production of a truncated prelamin A, called progerin, which is farnesylated at its carboxyl terminus. Progerin is targeted to the nuclear envelope and causes misshapen nuclei. Protein farnesyltransferase inhibitors (FTI) mislocalize progerin away from the nuclear envelope and reduce the frequency of misshapen nuclei. To determine whe...

We have recently reported that progeroid Zmpste24-/- mice, which exhibit multiple defects that phenocopy Hutchinson-Gilford progeria syndrome, show a profound dysregulation of somatotropic axis, mainly characterized by the occurrence of very high circulating levels of growth hormone (GH) and a drastic reduction in insulin-like growth factor-1 (IGF-1). We have also shown that restoration of the ...

Hutchinson-Gilford progeria syndrome (HGPS) is a lethal premature and accelerated aging disease caused by a de novo point mutation in LMNA encoding A-type lamins. Progerin, a truncated and toxic prelamin A issued from aberrant splicing, accumulates in HGPS cells' nuclei and is a hallmark of the disease. Small amounts of progerin are also produced during normal aging. We show that progerin is se...

يمسج للاتعا نوسينشتاه ايريجورب دروفليج ةمزلاتم دعت يفحق بسانت مدعب فصتي .دللجا ةشاشهل مزلام رطيسم .رويطلا هطقتلا روهظو ،كفلا رغصو ،يننستلا رخأتو ،يهجو ينج يف افون يد ينج ةرفط وه يسيئرلا يثارولا بيعلا نأ امك 16 رمعلا نم غلبي ضيرم ةلاح ريرقتلا اذه فصي .LMNA يذلاو نوسينشتاه ايريجورب دروفليج ضارعأ روهظ عم ماع ضارعأ ترهظ امك .ريبك لكشب تايبدلأا يف ةلالحا فصو تم ةفلتخلما تاصيخشتلا ةشقانم تم امك .ضيرل...

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature-aging syndrome caused by a dominant mutation in the gene encoding lamin A, which leads to an aberrantly spliced and processed protein termed progerin. Previous studies have shown that progerin induces early senescence associated with increased DNA-damage signaling and that telomerase extends HGPS cellular lifespan. We demonstrate that t...

Abstract Background Osteoarthritis (OA) is one of the most prevalent joint diseases advanced age and a leading cause disability worldwide. Ageing major risk factor for articular cartilage (AC) degeneration that leads to OA, age-related decline in regenerative capacity accelerates OA progression. Here we demonstrate systemic transplantation unique population adult multipotent muscle-derived stem...

Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating incurable premature aging disease caused by accumulation of progerin, a toxic lamin A mutant protein. HGPS patient-derived cells exhibit nuclear morphological abnormalities, altered signaling pathways, genomic instability, and premature senescence. Here we uncover new molecular mechanisms contributing to cellular decline in progeria. ...

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare premature and accelerated aging disease caused by a de novo point mutation in LMNA encoding A-type lamins. Progerin, a truncated and toxic form of prelamin A, accumulates in HGPS cells nuclei and is a hallmark of the disease. We show that progerin is sequestered, together with other proteins (lamins B1/B2, emerin), into abnormally...