Single-gene mutations can produce human progeroid syndromes--phenotypes that mimic usual or "normative" aging. These can be divided into two classes--those that have their impacts upon multiple organs and tissues (segmental progeroid syndromes) and those that have their major impacts upon a single organ or tissue (unimodal progeroid syndromes). The prototypic example of the former is the Werner...

Progeroid laminopathies are accelerated aging syndromes caused by defects in nuclear envelope proteins. Accordingly, mutations in the LMNA gene and functionally related genes have been described to cause HGPS (Hutchinson-Gilford progeria syndrome), MAD (mandibuloacral dysplasia) or RD (restrictive dermopathy). Functional studies with animal and cellular models of these syndromes have facilitate...

Susceptibility to senescence caused by defective DNA repair is a major hallmark of progeroid syndrome patients, but molecular mechanisms of how defective DNA repair predisposes to senescence are largely unknown. We demonstrate here that suppression of DNA repair pathways extends the duration of Chk1-dependent G2 checkpoint activation and sensitizes cells to senescence through enhancement of mit...

Zmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation of lamin A, an essential component of the nuclear envelope. Zmpste24-deficient mice exhibit multiple defects that phenocopy human accelerated aging processes such as Hutchinson-Gilford progeria syndrome. In this work, we report that progeroid Zmpste24(-/-) mice present profound transcriptional alterations in genes t...

Hutchinson-Gilford progeria syndrome (HGPS) and Werner's syndrome are representative types of progeroid syndrome. LMNA (Lamin A/C) gene mutation with atypical Werner's syndrome have recently been reported. Atypical Werner's syndrome with the severe metabolic complications, the extent of the lipodystrophy is associated with A133L mutation in the LMNA gene and these patients present with phenotyp...

This question is known as the generalized Busemann-Petty problem. For i = n − 1, the problem was posed by Busemann and Petty [2] in 1956. It has a long history, and the answer is affirmative if and only if n ≤ 4; see [3], [8], [11]. For the generalized Busemann-Petty problem the following statements are known. If i = 2, n = 4, an affirmative answer follows from that in the case i = n − 1. If 3 ...

The likely pathogenic variant c.407A>T p.Asp136Val of the LMNA gene has been recently described in a young woman presenting with atypical progeroid syndrome, associated severe aortic valve stenosis. We further describe cardiovascular involvement syndrome her family. identified seven members general presentation suggestive syndrome. All them presented heart conduction abnormalities: degenerat...