Speeding up the clock: The past, present and future of progeria

Abstract

Progeria is a devastating disorder in which patients exhibit signs of premature aging. The most well-known progeroid syndromes include Hutchinson-Gilford Progeria Syndrome (HGPS) and Werner Syndrome (WS). While HGPS and WS are rare, they often result in severe age-associated complications starting in the early developmental period or after the pubertal growth spurt during adolescence, respectively. In addition, patients with HGPS ultimately die of diseases normally seen in the elderly population, with stroke and myocardial infarction as the leading causes of death. Many WS patients develop similar cardiovascular complications but also have an increased predisposition to developing multiple rare malignancies. These premature aging disorders, as well as animal and cell culture models that recapitulate these diseases, have provided insight into the genetics and cellular pathways that underlie these human conditions and have also uncovered possible mechanisms behind normal aging. Here we discuss the history, the types of progeria, and the various pathophysiological mechanisms that drive these diseases. We also address recent medical advances and treatment modalities for patients with progeria.

POLD1: Central mediator of DNA replication and repair, and implication in cancer and other pathologies

“…As with MDPL, progeria ( Swahari and Nakamura, 2016 ) is a hallmark of Werner syndrome (WS) (#277700 in OMIM) ( Oshima et al, 2016 ). In classical WS, which affects 1 in 200,000 individuals in the United States and has a significantly higher frequency of cases in Japan, patients have multiple symptoms associated with premature aging, and a propensity to atherosclerosis and some types of cancer ( Oshima et al, 2016 ).…”

Manipulating the mechanics of extracellular matrix to study effects on the nucleus and its structure

“…Indeed, 'laminopathies' resulting from lamin-A mutations (e.g. dilated cardiomyopathies and Hutchinson-Gilford Progeria Syndrome) typically cause defects that are most pronounced in stiff tissues such as muscle or bone (Cho et al, 2018;Swahari and Nakamura, 2016). Furthermore, frequent nuclear membrane rupture is seen in mutant cells or lamin-A depleted cells when cultured on stiff substrate where the tension is high (Tamiello et al, 2013;Xia et al, 2018).…”

Anais Do Ii Cogempi E Ii Colagempi

“…FISIOPATOLOGIA DA HIPERPLASIA ADRENAL CONGÊNITA ¹Camille Cunha de Carvalho, ²Iago Pierot Magalhães, ³Ian Loiola Guimarães Alencar, 4 João Manoel Almeida Santos, 5 Michel Lauzer Borges Barreto, 6 Eliamara Barroso Sabino Nogueira ¹ Acadêmico do Curso de Medicina; Centro Universitário UNINOVAFAPI; ² Acadêmica do Curso de Medicina; Centro Universitário UNINOVAFAPI; ³ Acadêmica do Curso de Medicina; Centro Universitário UNINOVAFAPI; 4 Acadêmico do Curso de Medicina; Centro Universitário UNINOVAFAPI; 5 Acadêmico do Curso de Medicina; Centro Universitário UNINOVAFAPI; 6 Professora Doutora em Biotecnologia UNINOVAFAPI Autor para correspondência: João Manoel Almeida Santos E-mail: joaomanoelalmeidasantos98@gmail.com RESUMO INTRODUÇÃO: Hiperplasia adrenal congênita consiste em um conjunto de síndromes causadas por um erro inato do metabolismo, sendo transmitida como herança autossômica recessiva. Caracteriza-se por defeitos enzimáticos que levam à síntese deficiente do cortisol e excesso de androgênios adrenais.…”