New vascular insights into premature aging

Lowenstein, Charles J.; Bennett, John A.

doi:10.1172/jci125616

Cited by 3 publications

(4 citation statements)

References 17 publications

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“…Increases in the ratio of collagen and elastin in aged fibroblasts increase pulmonary stiffness and lower compliance [ 83 ]. The response to shear stress is also altered during aging [ 84 ]. In fact, premature aged ECs from Hutchinson-Gilford progeria syndrome patients impair normal mechanosensing, leading to accelerated fibrosis [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

“…The response to shear stress is also altered during aging [ 84 ]. In fact, premature aged ECs from Hutchinson-Gilford progeria syndrome patients impair normal mechanosensing, leading to accelerated fibrosis [ 84 ]. We have reported that age-related lung diseases, such as pulmonary fibrosis and accompanied pulmonary hypertension, in which changes in mechanical environment are involved in the disease progression [ 85 – 87 ], are prevented in Twist1 fl/fl /Tie2 - cre mice [ 18 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

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Twist1 signaling in age-dependent decline in angiogenesis and lung regeneration

Hendee

Hunyenyiwa

Matus

et al. 2021

Aging

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Angiogenesis – the formation of new blood capillaries- is impaired in aging animals and contributes to the pathogenesis of age-related diseases. A transcription factor, Twist1, contributes to the pathogenesis of age- and angiogenesis-related diseases such as pulmonary fibrosis and atherosclerosis. However, the mechanism by which Twist1 controls age-dependent decline in angiogenesis remains unclear. In this report, we have demonstrated that the levels of Twist1 are higher, while the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) that stimulates angiogenesis, is lower in endothelial cells (ECs) isolated from aged human adipose tissues and mouse lungs compared to those from young tissues. Knockdown of Twist1 in aged human ECs increases the levels of PGC1α and angiogenic factor receptor, vascular endothelial growth factor receptor (VEGFR2), and restores EC proliferation and migration, while inhibition of PGC1α suppresses these effects. Knockdown of Twist1 in supplemented aged ECs also restores vascular networks in the subcutaneously implanted gel, while these effects are abrogated by knockdown of PGC1α. Age-dependent inhibition of post-pneumonectomy (PNX) lung growth is suppressed in Tie2-specific Twist1 conditional knockout mouse lungs, in which VEGFR2 expression increases after PNX. These results suggest that upregulation of endothelial Twist1 mediates age-dependent decline in angiogenesis and regenerative lung growth.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Twist1 signaling in age-dependent decline in angiogenesis and lung regeneration

Hendee

Hunyenyiwa

Matus

et al. 2021

Aging

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“…In addition, Prosser et al recently showed that acute desmin downregulation with a shRNA in rats induces a collapse of the nuclear envelop in a way that is highly reminiscent of Hutchinson-Gilford disease (or Progeria) [48]. Progeria is an extremely rare and complex syndrome characterized by accelerated aging and cardiovascular disease due to mutations in lamins (LMNA) [49]. Therefore, the limited amount of studies addressing the relationship between desmin IF and the nucleus have already highlighted dramatic phenotypes that underscore the relevance of this interaction.…”

Section: Desmin Filaments Are Important For Muscle Structural Integritymentioning

confidence: 99%

New roles for desmin in the maintenance of muscle homeostasis

2021

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Desmin is the primary intermediate filament (IF) of cardiac, skeletal, and smooth muscle. By linking the contractile myofibrils to the sarcolemma and cellular organelles, desmin IF contributes to muscle structural and cellular integrity, force transmission, and mitochondrial homeostasis. Mutations in desmin cause myofibril misalignment, mitochondrial dysfunction, and impaired mechanical integrity leading to cardiac and skeletal myopathies in humans, often characterized by the accumulation of protein aggregates. Recent evidence indicates that desmin filaments also regulate proteostasis and cell size. In skeletal muscle, changes in desmin filament dynamics can facilitate catabolic events as an adaptive response to a changing environment. In addition, post-translational modifications of desmin and its misfolding in the heart have emerged as key determinants of homeostasis and disease. In this review, we provide an overview of the structural and cellular roles of desmin and propose new models for its novel functions in preserving the homeostasis of striated muscles.

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“…HGPS is a systemic disorder that affects the majority of the organs of the body including the skin, bone, skeletal muscle, adipose tissues, heart, and large and small arteries; however, certain tissues and organs like bones, joints, and the blood vascular system are more prominently affected (Gordon et al 2003(Gordon et al , 2014Hamczyk and Andrés 2018;Lowenstein and Bennett 2019;Vidak and Foisner 2016). The children affected with HGPS start exhibiting the symptoms of the disease at the age of 1-2.…”

Section: Clinical Manifestation Of Hgpsmentioning

confidence: 99%

Pharmacotherapy to gene editing: potential therapeutic approaches for Hutchinson–Gilford progeria syndrome

Saxena

Kumar

2020

GeroScience

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Hutchinson-Gilford progeria syndrome (HGPS), commonly called progeria, is an extremely rare disorder that affects only one child per four million births. It is characterized by accelerated aging in affected individuals leading to premature death at an average age of 14.5 years due to cardiovascular complications. The main cause of HGPS is a sporadic autosomal dominant point mutation in LMNA gene resulting in differently spliced lamin A protein known as progerin. Accumulation of progerin under nuclear lamina and activation of its downstream effectors cause perturbation in cellular morphology and physiology which leads to a systemic disorder that mainly impairs the cardiovascular system, bones, skin, and overall growth. Till now, no cure has been found for this catastrophic disorder; however, several therapeutic strategies are under development. The current review focuses on the overall progress in the field of therapeutic approaches for the management/cure of HGPS. We have also discussed the new disease models that have been developed for the study of this rare disorder. Moreover, we have highlighted the therapeutic application of extracellular vesicles derived from stem cells against aging and aging-related disorders and, therefore, suggest the same for the treatment of HGPS.

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New vascular insights into premature aging

Cited by 3 publications

References 17 publications

Twist1 signaling in age-dependent decline in angiogenesis and lung regeneration

Twist1 signaling in age-dependent decline in angiogenesis and lung regeneration

New roles for desmin in the maintenance of muscle homeostasis

Pharmacotherapy to gene editing: potential therapeutic approaches for Hutchinson–Gilford progeria syndrome

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