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Nucleus (Austin, Tex.) 2011Hutchinson-Gilford Progeria Syndrome (HGPS) is a severe premature aging syndrome that affects children. These children display characteristics associated with normal... (Review)
Review
Hutchinson-Gilford Progeria Syndrome (HGPS) is a severe premature aging syndrome that affects children. These children display characteristics associated with normal aging and die young usually from cardiovascular problems or stroke. Classical HGPS is caused by mutations in the gene encoding the nuclear structural protein lamin A. This mutation leads to a novel version of lamin A that retains a farnesyl group from its processing. This protein is called Progerin and is toxic to cellular function. Pre-lamin A is an immature version of lamin A and also has a farnesylation modification, which is cleaved in the maturation process to create lamin A.
Topics: Biomedical Research; England; Humans; Lamin Type A; Mutation; Nuclear Proteins; Progeria; Protein Precursors; Universities
PubMed: 22064469
DOI: 10.4161/nucl.2.6.17605 -
Current Gene Therapy 2021Lamin A/C encoded by the LMNA gene is an essential component for maintaining the nuclear structure. Mutation in the lamin A/C leads to a group of inherited disorders is... (Review)
Review
Lamin A/C encoded by the LMNA gene is an essential component for maintaining the nuclear structure. Mutation in the lamin A/C leads to a group of inherited disorders is known as laminopathies. In the human body, there are several mutations in the LMNA gene that have been identified. It can affect diverse organs or tissues or can be systemic, causing different diseases. In this review, we mainly focused on one of the most severe laminopathies, Hutchinson-Gilford progeria syndrome (HGPS). HGPS is an immensely uncommon, deadly, metameric ill-timed laminopathies caused by the abnormal splicing of the LMNA gene and production of an aberrant protein known as progerin. Here, we also presented the currently available data on the molecular mechanism, pathophysiology, available treatment, and future approaches to this deadly disease. Due to the production of progerin, an abnormal protein leads to an abnormality in nuclear structure, defects in DNA repair, shortening of telomere, and impairment in gene regulation which ultimately results in aging in the early stage of life. Now some treatment options are available for this disease, but a proper understanding of the molecular mechanism of this disease will help to develop a more appropriate treatment which makes it an emerging area of research.
Topics: Cell Nucleus; DNA Repair; Gene Expression Regulation; Gene Silencing; Humans; Lamin Type A; Mutation; Phenotype; Progeria; Telomere
PubMed: 33655857
DOI: 10.2174/1566523221666210303100805 -
The American Journal of Clinical... Jun 1992Progeria is a rare genetic disease with striking features that resemble accelerated aging. The inheritance pattern, paternal age effect, and lack of consanguinity argue... (Review)
Review
Progeria is a rare genetic disease with striking features that resemble accelerated aging. The inheritance pattern, paternal age effect, and lack of consanguinity argue that it is due to a sporadic dominant mutation. We have observed elevated levels of hyaluronic acid (HA) excretion in progeria patients. In several progeria patients we observed normal levels of growth hormone (GH) but very low levels of insulin-like growth factor I along with very high basal metabolic rates (BMRs). A trial of GH treatment was begun, which resulted in a marked increase in linear growth and a paradoxical drop in BMRs in these two patients. We hypothesize that the failure of patients with progeria to thrive may be due to a bioinactive form of GH and a lack of vasculogenesis caused by excess HA. An understanding of the progeria genetic mutation may define a key gene with a major effect on normal aging.
Topics: Basal Metabolism; Growth Hormone; Humans; Hyaluronic Acid; Insulin-Like Growth Factor I; Mutation; Progeria; Werner Syndrome
PubMed: 1590260
DOI: 10.1093/ajcn/55.6.1222S -
Aging Jun 2021
Topics: Extracellular Vesicles; Gastrointestinal Microbiome; Gene Editing; Humans; Molecular Targeted Therapy; Point Mutation; Progeria
PubMed: 34176790
DOI: 10.18632/aging.203254 -
The New England Journal of Medicine Apr 2021
Topics: Animals; DNA; Disease Models, Animal; Gene Editing; Humans; Lamin Type A; Longevity; Mice; Mice, Transgenic; Point Mutation; Progeria
PubMed: 33826825
DOI: 10.1056/NEJMcibr2100661 -
Nature Reviews. Drug Discovery May 2021
Topics: Biological Therapy; Humans; Oligonucleotides, Antisense; Progeria
PubMed: 33772219
DOI: 10.1038/d41573-021-00056-0 -
Anesthetic considerations in children with Hutchinson-Gilford progeria syndrome: A narrative review.Paediatric Anaesthesia May 2020Hutchinson-Gilford progeria syndrome is a rare disease in childhood that results in premature aging. The presence of multisystem derangements including skin, bone, and... (Review)
Review
BACKGROUND
Hutchinson-Gilford progeria syndrome is a rare disease in childhood that results in premature aging. The presence of multisystem derangements including skin, bone, and joint diseases and possibly a difficult airway makes the anesthetic management challenging. Because of the extremely low prevalence, experience is limited even for experienced pediatric anesthesiologists.
OBJECTIVE
To review the available literature on anesthesia for patients with Hutchinson-Gilford progeria syndrome and to give recommendations for establishing the best practice for patients with Hutchinson-Gilford progeria syndrome.
DESIGN
A narrative review of the rare existing literature.
DATE SOURCES
CENTRAL (Cochrane), EMBASE, Google Scholar, MEDLINE and PubMed.
ELIGIBILITY CRITERIA
Articles addressing anesthesia in patients with Hutchinson-Gilford progeria syndrome were included.
RESULTS
An overview of the current literature was made on anesthesia care for patients with Hutchinson-Gilford progeria syndrome. After screening the literature, only ten articles were found to be of interest and include some case reports and a correspondence. The focus points on how to perform anesthesia care in patients with Hutchinson-Gilford progeria syndrome and the entire perioperative care are suggested. The available data are limited and results need to be interpreted with caution.
CONCLUSION
The patients with Hutchinson-Gilford progeria syndrome are not just "frail" patients. Awareness concerning intubation difficulties is mandatory, and airway strategies must be addressed in advance. Although these patients present with the physiology of an elderly with accompanying comorbidities, emotionally they are only children and should be approached as such.
Topics: Adolescent; Anesthesia; Child; Child, Preschool; Female; Humans; Intubation, Intratracheal; Male; Progeria
PubMed: 32128928
DOI: 10.1111/pan.13847 -
Biogerontology Feb 2016Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a de novo genetic mutation that leads to the accumulation of a splicing isoform of... (Review)
Review
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a de novo genetic mutation that leads to the accumulation of a splicing isoform of lamin A termed progerin. Progerin expression alters the organization of the nuclear lamina and chromatin. The life expectancy of HGPS patients is severely reduced due to critical cardiovascular defects. Progerin also accumulates in an age-dependent manner in the vascular cells of adults that do not carry genetic mutations associated with HGPS. The molecular mechanisms that lead to vascular dysfunction in HGPS may therefore also play a role in vascular aging. The vascular phenotypic and molecular changes observed in HGPS are strikingly similar to those seen with age, including increased senescence, altered mechanotransduction and stem cell exhaustion. This article discusses the similarities and differences between age-dependent and HGPS-related vascular aging to highlight the relevance of HGPS as a model for vascular aging. Induced pluripotent stem cells derived from HGPS patients are suggested as an attractive model to study vascular aging in order to develop novel approaches to treat cardiovascular disease.
Topics: Aging; Animals; Blood Vessels; Disease Models, Animal; Humans; Induced Pluripotent Stem Cells; Progeria
PubMed: 26330290
DOI: 10.1007/s10522-015-9602-z -
Current Opinion in Cell Biology Dec 2012The aging rate of an organism depends on the ratio of tissue degeneration to tissue repair. As a consequence, molecular alterations that tip this balance toward... (Review)
Review
The aging rate of an organism depends on the ratio of tissue degeneration to tissue repair. As a consequence, molecular alterations that tip this balance toward degeneration cause accelerated aging. Conversely, interventions can be pursued to reduce tissue degeneration or to increase tissue repair with the aim of delaying the onset of age-associated manifestations. Recent studies on the biology of stem cells in aging have revealed the influence of systemic factors on their functionality and demonstrated the feasibility of reprogramming aged and progeroid cells. These results illustrate the reversibility of some aspects of the aging process and encourage the search for new anti-aging and anti-progeria interventions.
Topics: Aging; Animals; Cellular Reprogramming; Cellular Senescence; Epigenesis, Genetic; Humans; Longevity; Progeria; Rejuvenation; Stem Cells
PubMed: 22959961
DOI: 10.1016/j.ceb.2012.08.009 -
Aging Feb 2024Progeroid disorders are a heterogenous group of rare and complex hereditary syndromes presenting with pleiotropic phenotypes associated with normal aging. Due to the...
Progeroid disorders are a heterogenous group of rare and complex hereditary syndromes presenting with pleiotropic phenotypes associated with normal aging. Due to the large variation in clinical presentation the diseases pose a diagnostic challenge for clinicians which consequently restricts medical research. To accommodate the challenge, we compiled a list of known progeroid syndromes and calculated the mean prevalence of their associated phenotypes, defining what we term the 'progeria phenome'. The data were used to train a support vector machine that is available at https://www.mitodb.com and able to classify progerias based on phenotypes. Furthermore, this allowed us to investigate the correlation of progeroid syndromes and syndromes with various pathogenesis using hierarchical clustering algorithms and disease networks. We detected that ataxia-telangiectasia like disorder 2, spastic paraplegia 49 and Meier-Gorlin syndrome display strong association to progeroid syndromes, thereby implying that the syndromes are previously unrecognized progerias. In conclusion, our study has provided tools to evaluate the likelihood of a syndrome or patient being progeroid. This is a considerable step forward in our understanding of what constitutes a premature aging disorder and how to diagnose them.
Topics: Humans; Progeria; Aging, Premature; Aging; Phenotype; Growth Disorders; Cockayne Syndrome
PubMed: 38345566
DOI: 10.18632/aging.205537