Review
Biochemistry & Molecular Biology
Jon Macicior, Beatriz Marcos-Ramiro, Silvia Ortega-Gutierrez
Summary: Progeria is a rare genetic disorder caused by a point mutation in the lamin A gene, resulting in abnormal accumulation of progerin. Patients typically die prematurely at the average age of 14.5 due to significant alterations in the cardiovascular system, bones, skin, and overall growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Wayne A. Cabral, Chris Stephan, Masahiko Terajima, Abhirami A. Thaivalappil, Owen Blanchard, Urraca L. Tavarez, Narisu Narisu, Tingfen Yan, Stephen M. Wincovitch, Yuki Taga, Mitsuo Yamauchi, Kenneth M. Kozloff, Michael R. Erdos, Francis S. Collins
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a mutation in the LMNA gene, resulting in the production of the toxic progerin protein. This study used a mouse model of HGPS to investigate the mechanisms of bone loss associated with the disease. The findings revealed abnormal bone formation, reduced bone mass, and increased fragility in the HGPS mice. The study also identified abnormal differentiation of osteoblasts and upregulation of adipogenic genes as contributing factors to the bone abnormalities in HGPS.
Article
Cardiac & Cardiovascular Systems
Anahita Mojiri, Brandon K. Walther, Chongming Jiang, Gianfranco Matrone, Rhonda Holgate, Qiu Xu, Elisa Morales, Guangyu Wang, Jianhua Gu, Rongfu Wang, John P. Cooke
Summary: The study on a unique HGPS cell model demonstrated the impact of telomere repair on vascular cell aging, suggesting telomerase mRNA as a potential effective therapeutic approach for HGPS. Research on endothelial cells differentiated from patients with HGPS showed that hTERT treatment improved cellular function, restored endothelial function, and reduced the release of inflammatory markers.
EUROPEAN HEART JOURNAL
(2021)
Article
Cell Biology
Cristina Capanni, Elisa Schena, Maria Letizia Di Giampietro, Alessandra Montecucco, Elisabetta Mattioli, Giovanna Lattanzi
Summary: This study reveals the crucial role of prelamin A in the recruitment of 53BP1 and DNA damage repair during stress response. It modulates the structure and affinity of Lamin A/C complexes, affecting subsequent DNA repair processes and contributing to cellular defense response.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Genetics & Heredity
Liza A. Joudeh, Alannah J. DiCintio, Madeline R. Ries, Andrew S. Gasperson, Kennedy E. Griffin, Victoria P. Robbins, Makenzie Bonner, Sarah Nolan, Emma Black, Alan S. Waldman
Summary: In this study, researchers investigated the impact of progerin, a truncated form of lamin A associated with Hutchinson-Gilford Progeria Syndrome (HGPS), on DNA end-joining. They found that progerin expression correlated with a shift towards imprecise end-joining, suggesting compromised genome stability. The findings suggest that progerin plays a role in accelerated and normal aging by affecting DNA repair.
Review
Genetics & Heredity
Noelle J. Batista, Sanket G. Desai, Alexis M. Perez, Alexa Finkelstein, Rachel Radigan, Manrose Singh, Aaron Landman, Brian Drittel, Daniella Abramov, Mina Ahsan, Samantha Cornwell, Dong Zhang
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a rare, autosomal-dominant, and fatal premature aging syndrome caused by a point mutation in the LMNA gene. The resulting mutant protein, progerin, behaves in a dominant-negative fashion, leading to cellular and molecular changes similar to normal aging cells. However, HGPS manifests in an accelerated manner and primarily affects connective tissues. Epigenetic changes in HGPS have been studied and may play a crucial role in the disease's pathogenesis. Recent treatments for HGPS have shown important effects at a cellular level, improving symptoms and increasing lifespan.
Review
Genetics & Heredity
Md Mominur Rahman, Kazi Sayma Ferdous, Muniruddin Ahmed, Mohammad Touhidul Islam, Md Robin Khan, Asma Perveen, Ghulam Md Ashraf, Md Sahab Uddin
Summary: Lamin A/C encoded by the LMNA gene is crucial for nuclear structure maintenance, with mutations leading to laminopathies such as Hutchinson-Gilford progeria syndrome (HGPS). HGPS, caused by abnormal splicing of the LMNA gene and progerin protein production, results in premature aging and is an area of emerging research for developing effective treatments.
CURRENT GENE THERAPY
(2021)
Article
Cell Biology
Yosra Bejaoui, Aleem Razzaq, Noha A. Yousri, Junko Oshima, Andre Megarbane, Abeer Qannan, Ramya Pottabatula, Tanvir Alam, George M. Martin, Henning F. Horn, Thomas Haaf, Steve Horvath, Nady El Hajj
Summary: In this study, the researchers conducted a genome-wide methylation analysis on blood DNA samples from patients with progeroid laminopathies. They found DNA methylation alterations at specific CpG sites and regions, and identified possible pathways/mechanisms involved in the accelerated aging process of progeroid laminopathies. They also observed significant differences in methylation patterns between different subtypes of progeroid laminopathies.
Article
Biochemistry & Molecular Biology
Madaiah Puttaraju, Michaela Jackson, Stephanie Klein, Asaf Shilo, C. Frank Bennett, Leslie Gordon, Frank Rigo, Tom Misteli
Summary: Research has identified an optimized antisense oligonucleotide that can significantly extend lifespan in a mouse model of HGPS, primarily through non-RNase H-mediated mechanisms. In vivo use of optimized ASOs can markedly reduce progerin mRNA levels, but the extent of protein reduction varies between tissues.
Article
Biochemistry & Molecular Biology
Michael R. Erdos, Wayne A. Cabral, Urraca L. Tavarez, Kan Cao, Jelena Gvozdenovic-Jeremic, Narisu Narisu, Patricia M. Zerfas, Stacy Crumley, Yoseph Boku, Gunnar Hanson, Dan V. Mourich, Ryszard Kole, Michael A. Eckhaus, Leslie B. Gordon, Francis S. Collins
Summary: Using an antisense peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) to block pathogenic splicing of mutant transcripts has shown promising results in reducing progerin levels and extending lifespan in a mouse model of Hutchinson-Gilford progeria syndrome.
Article
Cardiac & Cardiovascular Systems
Alvaro Macias, J. Jaime Diaz-Larrosa, Yaazan Blanco, Victor Fanjul, Cristina Gonzalez-Gomez, Pilar Gonzalo, Maria Jesus Andres-Manzano, Andre Monteiro da Rocha, Daniela Ponce-Balbuena, Andrew Allan, David Filgueiras-Rama, Jose Jalife, Vicente Andres
Summary: This study found that heart tissue from Hutchinson-Gilford progeria syndrome (HGPS) patients has structural and electrophysiological defects, including disruption of the t-tubular system, shortened sarcomeres, bradycardia, and atrio-ventricular conduction abnormalities. Chronic treatment with low-dose paclitaxel partially corrected these abnormalities.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Amanda Sanchez-Lopez, Carla Espinos-Estevez, Cristina Gonzalez-Gomez, Pilar Gonzalo, Maria J. Andres-Manzano, Victor Fanjul, Raquel Riquelme-Borja, Magda R. Hamczyk, Alvaro Macias, Lara Del Campo, Emilio Camafeita, Jesus Vazquez, Anna Barkaway, Loic Rolas, Sussan Nourshargh, Beatriz Dorado, Ignacio Benedicto, Vicente Andres
Summary: The study showed that while targeting progerin in mice with mild symptoms produced more significant benefits, it is never too late to treat Hutchinson-Gilford progeria syndrome (HGPS). Restricting the suppression of progerin and restoration of lamin A to vascular smooth muscle cells and cardiomyocytes can effectively prevent vascular disease and normalize lifespan.
Article
Cell Biology
Junyeop Kim, Yerim Hwang, Sumin Kim, Yujung Chang, Yunkyung Kim, Youngeun Kwon, Jongpil Kim
Summary: Partial cellular reprogramming using Oct4, Sox2, Klf4, and c-Myc can rejuvenate cells and reduce aged-cell phenotypes. In this study, we demonstrated that activating the endogenous Oct4 gene through CRISPR/dCas9 system can ameliorate aging in a mouse model of Hutchinson-Gilford progeria syndrome. The activated Oct4 expression not only induced epigenetic remodeling and suppressed progerin accumulation, but also rescued vascular pathological features and lifespan shortening. These findings suggest that CRISPR/dCas9-mediated Oct4 activation could be a promising strategy for treating geriatric diseases.
Article
Biochemistry & Molecular Biology
Jui-Chung Chiang, Wei-Min Chen, Ciara Newman, Benjamin P. C. Chen, Hsinyu Lee
Summary: The study reveals the crucial role of LPA(3) in regulating mitochondrial homeostasis, suppressing mitochondrial stress, and improving mitochondrial function. LPA(3) is found to be a promising therapeutic target for maintaining cellular youth and preventing mitochondrial oxidative stress.
Article
Biochemistry & Molecular Biology
Mi Ri Suh, Ikhyun Lim, Jongwook Kim, Pil-Sung Yang, Jin Seung Choung, Hye Ryeong Sim, Sung Chan Ha, MinYoung Kim
Summary: This study reports therapeutic effects of cord blood cells in a patient with HGPS, showing improvements in anthropometric measures, joint ROM, amelioration of atherosclerosis, and dyslipidemia induced by anti-inflammatory and anti-atherosclerotic responses. No serious adverse events were observed throughout the study period and one year beyond.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Benjamin A. Hilton, Zhengke Li, Phillip R. Musich, Hui Wang, Brian M. Cartwright, Moises Serrano, Xiao Zhen Zhou, Kun Ping Lu, Yue Zou
Article
Neurosciences
Yan Wang, Phillip R. Musich, Kui Cui, Yue Zou, Meng-Yang Zhu
NEUROTOXICITY RESEARCH
(2015)
Article
Biochemistry & Molecular Biology
Benjamin A. Hilton, Ji Liu, Brian M. Cartwright, Yiyong Liu, Maya Breitman, Youjie Wang, Rowdy Jones, Hui Tang, Antonio Rusinol, Phillip R. Musich, Yue Zou
Article
Cell Biology
Hui Tang, Benjamin Hilton, Phillip R. Musich, Ding Zhi Fang, Yue Zou
Article
Biochemistry & Molecular Biology
Phillip R. Musich, Yue Zou
BIOCHEMICAL SOCIETY TRANSACTIONS
(2011)
Article
Biochemistry & Molecular Biology
Benjamin Hilton, Nick Shkriabai, Phillip R. Musich, Mamuka Kvaratskhelia, Steven Shell, Yue Zou
BIOSCIENCE REPORTS
(2014)
Article
Biochemistry & Molecular Biology
Steven M. Shell, Zhengke Li, Nikolozi Shkriabai, Mamuka Kvaratskhelia, Chris Brosey, Moises A. Serrano, Walter J. Chazin, Phillip R. Musich, Yue Zou
JOURNAL OF BIOLOGICAL CHEMISTRY
(2009)
Article
Medicine, Research & Experimental
Jianqun Kou, Phillip R. Musich, Ben Staal, Liang Kang, Yuan Qin, Zhi Q. Yao, Boheng Zhang, Weizhong Wu, Angela Tam, Alan Huang, Huai-Xiang Hao, George F. Vande Woude, Qian Xie
JOURNAL OF TRANSLATIONAL MEDICINE
(2018)
Article
Neurosciences
Yan Wang, Phillip R. Musich, Moises A. Serrano, Yue Zou, Jia Zhang, Meng-Yang Zhu
NEUROTOXICITY RESEARCH
(2014)
Article
Biochemistry & Molecular Biology
M. A. Serrano, Z. Li, M. Dangeti, P. R. Musich, S. Patrick, M. Roginskaya, B. Cartwright, Y. Zou
Article
Multidisciplinary Sciences
Zhengke Li, Phillip R. Musich, Moises A. Serrano, Zhiping Dong, Yue Zou
Article
Multidisciplinary Sciences
Zhengke Li, Phillip R. Musich, Brian M. Cartwright, Hui Wang, Yue Zou
Article
Multidisciplinary Sciences
Benjamin Hilton, Sathyaraj Gopal, Lifang Xu, Sharmistha Mazumder, Phillip R. Musich, Bongsup P. Cho, Yue Zou
Review
Neurosciences
Yan Wang, Erin Xu, Phillip R. Musich, Fang Lin
CNS NEUROSCIENCE & THERAPEUTICS
(2019)
Letter
Genetics & Heredity
Phillip R. Musich, Zhengke Li, Steven M. Shell, Yue Zou