Breaking News
December 17, 2018 - Will saliva translate to a real diagnostic tool?
December 17, 2018 - DFG establishes nine new Research Units and one new Clinical Research Unit
December 17, 2018 - Assisted living’s breakneck growth leaves patient safety behind
December 17, 2018 - America’s teens report dramatic increase in their use of vaping devices in just one year
December 17, 2018 - Enlarged heart linked to a higher risk of dementia
December 17, 2018 - Prostate cancer detection using MRI now first-line investigation tool
December 17, 2018 - Adolescents who use cognitive reappraisal had better metabolic measures, shows study
December 17, 2018 - Probiotics may offer therapeutic benefits for biopolar patients
December 17, 2018 - Stealth BioTherapeutics Granted Fast Track Designation for Elamipretide for the Treatment of Dry Age-Related Macular Degeneration with Geographic Atrophy
December 17, 2018 - Studies reveal role of red meat in gut bacteria, heart disease development
December 17, 2018 - Eisai enters into agreement with Eurofarma for its anti-obesity agent lorcaserin
December 17, 2018 - Researchers use brain connectome to reassess neuroimaging findings of Alzheimer’s disease
December 17, 2018 - “Miracle” baby survives Ebola in Congo and rapid a new Ebola detection device
December 17, 2018 - Mechanisms behind neonatal diabetes uncovered
December 17, 2018 - AHF urges the WHO to expedite approval process for vaccine effective against Ebola
December 17, 2018 - Study finds misuse of benzodiazepines to be highest among young adults
December 17, 2018 - TGen receives PayPal grant to underwrite costs of genetic tests for children with rare disorders
December 17, 2018 - New research highlights why HIV-infected patients suffer higher rates of cancer
December 17, 2018 - Antibiotic-resistant bacteria could soon be targeted with Alzheimer’s drug
December 17, 2018 - Rutgers scientists take an important step in making diseased hearts heal themselves
December 17, 2018 - Tailored Feedback at CRC Screen Improves Lifestyle Behaviors
December 17, 2018 - Loss of two genes drives a deadly form of colorectal cancer, reveals a potential treatment
December 17, 2018 - How the Mediterranean Diet Can Help Women’s Hearts
December 17, 2018 - Sustained connections associated with symptoms of autism
December 17, 2018 - Concussion rates among young football players were higher than previously reported
December 17, 2018 - Cresco Labs granted approval to operate marijuana dispensary in Ohio
December 17, 2018 - Study provides insight into health risks facing new mothers
December 17, 2018 - AMSBIO expands Wnt signaling pathway product range to aid research
December 16, 2018 - Surgical treatment unnecessary for many prostate cancer patients
December 16, 2018 - Excess weight responsible for cancers globally finds report
December 16, 2018 - Regular sex associated with greater enjoyment of life in seniors
December 16, 2018 - Social stigma contributes to poor mental health in the autistic community
December 16, 2018 - Multidisciplinary team successfully performs complex surgery on patient suffering from enlarged skull
December 16, 2018 - Experts analyze data that can guide antidepressant discontinuation
December 16, 2018 - Menlo Therapeutics’ Successful Phase 2 Clinical Trial of Serlopitant Demonstrates Reduction of Pruritus Associated with Psoriasis
December 16, 2018 - Siblings of children with autism or ADHD are at elevated risk for both disorders
December 16, 2018 - New project aims to understand why and how metabolic disorders develop in patients
December 16, 2018 - Diets containing GM maize have no harmful effects on health or metabolism of rats
December 16, 2018 - Are doctors and teachers confusing immaturity and attention deficit?
December 16, 2018 - Hearing loss linked with increased risk for premature death
December 16, 2018 - Chromatrap buffer reagents for lysing cells offer many benefits
December 16, 2018 - Young Breast Cancer Patients Face Higher Risk for Osteoporosis
December 16, 2018 - 3-D printing offers helping hand to people with arthritis
December 16, 2018 - Community Health Choice helps manage complex and chronic care conditions
December 16, 2018 - Regular trips out could dramatically reduce depression in older age
December 16, 2018 - CWRU to use VivaLNK’s Vital Scout device for stress study in student athletes
December 16, 2018 - ‘Easy Way Out’? Stigma May Keep Many From Weight Loss Surgery
December 16, 2018 - Gout drug may protect against chronic kidney disease
December 16, 2018 - Talking about memories enhances the wellbeing of older and younger people
December 16, 2018 - Occupational exposure to pesticides increases risk for cardiovascular disease among Latinos
December 16, 2018 - A biomarker in the brain’s circulation system may be Alzheimer’s earliest warning
December 16, 2018 - Magnesium may play important role in optimizing vitamin D levels, study shows
December 16, 2018 - The effect of probiotics on intestinal flora of premature babies
December 16, 2018 - Parents spend more time talking with kids about mechanics of using mobile devices
December 16, 2018 - Biohaven Announces Positive Results from Ongoing Rimegepant Long-Term Safety Study
December 16, 2018 - Arterial stiffness may predict dementia risk
December 16, 2018 - Study explores link between work stress and increased cancer risk
December 16, 2018 - Sex work criminalization linked to incidences of violence finds study
December 16, 2018 - Johns Hopkins researchers discover swarming behavior in fish-dwelling parasite
December 16, 2018 - Schistosomiasis prevention and treatment could help control HIV
December 16, 2018 - Early postpartum opioids linked with persistent usage
December 16, 2018 - Johns Hopkins researchers identify molecular causes of necrotizing enterocolitis in preemies
December 16, 2018 - Advanced illumination expands capabilities of light-sheet microscopy
December 16, 2018 - Alzheimer’s could possibly be spread via contaminated neurosurgery
December 16, 2018 - Unraveling the complexity of cancer biology can prompt new avenues for drug development
December 16, 2018 - Inflammatory Bowel Disease, Prostate Cancer Linked
December 16, 2018 - Cannabis youth prevention strategy should target mental wellbeing
December 15, 2018 - Recent developments and challenges in hMAT inhibitors
December 15, 2018 - Sewage bacteria found lurking in Hudson River sediments
December 15, 2018 - CDC selects UMass Amherst biostatistician model that helps predict influenza outbreaks
December 15, 2018 - Researchers reveal brain mechanism that drives itch-evoked scratching behavior
December 15, 2018 - New computer model helps predict course of the disease in prostate cancer patients
December 15, 2018 - Obesity to Blame for Almost 1 in 25 Cancers Worldwide
December 15, 2018 - How the brain tells you to scratch that itch
December 15, 2018 - New findings could help develop new immunotherapies against cancer
December 15, 2018 - World’s largest AI-powered medical research network launched by OWKIN
December 15, 2018 - Young people suffering chronic pain battle isolation and stigma as they struggle to forge their identities
December 15, 2018 - Lifespan extension at low temperatures depends on individual’s genes, study shows
December 15, 2018 - New ingestible capsule can be controlled using Bluetooth wireless technology
December 15, 2018 - Researchers uncover microRNAs involved in the control of social behavior
Scientists uncover new answers to cell aging in children with rare, fatal disease

Scientists uncover new answers to cell aging in children with rare, fatal disease

image_pdfDownload PDFimage_print

In a recent paper published in Cell Reports, Saint Louis University researchers have uncovered new answers about why cells rapidly age in children with a rare and fatal disease. The data points to cellular replication stress and a mistaken innate immune response as culprits, and the team found success in the laboratory in blocking these processes with vitamin D.

Susana Gonzalo, Ph.D., associate professor of biochemistry and molecular biology at SLU, and her lab examined human and animal cells connected to a rare disease called Hutchinson-Gilford Progeria Syndrome (HGPS).

HGPS is caused by the random mutation of a single gene that causes children to age rapidly. Children with the condition develop many of the typical changes and illness associated with aging, including hair loss, aging skin, joint abnormalities, and bone loss. The disease causes atherosclerosis — fatty deposits that clog arteries — and patients with the illness die from cardiovascular complications such as stroke or myocardial infarction in their teens.

Thanks to genetic mapping, scientists now know that HGPS is caused by a mutation in the LMNA gene, which encodes for lamin A protein. Lamin A serves as a scaffold that keeps the cell’s nucleus organized and in shape. The shortened, mutated version of this protein is called progerin, and it causes the nucleus and cell to become unstable, leading to premature aging of the cells.

“Those with progeria have a mutation in their DNA that codes for these proteins,” Gonzalo said. “The presence of progerin makes a mess in the nucleus.”

This is a problem because the nucleus houses our DNA. Cell health and reproduction are closely tied to our genome integrity — the ability of a cell to faithfully transmit its DNA information on to new cells. Mistakes or obstacles in the replication of our DNA cause breaks and mutations, which are linked to both cancer and aging.

Research in Gonzalo’s lab revealed that replication stress is a key cause of the underlying DNA damage accumulation found in the cells of those with HGPS. Replication stress occurs when the machinery that replicates DNA encounters obstacles along the way that makes replication to stall until the obstacle is removed.

Normally, our cells have in place a number of strategies to address these obstacles and then successfully continue with DNA replication. In the case of those with HGPS, however, Gonzalo found that progerin causes these strategies to falter. Replication stress can derail a cell’s ability to reproduce.

Gonzalo and her team discovered two new mechanisms by which progerin causes damage. First, progerin induces the stalling of the replication machinery, and at the same impedes the proper protection of the newly replicated DNA. This results in DNA being preyed upon by nucleases, which degrade the newly synthesized DNA with the consequent loss of genetic material.

They also found another way that progerin causes cell toxicity.

Scientists know that DNA damage and replication stress not only underlie the genomic instability that drives aging and cancer, but that they also contribute to activate inflammatory responses.

“When DNA fragments leak outside the nucleus into the cytoplasm, the cell recognizes that material as something foreign,” Gonzalo said. “This activates a series of immune responses. In particular, a signaling cascade known as the interferon response is activated when the cell thinks it senses a viral or bacterial infection that needs to be fought.

“We found that this is happening in progeria cells, and it is contributing to cellular decline.”

After demonstrating that progerin elicits replication stress and nuclease-mediated degradation of newly replicated DNA, and that it activates an interferon pathway, the team wanted to see if they could reverse these problems. They found that when they used compounds, including vitamin D, to reduce replication stress and interferon response, cellular fitness improved.

“When we block this pathway with vitamin D, it rejuvenates the cells,” Gonzalo said. “The immune response is activated by progerin and then it is brought back down by vitamin D.

“We saw that vitamin D reduces significantly the toxicity of progerin in cells from HGPS kids.”

Gonzalo hopes that her research not only will help in the eventual development of new therapies for those with HGPS, but that it also will explain many of the processes that underlie normal human aging.​

Source:

https://www.slu.edu/news/2018/march/cellular-decline-in-prematurely-aging-kids.php

Tagged with:

About author

Related Articles