Breaking News
April 21, 2018 - Developing cooking skills as young adult may have long-term health benefits
April 21, 2018 - Study compares survival outcomes of different drugs for type 2 diabetes
April 21, 2018 - More Than 40 Percent of Americans Breathe Dirty Air: Report
April 21, 2018 - Obstructive sleep apnea – Genetics Home Reference
April 21, 2018 - More evidence shows exposure to traffic and outdoor air pollution increases risk of asthma
April 21, 2018 - Novel gold nanoparticle technology could guide cancer treatment in real-time
April 21, 2018 - News coverage of Ebola impacted public’s perception on disease and survivors
April 21, 2018 - S.Africa’s DIY battle against HIV
April 21, 2018 - Children with autism have gastrointestinal and immune system deregulation, research finds
April 21, 2018 - Human brain processes sight and sound in the same way, shows study
April 21, 2018 - Evolutionary history of tumor helps predict severity of prostate cancer
April 21, 2018 - Pepper plant metabolizes antibiotic in personal care products
April 21, 2018 - Tradeshow Talks with Integra
April 21, 2018 - EPFL becomes part of Chan Zuckerberg’s project to develop Human Cell Atlas
April 21, 2018 - Pfizer Announces Positive Topline Results From Phase 3 ATTR-ACT Study Of Tafamidis In Patients With Transthyretin Cardiomyopathy
April 21, 2018 - Breaking through the HIV vaccine ‘logjam’
April 21, 2018 - IntelliCyt introduces new QSol buffer to enable robust, consistent sampling
April 21, 2018 - Scientists publish comprehensive lineage tree of whole adult animal in Science journal
April 21, 2018 - Innovative method based on FluidFM technology could revolutionize biological research
April 21, 2018 - Americans world’s biggest TV addicts, watching four hours a day
April 21, 2018 - Investigational drug may help increase protein levels in babies with spinal muscular atrophy
April 21, 2018 - Study shows distinctions between age groups in predicting and responding to stress at home
April 21, 2018 - Aziyo Biologics, BIOTRONIK enter into US co-distribution agreement
April 21, 2018 - Opiate Use Linked to Early Mortality in IBD Patients
April 21, 2018 - Online ads help pregnant smokers quit
April 21, 2018 - Opioid pain medications may not be safe for hemodialysis patients
April 21, 2018 - Rare variants in non-coding DNA inherited from parents heighten autism risk
April 21, 2018 - A needleless glucose monitor for diabetes patients
April 21, 2018 - BD introduces new informatics and automation solutions for clinical laboratories
April 21, 2018 - Turn Chores Into a Fitness Routine
April 21, 2018 - DNA methylation plays key role in stem cell differentiation
April 21, 2018 - Scientists find link between soil metals and cancer mortality
April 21, 2018 - Experts discuss implications of low calcium intake in global population
April 21, 2018 - GNA Biosolutions to display Pharos V8 Laser PCR instrument at Analytica trade fair
April 21, 2018 - People with vitamin D deficiency may be at greater risk of diabetes
April 21, 2018 - Study findings could open new possibilities for treating cancer with adenovirus
April 21, 2018 - People who use medical marijuana have higher rates of prescription drug use, study finds
April 21, 2018 - Study debunks ‘myth’ that strenuous exercise dampens immunity
April 21, 2018 - FDA approves marijuana based medication for epilepsy treatment
April 21, 2018 - Researchers find novel genes for longevity in mammals
April 21, 2018 - GNA Biosolutions and project partners launch new research project to develop TB diagnostic platform for POC applications
April 21, 2018 - $2 million funding boosts progress of UAB biomedical startup
April 21, 2018 - Scientists identify gene responsible for evolution of recombination rates
April 21, 2018 - UConn researchers develop new composite for healing broken load-bearing bones
April 21, 2018 - Study examines how higher-order gene combinations help maintain normal cell physiology
April 21, 2018 - Study challenges use of whole-brain radiation for small-cell lung cancer patients with brain metastases
April 21, 2018 - Researchers discover blood biomarkers that may help detect, confirm mild traumatic brain injury
April 21, 2018 - People who become physically active after heart attack more likely to live longer, shows research
April 21, 2018 - CPRIT awards $2 million grant to push forward breast cancer research in West Texas
April 21, 2018 - Unhealthy diet damages the development of immature fat cells, study shows
April 21, 2018 - Consumption of protein supplements with meals may provide better weight control
April 21, 2018 - 4 Types of Foods to Help Boost Your Memory
April 21, 2018 - How did gonorrhea become a drug-resistant superbug?
April 21, 2018 - DePuy Synthes announces clinical results related to use of CORAIL Hip System Femoral Stems
April 21, 2018 - New initiative launched to support goals of Human Cell Atlas
April 20, 2018 - Teen patient gets a new lease on life
April 20, 2018 - Cancer Australia launches new framework to improve outcomes for lung cancer patients
April 20, 2018 - ‘Gut-on-a-chip’ model recreates intestinal matrix critical for nutrient absorption
April 20, 2018 - Researchers develop new drug-testing platform for epilepsy
April 20, 2018 - FDA Alert: NxtGen Botanicals Maeng Da Kratom by NGB Corp.: Recall
April 20, 2018 - Pelizaeus-Merzbacher-like disease type 1 – Genetics Home Reference
April 20, 2018 - Tick-borne diseases reach epidemic levels, panel says
April 20, 2018 - A potential “male pill” without side effects
April 20, 2018 - Researchers discover new information related to rare form of leukemia
April 20, 2018 - Researchers find crucial links between dopamine and avoidance behavior
April 20, 2018 - UGA scientist creates system for efficient detection of foodborne pathogens
April 20, 2018 - Social Support of Autonomy Tied to Better Glycemic Control in DM
April 20, 2018 - Study reports use of nutritional ketosis with mobile app intervention could reverse Type 2 diabetes
April 20, 2018 - New microscopy techniques allow quasi-biochemical studies on living T cells
April 20, 2018 - Study shows connection between muscular strength and brain health
April 20, 2018 - Ecolab introduces Life Sciences cleanroom program in North America
April 20, 2018 - Normal weight people with fat belly may have more chance of heart problems
April 20, 2018 - Male fruit flies like sex and alcohol
April 20, 2018 - Meditation could help reduce anxiety levels and some heart health risk factors
April 20, 2018 - Improving job prospects unlikely to control opioid epidemic
April 20, 2018 - Skin Sensor Might Someday Track Alcoholics’ Booze Intake
April 20, 2018 - The relevance of GABA for diabetes highlighted in two new studies
April 20, 2018 - Novel method enables fast and noninvasive assessment of tumor status
April 20, 2018 - IU psychologist receives NIH grant to study earliest phases of language learning in children
April 20, 2018 - Walking fast lowers risk of hospitalization in heart patients, shows study
Researchers reveal molecular structure of ‘anti-aging’ protein

Researchers reveal molecular structure of ‘anti-aging’ protein

image_pdfDownload PDFimage_print

Researchers from UT Southwestern’s Charles and Jane Pak Center for Mineral Metabolism and Clinical Research and Internal Medicine’s Division of Nephrology recently published work in Nature that reveals the molecular structure of the so-called “anti-aging” protein alpha Klotho (a-Klotho) and how it transmits a hormonal signal that controls a variety of biologic processes. The investigation was performed in collaboration with scientists from New York University School of Medicine and Wenzhou Medical University in China.

Studies at UTSW two decades ago by Dr. Makoto Kuro-o, Professor of Pathology, demonstrated that mice lacking either a-Klotho or the hormone FGF23 suffered from premature and multiple organ failure as well as other conditions, including early onset cardiovascular disease, cancer, and cognitive decline. Because defects in a-Klotho lead to symptoms seen in aging, researchers inferred that a-Klotho suppresses aging, leading to great interest in how the a-Klotho protein might work together with the hormone FGF23 to fulfill their roles.

a-Klotho can exist on the surface of a cell or can be released from the cell and circulate in body fluids, including the blood, as soluble a-Klotho. The cell-attached form and the circulating form of a-Klotho were previously and universally believed to serve completely different functions.

“The a-Klotho gene [then called Klotho] was cloned by Dr. Kuro-o in 1997 shortly before he was recruited here, and during his tenure at UT Southwestern he has carried out the most seminal work in this field,” said Pak Center Director Dr. Orson Moe. “The gene protects against many diseases, including cardiovascular disease, cancer, diabetes, aging, neurodegeneration, and kidney disease. The structure of the a-Klotho protein and how the protein functions, however, largely remained a mystery until this current work.”

By providing a first look at the structure of the protein complex that includes FGF23 and its co-receptors, the FGF receptor and a-Klotho, the most recent study challenges the long-accepted belief that only the cell-attached form of aKlotho can serve as a receptor for FGF23 and hence that FGF23 action is restricted to tissues having the cell-attached form.

Study authors include Dr. Moe, Professor of Internal Medicine and Physiology, and Dr. Ming Chang Hu, Associate Professor of Internal Medicine and Pediatrics. Dr. Moe holds The Charles Pak Distinguished Chair in Mineral Metabolism, and the Donald W. Seldin Professorship in Clinical Investigation. Dr. Hu holds the Makoto Kuro-o Professorship in Bone and Kidney Research.

One of the major, paradigm-changing findings revealed by solving the protein complex structure is that the circulating form of soluble a-Klotho can actually serve as a co-receptor for FGF23. Thus, the soluble form of a-Klotho can go to any cell in the body and act as a co-receptor for FGF23, rendering every cell a possible target of FGF23, representing a major paradigm shift.

“a-Klotho researchers in cancer, aging, neurologic, cardiovascular, and kidney disease will benefit from this research,” Dr. Moe said. “The knowledge of the structure of the protein, along with its molecular binding partners, will enable us to greatly advance the understanding of how a-Klotho works and also how to best design therapeutic strategies and novel agents that can either activate or block FGF23-a-Klotho interaction and signaling as needed.”

Collaboratively led by NYU School of Medicine structural biologist Dr. Moosa Mohammadi, the investigation included researchers from UTSW, the Rockefeller University-based New York Structural Biology Center, and Wenzhou Medical University.

The study provides evidence for how FGF23 signals to cells by forming a complex with a-Klotho and the two other molecular partners. Made by bone cells, the FGF23 hormone travels via the bloodstream to cells in all organs, where it regulates many aspects of mineral metabolism. Abnormal FGF23 levels are found in many disease states. In chronic kidney disease, for example, high FGF23 levels are believed to cause many of the disease’s complications and fatalities.

The researchers say their findings also shed new light on how kidney disease leads to an abnormal thickening of heart muscle tissue called hypertrophy, which is a leading cause of death in people with kidney disease caused by high blood pressure, diabetes, and other illnesses. When damaged kidney tubules can no longer eliminate phosphate in the urine, FGF23 rises, initially as an effort to keep blood phosphate in check. With time, FGF23 can rise to harmful levels.

A prevailing hypothesis has been that very high levels of FGF23 cause hypertrophy in the heart. But the theory remained controversial because heart tissue does not have a-Klotho, which must be present if FGF23 is to signal. The latest findings indicate that a-Klotho can be “delivered” through the bloodstream to organs where it is not normally present. This could potentially launch drug development programs for kidney disease, the researchers said.

“The solution of this protein structure will guide many future studies,” Dr. Moe said. “There are numerous diseases that involve a-Klotho deficiency. Replenishment of a-Klotho by either recombinant protein injection or drugs that increase a patient’s own a-Klotho will have potential therapeutic implications for neurologic, metabolic, cardiovascular and kidney disease, and cancer.”

Source:

http://www.utsouthwestern.edu/newsroom/articles/year-2018/anti-aging-protein.html

Tagged with:

About author

Related Articles