About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Epigenetic Changes in Aging can Protect Risk of Alzheimer's Disease

by Hannah Joy on March 6, 2018 at 12:26 PM
Font : A-A+

Epigenetic Changes in Aging can Protect Risk of Alzheimer's Disease

Epigenome alterations may occur much early and a link between aging and Alzheimer's disease (AD) has been found, which aids in drug development.

Although certain genetic variants increase the risk of AD, age is the strongest known risk factor. But the way in which molecular processes of aging predispose people to AD, or become impaired in AD remains a mystery.

Advertisement


A team of researchers from the Perelman School of Medicine at the University of Pennsylvania, publishing in Nature Neuroscience, profiled the epigenomic landscape of AD brains, specifically in one of the regions affected early in AD, the lateral temporal lobe. They compared these to both younger and elderly cognitively normal control subjects.

The team described the genome-wide enrichment of a chemical modification of histone proteins that regulates the compaction of chromosomes in the nucleus (called acetylation of lysine 16 on histone H4, or H4K16ac for short).
Advertisement

Changes to the way H4K16ac is modified along the genome in disease versus normal aging brains may signify places for future drug development. Because changes in H4K16ac govern how genes are expressed, the location and amount of epigenetic alterations is called the "epigenetic landscape."

"This is the first time that we have been able to look at these relationships in human tissue by using donated postmortem brain tissue from the Penn Brain Bank," said Shelley Berger, PhD, a professor of Cell and Developmental Biology in the Perelman School of Medicine and a professor of Biology in the School of Arts and Sciences. "Our results establish the basis for an epigenetic link between aging and Alzheimer's disease."

Berger, also the director of the Penn Epigenetics Institute, Nancy Bonini, PhD, a professor of Biology, and Brad Johnson, MD, PhD, an associate professor of Pathology and Laboratory Medicine, are co-senior authors of the new study.

H4K16ac is a key modification in human health because it regulates cellular responses to stress and to DNA damage.

The team found that, while normal aging leads to increasing H4K16ac in new positions along the genome and an increase in where it is already present, in great contrast, AD entails losses of H4K16ac in the proximity of genes linked to aging and AD.

In addition, the team discovered an association between the location of H4K16ac changes and genetic variants identified in prior AD genome-wide association studies. A three-way comparison of younger, older, and AD brain tissue revealed a specific class of H4K16ac changes in AD compared to normal age-established changes in the brain. This finding indicates that certain normal aging changes in the epigenome may actually protect against AD and when these goes awry, a person may become predisposed to AD.

"These analyses point to a new model of Alzheimer's disease. Specifically it appears that AD is not simply an advanced state of normal aging, but rather dysregulated aging that may induce disease-specific changes to the structure of chromatin - the combination of histone proteins and DNA." said first author Raffaella Nativio, PhD, a postdoctoral fellow in Berger's lab.

Accumulation of intercellular amyloid plaques and neurofibrillary tangles are the two hallmarks of AD that drive the death of neurons and the corresponding loss of cognitive abilities. However, expression of plaques and tangles is very late in the development of AD, while epigenome alterations might occur much earlier and represent targets to attack with medications.

The authors emphasized that this study does not suggest a cure for AD, but rather the possibility of finding ways to prevent nerve cell death and enhance the quality of aging. Their upcoming experiments aim to discover the physiological changes that cause the decrease of H4K16ac specifically in AD brains, but not in normal-aged brains.



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
Health Benefits of Giloy
Breast Cancer Awareness Month 2021 - It's time to RISE
First-Ever Successful Pig-To-Human Kidney Transplantation
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Ageing and Sleep Epigenetics Telomere Shortening And Ageing 

Recommended Reading
New Epigenetic Compounds Show Promise in Patients With Lymphoma
Compounds targeting epigenetics namely BET inhibitors and EZH2 inhibitors show promising results in ...
Important Epigenetic Regulation Mechanism Identified
DNMT3A,one of the frequently mutated genes in an aggressive leukemia also plays a significant role ....
Role of Epigenetics in Preeclampsia
Upregulation of DLX5 gene due to loss of imprinting triggers other preeclamptic genes that result .....
Epigenetic Influences of Chronic Pain Explored
One protein with a critical role in mediating epigenetic changes is methyl-CpG-binding protein 2 ......
Ageing and Sleep
Sleep is a barometer of good health in the elderly. Sleep problems in the elderly are controlled by ...
Epigenetics
In the recent years ‘epigenetics’ represents inheritable changes in gene expression that do not incl...
Telomere Shortening And Ageing
Telomeres are cap- like structures at chromosome ends that play an important role in ageing and in t...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use