Study in Twins Links Age-Related Changes in DNA Methylation with ALS

Study in Twins Links Age-Related Changes in DNA Methylation with ALS

A study in identical twins or triplets found that changes in DNA marks, collectively known as DNA methylation and typically associated with aging, can like genetics play an important role to determining the development of amyotrophic lateral sclerosis (ALS).

The four sets of ALS-affected and unaffected siblings carried age-related differences in methylation patterns across the genome (the complete set of genes or genetic material present in an organism), the researchers report. They also identified genes that may explain why some people are more susceptible or more resistant to the disease, and may help identify targets for possible treatment.

The findings were described in the study “Monozygotic twins and triplets discordant for amyotrophic lateral sclerosis display differential methylation and gene expression,” published in the journal Scientific Reports.

Amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, is a progressive neurological disease that causes gradual destruction of motor neurons, which control voluntary muscle movement.

ALS has variable manifestations, including age, site of onset, and disease duration, but two common forms: sporadic ALS, which accounts for about 90 percent of ALS cases marked by the disease’s cause not being well-understood; and familial ALS, caused by mutations at certain genes inherited from a parent.

Some studies suggest that beyond mutations, other kinds of genetic changes can influence a person’s susceptibility to ALS.

Research looking at the whole methylome (the entire set of DNA methylation marks across the genome), and transcriptome (gene readouts across the whole genome) in spinal cord tissue and blood have found global changes. That work implicated various genes and biological pathways, including immune responses and transport within cells.

DNA methylation refers to the attachment of a chemical group (methyl group) to DNA. This type of DNA modification is called epigenetic, which means it does not change the DNA sequence itself but can affect gene activity. For instance, the presence of a methyl mark can turn a gene “off” and stop it from driving the production of a protein.

Researchers here compared the methylome and transcriptome of identical (monozygotic) twins and triplets — some of whom developed ALS while others had not.

Identical twins share the same genome; that is, they have the same DNA sequence for all genes. For many years scientists have been studying twins to find out which genetic mechanisms beyond inherited genes — such as DNA methylation and gene activity — contribute to human traits and disease.

The four pairs studied represented both sporadic ALS (one pair of male and one of females twins) and twins with most common types of familial ALS, linked to C9orf72 (one twin pair) and to SOD1 (one triplet) mutations. In each pair of twins or triplets, only one individual had ALS.

Researchers analyzed methylome and transcriptome data, independently and in combination, in an attempt to identify disease-relevant changes and their potential impact on the disease.

Results showed a significant interaction between age, disease status and methylation, with older twins showing consistent differences in DNA methylation between ALS-affected and unaffected co-twins.

Age-associated changes in DNA methylation, also known as DNA methylation age, are well-documented and thought to promote such diseases of aging as cancer. Recent studies also have identified groups of individual methylation sites across our genome, which trace with chronological age and are referred to as the DNA methylation clock.

Data now gathered suggest this pattern, DNA methylation age, is also an important factor contributing to ALS.

By comparing gene activity and DNA methylation changes across all twin and triplet sets, the researchers also identified several genes likely to influence ALS, either by contributing to or protection from disease. “These genes and pathways offer potential targets for future therapeutic treatment for ALS,” they wrote.

The findings suggest that people with ALS appear to carry changes in gene activity (transcriptome changes) and DNA chemical marks (epigenetic changes) important for determining disease that may be highly complex and affect different pathways, and only some of which are shared among patients.

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.
×
Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.
Latest Posts
  • mexiletine trial als
  • ANXA11
  • glutamate signaling
Average Rating
0 out of 5 stars. 0 votes.
My Rating:

2 comments

  1. Charles B. McDermott says:

    I am an identical twin who’s twin is suffering terribly from ALS. I would be willing to join any study which could help my twin, or any other twins from this terrible disease. I believe that my twin would be willing as well, if he is able.

  2. This study is wonderfully empowering and long-overdue. The fact that it is coming out of Australia and not the USA is pathetic, considering the massive amounts of money that have been poured into the USA research programs and charities.
    While Authors did not interpret the significance of these findings, I can. Methylation is something that is within the reach of patients today (both preventatively and during pathological states as a disease modifier). Other clinical studies (in humans affected by ALS) support these findings. Multiple studies confirm the life-extending properties of methylcobalamin injections (a methyl-donor that directly impacts the central nervous system (CNS), unlike other forms of cobalamin / vitamin B-12). Other cofactors support its metabolism, so imagine the possibilities of a complete cocktail…
    Methylcobalamin is just one CNS methyl-donor that serves multiple critical functions in the nervous system. There are more.
    Methylation is not a complete picture of this complex disease (but, it is plainly an important modifier). There is still a need for a complete cocktail (including an emphasis on gene therapy for some subsets of ALS and other multi-functional disease-modifying compounds, like methylcobalamin, that are already available today and are not marketed as a drug).
    Personally, I would like to see a call-to-action. Non-profit dollars and grants must be put in place to insight reform for complete insurance (including Medicare and Medicaid) coverage of compounded medications like methylcobalamin and other disease-modifying compounds currently available over-the-counter (stabilized enhanced industry standard of RLA, acetyl-L-carnitine, methyl-folate, standardized lipid-soluble enhanced curcumin, etc.).
    How many people will suffer in the most inhumane ways before there is reform? Get onboard, ALS Associations and ALS TDI! A simple google search will find ALS patients winning their fight through methylation and more! Hiding behind sophisticated science is only lining your pockets. It’s really about emphasis and dollars allocated appropriately.

Leave a Comment

Your email address will not be published. Required fields are marked *