Some genetic diseases are accompanied by premature ageing, with patients developing dementia, cardiovascular disease, cancer and other diseases much earlier than expected. Now researchers have developed a database for syndromes related to premature ageing and a tool for classifying them. A researcher says that the tool enables people with such extremely rare syndromes to be diagnosed.
Some syndromes related to premature ageing (progeria) have unique manifestations. These progeroid syndromes are genetic in origin and produce typical diseases and signs of old age such as dementia, cardiovascular disease, hair loss and ageing skin – but very early in life.
Since progeroid syndromes are very rare, most doctors are not familiar with their signs, making diagnosis very difficult. Also, there is no research consensus about what a progeroid syndrome actually is.
Researchers have now developed a database of progeroid syndromes, expressed as accelerated ageing, and a tool for assessing them.
This should enable doctors to more easily diagnose people with rare progeroid syndromes and identify disorders not previously classified within the progeroid spectrum that probably should be.
“We are beginning to be able to intervene in some of these syndromes, and correct diagnosis is therefore important. In terms of research, it is also useful to learn more about the syndromes, because this can provide insight into the genes involved in their development,” explains Morten Scheibye-Knudsen, a researcher involved in developing the database and tool and Professor, Center for Healthy Aging, University of Copenhagen, Denmark.
The research has been published in Aging.
The database and tool can be accessed here.
Different types of accelerated ageing
There are many progeroid syndromes. Classical progeria, in which even children look like old men or women, is called Hutchinson-Gilford progeria syndrome. It typically affects the skin and the cardiovascular system but not the brain. Children with this syndrome often function well cognitively but look like old men or women.
Other syndromes, such as Cockayne syndrome, produce age-related changes in metabolism and accelerated ageing of the brain.
A third group of syndromes produces age-related hair loss, osteoporosis, cancer and many other conditions usually associated with ageing.
33 syndromes related to accelerated ageing
Before establishing the database, the researchers studied the literature on progeroid syndromes, identifying 33 syndromes associated with various features of accelerated ageing.
The researchers entered the syndromes and traits into the database as an analytical tool, enabling users to input various traits and then determine whether a given person has a progeroid syndrome and which one it might be.
“These syndromes are so extremely rare that doctors have little chance of recognising them and their traits unless they deal with them on a daily basis. A way to seek information based on specific patient characteristics has therefore been needed,” says Morten Scheibye-Knudsen.
Mitochondria may not be that important for ageing
The database and tool also enable researchers to determine how progeroid syndromes overlap and whether disorders not normally called progeroid syndromes have progeroid characteristics.
The researchers have already examined this and found that problems with mitochondria, a trait often associated with accelerated ageing, may not even be that important.
“The mitochondria are often considered to be a major problem in progeroid syndromes, but we found that this is only partly true. This changes our understanding of how important the mitochondria really are for these syndromes and perhaps ageing,” explains Morten Scheibye-Knudsen.
Progeroid syndromes encompass more disorders
The researchers also used the tool to investigate whether disorders currently considered outside the progeria spectrum should really be classified as progeroid syndromes.
They found that the very rare ataxia-telangiectasia-like disorder 2, spastic paraplegia 49 and Meier-Gorlin syndrome have traits that are present in other progeroid syndromes.
Ataxia-telangiectasia-like disorder 2 and Meier-Gorlin syndrome produce problems in the cells’ mechanisms for repairing DNA, and spastic paraplegia 49 produces defects in autophagy, the cellular system for eliminating defective proteins and damaged DNA. Poor autophagy means that the cells are not cleaned up, which increasingly happens with ageing.
“Problems with autophagy strongly overlap with known progeroid syndromes. This is useful because it shows that we can use the database and tool to identify syndromes with progeroid characteristics and to find new mechanisms involved in accelerated ageing,” says Morten Scheibye-Knudsen.
Potential to arrest the ageing process with medicine
As researchers learn more about syndromes in which even children end up ageing both externally and internally, potential interventions can also be investigated.
For example, researchers in Norway conducted a study in which people with ataxia-telangiectasia-like disorder 2 were treated with nicotinamide riboside, which had been shown to be able to protect brain cells in animals against neurodegeneration.
Much of the research carried out by Morten Scheibye-Knudsen formed the basis of that study.
That study had positive results and may pave the way for new interventions for people with progeroid syndromes in which neurodegeneration is a trait.
“We still have no cure for these syndromes, but we can begin to treat some of the symptoms. We can also learn more about what characterises ageing and which processes are involved. This may also help us to eventually develop interventions that can slow down the rate of ageing among otherwise healthy people,” concludes Morten Scheibye-Knudsen.
