Would you like to live to be 100? What about if you could reach 100 years of age knowing that you would not suffer from obesity, diabetes, increased blood pressure, and abnormal cholesterol?
Europe’s population is ageing, and we are living for longer than ever before. By 2060, one third of the European Union’s population will be over 65, according to the 2021 Ageing Report.
However, quality of life decreases as we age, in part due to metabolic dysfunction. High blood pressure, cholesterol, high blood sugar and growing waistlines also make us more susceptible to heart disease, stroke and type 2 diabetes.
As a growing number of people live longer, this will put a strain on European healthcare systems. Increased longevity without improved quality of life means people will depend on healthcare services for longer time periods, but if we could age without suffering from the metabolic conditions that cause many age-related diseases, this extra pressure – and the associated cost for the taxpayer – could be avoided.
Michela Matteoli
Prof. Michela Matteoli, Head of the Neuro Center at Humanitas Research Hospital, Professor at Humanitas University and Director of the CNR Institute of Neuroscience, recently won an ERC Advanced Grant for the MATILDA project. It aims to target tiny immune cells called microglia and a protein called TREM2 in the brain to investigate whether they have an influence on metabolic function.
If successful, the research could lead to the development of drugs that would, in essence, halt the onslaught of unwelcome metabolic side effects that come with getting older.
The idea for this project builds on Prof. Matteoli’s past achievements, spanning more than 25 years.
“I was interested in addressing at a molecular level the impact of the immune system at the synaptic level”
The formation of synapses, which are the gaps across which two neurons communicate, has been shown to be highly important in whether or not a person develops autism or schizophrenia.
A person has the maximum number of synapses in the brain when they are aged between 3 and 4. Then, up until the age of 22-23, the brain systematically eliminates the excess synapses, in a process called synaptic pruning. Too many or too few synapses left may lead to autism or schizophrenia.
Prof. Matteoli’s team discovered that a protein called TREM2 was vital for the process of synaptic pruning.
In the brain TREM2 is expressed in microglia, the brain immune cells, and it is crucially involved in the control of brain inflammatory responses.
“We found that in the absence of TREM2, microglia are unable to correctly perform the elimination of supernumerary synapses, this has important consequences on the formation of brain circuits”
In the experiments conducted, they showed that the circuits of the brain become completely disrupted if TREM2 is missing. Examination of brains from people with autism backed up those results – brains aged between 2 and 22 showed significantly lower levels of TREM2.
TREM2 is found within the microglia in the hypothalamus, which is the centre of regulation for metabolism throughout the whole body. TREM2 and microglia could be crucial here: synapses and circuits found in the hypothalamus orchestrate food intake and energy expenditure. Also, inflammation in the hypothalamus causes nutritional and body weight changes as well as systemic glucose intolerance. Moving on from her earlier work, Prof. Matteoli figured that disruption of TREM2 in the microglia of the hypothalamus could impact hypothalamic synapses and inflammatory states, having a hefty impact on metabolic processes throughout the whole body, even for healthy individuals.
Our metabolism involves all of the chemical and biological reactions that transform food into energy within our bodies. Metabolic disorders refer to anything that disrupts those processes – and while some of these disorders are inherited, like an inability to process iron correctly, others, like diabetes, can be developed throughout our lives.
The inability to process glucose correctly, together with high blood pressure and high cholesterol make it difficult to transform our food into energy efficiently, and can result in more severe consequences including diabetes and stroke.
But if Matteoli’s research is successful, it could show that simply flipping a switch in our brains could make us less susceptible to these risks as we grow older.
In essence, a drug could be developed that could regulate TREM2 more efficiently, ensuring that synapses and circuits are correctly controlled and that our metabolic processes are not disrupted during ageing.
Eurostat predicts that there will be half a million centenarians in the EU-27 by 2050, yet if gains are made in longevity without similar strides in quality of life, then living longer is not such an attractive option. Research like Matteoli’s could improve those final years dramatically, enabling us to live into old age but in a healthy way.
Promoted Content by Humanitas Research Hospital
