Several factors lead to cognitive decline as we get older. At the level of the neuron, it is the cell itself that suffers. “Connections between neurons diminish, dendritic spines are altered and memory deteriorates, neuroinflammation sets in in the brain,” describes Lida Katsimpardi, Inserm researcher in the biology of aging, currently at the Institut Necker Enfants Malades and the Institut Pasteur.
“At the same time, there is a decline in astrocytes that supply nutrients and blood-borne trans-oxygen. And the blood vessels narrow and therefore carry even less oxygen, fewer nutrients… It’s a bit of a general dysfunction that sets in!”
> Read also: Simple gestures to preserve memory
“Aged” blood contains factors that contribute to cognitive decline… what about “young” blood?
Aging is accentuated in the presence of chronic stress, obesity, disease… which is important to take into account because, “When a vital organ, far from the brain, has a problem, it secretes factors that will be transmitted by the blood. They will go directly inside the brain or, if they do not cross the blood-brain barrier, they will induce changes in the endothelial cells. [qui contrôlent le tonus vasculaire en sécrétant divers agents vasoconstricteurs ou -dilatateurs, NDLR]. These will then decrease the nutritional intake and the oxygen supply. to neuronsexplains the neurobiologist.
An idea emerged from this observation: just as “aged” blood can carry factors that accelerate cognitive decline, could “young” blood contain the elixir of youth of neurogenesis?
The GDF-11 molecule has an effect on metabolic change
SHIPS REMODELED
In 2014, a team of researchers in Harvard University’s Department of Stem Cells and Regenerative Biology, including Lida Katsimpardi, attempted heterochronic parabiosis in mice (Science , May 2014). In concrete terms, the blood network of a 2-month-old mouse was linked via a graft to that of a 21-month-old mouse – the life span of a mouse is 27 months.
Control groups were also formed by matching age-matched mice, two juveniles and two adults. After five weeks, blood from the 21-month-old mouse affected the olfactory neurogenesis (responsible for olfactory memory) of the two-month-old mouse. In contrast, that of the aged mouse had improved, as had the vascularity and blood flow of its neurogenic niche.
This little miracle has a name: GDF-11, a molecule involved in embryonic development, very present in the blood of young mice. To confirm the action of GDF-11, 23-month-old mice were treated for four weeks with daily injections of GDF-11 serum.
“We found that the GDF-11 molecule has an effect on metabolic change and can slow or even reverse – although the word seems a bit strong – aging. Blood vessels remodel themselves: they are dilated while they tend to shrink with age [le volume sanguin des souris a augmenté de 50 %, ]. This is also an interesting point about it neurodegenerative diseases such as Alzheimer’s, which are linked to the deterioration of blood vessels”explains Lida Katsimpardi.
In 2019, joining the Institut Pasteur’s Perception and Memory Unit, she went further by noting that mice given GDF11 lost weight, without their appetites being altered. GDF-11 therefore also has a calorie restriction effect, the effect of which on organ rejuvenation has been proven. These discoveries pave the way for new therapeutic uses for human neurodegenerative diseases, but also metabolic diseases such as obesity.
