Every year, viruses of the flu would infect about a billion people worldwide, according to WHO. However, not all people will react to the infection in the same way: some will be a little sick for a few days, while others will die (between 290,000 and 650,000 each year). This is particularly the case for the elderly, who represent the vast majority of fatal victims of this disease. Their weakened immune system is partly responsible for this increased risk, which is why they are advised to get vaccinated. vaccinateBut researchers at China Agricultural University have just discovered another cause: the overproduction of a protein that deactivates the immune response against infection. Their discovery, published on September 11, 2025 in the journal PNAS, opens the way to new treatment possibilities to better protect seniors.
Flu triggers mitochondrial destruction in seniors
The researchers studied the consequences of infection in 21-month-old mice (equivalent to about 65 years in humans), compared to younger mice (3 months old, early adulthood). As in humans, older individuals had more difficulty controlling the infection: these mice had higher viral loads, they lost more weight and had difficulty regaining it, lung pathology was more severe, and they died more often.
The disease's consequences were also more pronounced at the cellular level in older mice. This was particularly true of their mitochondria, organelles responsible for cellular energy production, among other functions. The infection directly attacked these essential structures, activating their destruction (through a process called mitophagy). This destructive process occurs primarily in very old cells that have already reached the stage of cellular senescence (when they can no longer divide). And this loss of mitochondria affects the immune response, promoting the virus's multiplication.
Destruction of mitochondria blocks the immune response
The destruction of mitochondria was caused by an overproduction of apolipoprotein D, involved in the transport of certain molecules, such as cholesterol. Production of this protein increases in older people, to the point that it accumulates, and some of this excess ends up in the mitochondria. Once there, it interacts with other proteins, activating mitophagy. Moreover, mice genetically modified to no longer produce apolipoprotein D do not exhibit this increased destruction of mitochondria and are more resistant to the virus. By causing the destruction of mitochondria, apolipoprotein D has an indirect impact on the production of interferons, proteins produced during infections that activate the immune response.
Killing senescent cells may protect against influenza
The overproduction ofApolipoprotein D is boosted mainly by senescent cells, which are logically more numerous in the elderly. Thus, it was possible to block this excessive production by first targeting these senescent cells with a senolytic (molecule that destroys these cells). This resulted in a safeguarding of mitochondria and the production of interferons, allowing increased protection against the virus and better survival of the mice.Preventively destroy senescent cells using natural senolytics (such as flavonoids, present in many plants, editor’s note) could therefore be protective against the flu”, launch the researchers.
Other pharmaceutical possibilities would be to target L'apolipoprotein D to prevent its accumulation in mitochondria and their destruction.Efforts are needed to test these findings in clinical trials to assess the safety and effectiveness of senolytics, mitophagy inhibitors, and drugs targeting L'“Apolipoprotein D in elderly people with viral pneumonia”, they conclude.
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