Wrinkles, gray hair, illnesses... why do we age (well or badly)? A team of researchers from Nice has just provided an answer.

Wrinkles, gray hair, and especially health problems... these markers of aging are (sadly) well-known. However, what we continue to ignore are the reasons for this "decline."

Why do certain diseases (cancer, diabetes, cardiovascular diseases, etc.) become more frequent with age?

"This remains a profound biological mystery; we do not know the molecular 'start signal' of aging," says Miguel Godinho Ferreira, CNRS research director at IRCAN (Institute for Research on Cancer and Aging) in Nice.

With his team and Naz Şerifoğlu in particular, he has just uncovered a mechanism that could play this role ⁽¹⁾ . Starting from two well-established facts.

"Our telomeres, these sorts of 'caps' at the end of our chromosomes, shorten over time [read interview below]. We also know that from the age of 40-50, chronic and discreet inflammation sets in in our body. This phenomenon, called inflammaging , is associated with many age-related diseases. But until now, the link between short telomeres and low-level inflammation had not been established."

Activation of an immune pathway

To explore this link, the researchers used a model widely used to explore the molecular pathways of cancer: the zebrafish.

"We used genetically modified fish that age prematurely. At just six to nine months old, they already show visible signs of senescence—muscle weakness, reduced mobility, hunched backs, infertility, etc. Their life expectancy is reduced by a factor of four compared to wild fish. We showed, in these models, that when telomeres become too short, cells interpret this as DNA "degradation." This then triggers the activation of an innate immune defense pathway called cGAS-STING/interferon, leading to chronic inflammation with deleterious effects on the body."

Dramatic evidence of the links between short telomeres and inflammation: By blocking this inflammatory pathway, the effects of premature aging disappear.

"By inactivating the cGAS-STING/interferon pathway, we obtained fish with a radically different profile. Despite short telomeres, they lived longer, regained fertility, and retained much better tissue condition. Signs of premature aging largely disappeared."

Short telomeres, a biological timer

This work therefore establishes, in a direct manner, that short telomeres are not simple markers of aging: they are active triggers.

"They act as a biological timer: when they reach a critical threshold, they activate an alarm program, which triggers an inflammatory process, the basis of age-related diseases."

This discovery opens up new therapeutic perspectives.

"If we can selectively block this inflammatory pathway (using drugs targeting the cGAS-STING/interferon pathway, which are already being developed worldwide), it would theoretically be possible to delay or even mitigate the effects of aging; in particular, we could hope to reduce the incidence of many diseases whose frequency increases with age, including certain cancers, which thrive in inflamed tissues."

1- This research was published on June 9 in The Embo Journal, one of the best international scientific journals.