“We age because cells lose connection with each other”

A scientific team with the participation of the researcher from the medical institute RUDN Abo Kura Luay published a study on the mechanisms of aging. The work was published in the authoritative journal Biochimica et Biophysica Acta (BBA) — Molecular Basis of Disease and suggests looking at age-related diseases not as random failures, but as a systematic communication breakdown within the cell communication system.

The study also involved a team from the Institute of Aging Studies of the OSP RGNKC RNRMU named after Pirogov and the Institute of Experimental Medicine (Saint Petersburg).

Theory of the “interactome”

Imagine a huge metropolis. It has established power lines, delivery services operate, transport runs, and garbage collection crews work. As long as all services work smoothly, the city lives. But if the connection disappears, power outages occur and garbage accumulates on the streets — chaos begins.

This is roughly how Abo Kura Luay, a senior researcher at the experimental oncology laboratory of RUDN, explains the structure of our organism. The totality of all connections between cells is called the “interactome” by scientists.

“We are accustomed to thinking that we age because of the passing years. But years are just numbers in a passport. Biologically, we age because cells stop communicating effectively with each other, stop timely removing ‘waste,’ and responding properly to inflammation. In our review, we showed that all age-related diseases—from atherosclerosis to cancer—have a common root: this is a failure in the immune system’s function, which turns into chronic, low-grade inflammation.” —Abo Kura Luay.

“Zombie cells” and inflammatory substances

In youth, if a person cuts a finger or contracts a virus, the immune system reacts quickly and clearly: inflammation arises, which defeats the threat, and then subsides. It is similar to how firefighters extinguish a small bonfire and then leave.

With age, the mechanism fails. Researchers describe two key processes: immunosenescence (the immune system “wears out” and works poorly) and inflammaging (chronic, smoldering inflammation that does not subside).

The main culprits of this state are senescent cells, or, as they are figuratively called in the scientific community, “zombie cells.” They no longer divide (which protects us from cancer), but they do not die either. Instead, they release inflammatory substances: scientists call this set of signals SASP — secretory phenotype associated with aging.

“Imagine that there is an employee in the office who no longer works but constantly complains, creates noise, and poisons the life of colleagues. These are zombie cells. They force the healthy cells around to also ‘stress out’ and age. It is especially dangerous when such cells accumulate in a vessel, muscle, or brain,” —Abo Kura Luay.

Why does pain vary for everyone?

The common root (chronic inflammation) gives rise to different diseases depending on where exactly the problem “originates.”

• Heart and blood vessels (atherosclerosis). Senescent cells in the walls of blood vessels cause chronic inflammation, which leads to the formation of plaques. RUDN scientists emphasize that this is not simply a problem with cholesterol, but rather an inflammatory process, “heated up” by aging cells.
• Muscles (sarcopenia).If “zombie cells” settle in muscles, they block the regeneration of muscle tissue. A person loses strength; this is called sarcopenia. It is caused by a disruption in cell communication.
• Brain (neurodegeneration).In the brain during chronic inflammation, the problem of “garbage” is added — toxic proteins (amyloid and tau). Microglia (brain janitor cells) begin to work worse with age and instead of protection provoke inflammation, destroying neurons.
• Joints (rheumatoid arthritis).This is a vivid example of accelerated aging of the immune system, when inflammation in the joint becomes self-destructive.
• Rak.Tissue aging creates an environment in which cancer cells survive more easily. Moreover, immunotherapy, which kills cancer, can accelerate the aging of healthy cells, creating a vicious cycle.

How to “fix” aging

The most important part of the research conducted with the participation of scientist RUDN is the look into the future. If there is a common root to all diseases (cellular aging and inflammation), then treatment must be systemic.

Nowadays, medicine often works on the principle of “one disease — one pill.” But researchers propose a new strategy: to influence the fundamental mechanisms of aging in order to prevent or slow down an entire bouquet of diseases at once.

What tools are already available for this today?

• Phenolics — drugs that selectively destroy “zombie cells.” Imagine a gardener who not only waters flowers but also weeds out the weeds. Clinical trials show that a combination of drugs (dasatinib and quercetin) can improve vascular function in elderly people.
• Amplifiers Mito Ondrij. Mitochondria are the “power plants” of cells. They work less efficiently with age. Scientists are looking for ways to “recharge” them so that cells have enough energy for repair.
• Immunomodulators. Instead of suppressing the immune system (as is done in autoimmune diseases), it is necessary to carefully adjust it, removing chronic inflammation while maintaining early protection against infections.

Why 60 years is not a sentence

A researcher from RUDN and his colleagues also place great emphasis onepigenetic clock. These are modern tests that allow you to find out not the passport age, but the real biological age of a person.

“Two people of the same age can have completely different organisms. One runs marathons at 60 years old, while the other barely walks. Epigenetic clocks help to see this. Using artificial intelligence and blood analysis, we can determine how quickly a specific person is aging, and select therapy — some need senolytics, others need diet and physical exercise,” —Abo Kura Luay.

A scientist notes that we are on the threshold of a change in the medical paradigm. Instead of treating heart attacks, strokes, and cancer separately, doctors of the future will treat aging as the main disease.

“Our goal is to add life to the years. So that a person in old age remains active, clear-minded, and not a hostage to diseases. The interactome of aging is a map that will help us lay out this path,” —Abo Kura Luay.