CFM organisers Alejo Efeyan (left), Maria A. Blasco and Thomas Rando. / Christian Esposito (Madmoviex). CNIO
This CNIO-CaixaResearch Frontiers Meeting brings together multiple disciplines addressing age-related diseases, which are becoming increasingly prevalent.
Therapies that apply stem cells, dietary interventions and drugs to eliminate senescent cells are key lines of research being addressed.
Cancer, cardiovascular and neurodegenerative conditions are rooted in ageing. But research in recent years has shown that ageing is not a single process but rather many different processes, and it’s time to understand how they all interact with each other. In other words, those who have discovered the puzzle pieces must now slot them together.
This was highlighted recently at the Spanish National Cancer Research Centre (CNIO) by participants in the CNIO-CaixaResearch Frontiers MeetingMolecular and Cellular Hallmarks of Aging: 3rd edition.
Jointly organised by Thomas Rando, director of the Broad Stem Cell Research Center (University of California, Los Angeles, USA), and CNIO researchers Maria A. Blasco and Alejo Efeyan, the meeting brought together around twenty speakers from Europe and the United States.
More than a decade uncovering indicators of ageing
“The ultimate goal is to treat age-related diseases, which are on the rise and for which we still do not have effective therapies, and to extend health in this stage of life,” Blasco points out.
Numerous processes contribute to ageing. The cell cleaning system stops removing toxic substances. Some cells stop dividing and remain in a state called senescence. The immune system stops recognising threats, such as the abnormal proliferation of cells that will lead to a tumour. Stem cells lose the ability to differentiate into different types of cells, and they stop regenerating tissues or organs.
These events do not occur in isolation, but that is how they have traditionally been studied. “Now we are starting to understand that there are processes that work at different levels (molecular, cellular and organ), and they all contribute to ageing,” says Efeyan.
In 2013, the pioneering study ‘Hallmarks of Aging’ was published in the scientific journal Cell, which laid the foundations for the field by identifying nine molecular indicators of ageing and suggesting potential interventions. In 2023, a review increased those indicators to twelve, measurable processes that, when manipulated, accelerate or slow down the ageing process of the body.
Strengthening the protection of chromosomes
Blasco is researching telomeres, molecular structures that protect the chromosomes. Her group at CNIO has shown that the shortening of telomeres, which occurs progressively over time, is at the root of age-related diseases such as pulmonary fibrosis.
Blasco has created a company to develop treatments for pulmonary fibrosis based on the activation of telomerase, the enzyme responsible for repairing telomeres.
This strategy, regulating telomerase, was also addressed at the conference by Steven Artandi (Stanford Cancer Institute) and Mary Armanios (Johns Hopkins University, Baltimore, USA), whose results “validate the potential use of telomerase activation to treat age-related diseases,” as indicated by Blasco.
Moving away from drugs towards more biological therapies
Cell therapies were also a central theme. Rando believes that the 21st century will be the age of cell-based therapy. He argues that stem cells “could be used to regenerate, repair or strengthen tissues throughout life”.
Ana María Cuervo (Albert Einstein College of Medicine, USA) spoke about the potential use of cellular autophagy, the process of cell cleaning and recycling, to slow down ageing and attempt to prevent the diseases it triggers.
Eileen P. White, from the Rutgers Cancer Institute, USA, is investigating cachexia, the deterioration of the body that ultimately causes the majority of cancer deaths; her goal is to “prevent it, reverse it, or generally improve patient quality of life.”
Senescent cells
It’s “inspiring”, say White and other speakers, to discover so many overlapping areas at the conference. If cachexia is related to metabolism and the immune system, and “senescent cells send messages to neighbouring cells, we cannot continue studying them as if they were isolated,” explains Efeyan, head of the Cell Metabolism and Signalling Group at CNIO.
The ability of senescent cells to promote tumour growth has been proven, and drugs called senolytics have been developed to eliminate or inhibit them. These senolytics have already reached the clinical trial phase.
Metabolism and restrictive diet
Studies in cells and animal models confirm that “food restriction is the most effective intervention to extend longevity; now we are trying to understand why,” says Efeyan. However, “it is important to be very careful when extrapolating the effects on human diet from studies on cells or animal models,” he stressed.
It is an area of intense research. Modifying metabolism through calorie restriction can affect the “interaction between cellular senescence, resilience and regeneration,” explains Adam Antebi (Max Planck Institute for Biology of Ageing, Germany).
Healthy lifestyle habits
His intervention highlighted that the response to alternating between fasting and food intake depends on age, so “intermittent fasting might be beneficial for humans at fifty, but it could be different at seventy.”
On the other hand, Pekka Katajisto (University of Helsinki, Finland) explained how a stem cell can cease to be one if its metabolism is manipulated.
Guadalupe Sabio, head of the Metabolic Interactions Group at CNIO, spoke about the benefits of exercise for metabolic health and immune response, and multiple presentations referred to nutrition.
CNIO-CaixaResearch Frontiers Meetings are prestigious international conferences on hot topics in cancer research. At these events, twenty guest speakers from around the world present their most recent findings. Another hundred experts selected for the interest of their contributions also participate in the form of posters or short presentations.