The increase in cancer cases in young people seen in recent years is related to accelerated biological aging, according to a study published this week in Nature Medicine. Identifying individuals with a biological age much higher than their chronological age may be the starting point for the development of preventive strategies, something that is increasingly feasible thanks to a better understanding of aging and the tools available to measure it at different levels (cells, organs, systems).
In recent times, numerous studies have shown the increase in various types of neoplasms in individuals under 50 years old, as published last year in Annals of Internal Medicine, which reported a significant rise in cases of leukemia and tumors of the kidney, breast, endometrium, thyroid, and colorectal. All of them, except the latter (where the increase is significantly higher among people aged 20 to 49), have also increased in those over 50 years old.
Cancer is one of the diseases most closely linked to aging because, as the years go by, cellular damage that can promote the formation of malignant tumors increases. However, it seems that a change in trend is occurring, although the emerging generational risk factors behind the increasing incidence of early-onset cancers are not yet well understood. The key is to elucidate which factors carry more weight: genetics, metabolism, lifestyle, social inequalities, environmental exposures...
Cancer does not only depend on mutations occurring in cells, confirms Maria José Sánchez, scientific director of the Biosanitary Research Institute of Granada (ibs.GRANADA), professor and head of research and consultancy at the Andalusian School of Public Health. "Mutations are important, but the biological terrain in which those cells live is also very important," affirms the director of the Cancer Registry of Granada and leader of the Ciberesp group. "It is not the same for a cellular alteration to appear in healthy tissue, with good repair capacity and immune response, as in an organism showing signs of accelerated aging."
Accelerated biological aging occurs when different systems in the body show more deterioration than expected for a person's chronological age. "This can result in more accumulated cellular damage, epigenetic changes, low-grade chronic inflammation, metabolic alterations, modifications of tissue microenvironments, reduced DNA repair capacity, and less effective immune surveillance," explains the expert. All these processes can act together, favoring the accumulation of cellular alterations and creating "a more permissive environment for already altered cells to survive, proliferate, and escape normal control mechanisms." In other words, "accelerated aging not only increases the likelihood of damage occurring but can also favor that such damage has relevant biological consequences," she emphasizes.
Uneven aging among different organs
An important aspect is that deterioration does not occur in the same way in all organs. Systemic aging is associated with a higher risk of early-onset solid tumors, especially lung cancer, gastrointestinal tumors (especially colorectal cancer), and uterine cancer. In this sense, "exploratory analyses of the study published in Nature Medicine suggest specific organ associations: immune aging is related to early-onset lung cancer and adipose tissue aging with early colorectal cancer," points out Sánchez.
This is very relevant, according to the researcher, "because it suggests that not all early-onset cancers share exactly the same mechanisms." Thus, in lung cancer, "factors such as chronic airway inflammation, immune remodeling, and certain inhaled exposures such as tobacco or pollution may weigh more," while "in colorectal cancer, obesity, metabolic dysfunction, adipose tissue-associated inflammation, and interaction with the intestinal microbiome could be especially important."
Inflammation, metabolism, microbiota...
On the other hand, Noelia Tarazona, a board member of the Spanish Association for Cancer Research (Aseica) and co-principal investigator of the Colorectal Cancer Research Group and New Therapeutic Developments in Solid Tumors at the INCLIVA Health Research Institute, explains that low-grade chronic inflammation "can damage tissues, favoring pathologies such as diabetes, cardiovascular diseases, and also some types of cancer," as reflected in the study, where "one of the markers used was C-reactive protein, reflecting systemic inflammation."
Inflammation acts as a "biological background noise," as described by Sánchez, that promotes persistent cellular damage, alters tissue repair, and creates an environment conducive to tumor development. "Although inflammation is a defense mechanism, when it persists for years, it can damage tissues and promote diseases, including cancer," Tarazona confirms.
Metabolic alterations are another crucial factor. "When there is obesity, insulin resistance, diabetes, or metabolic dysfunction, hormonal signals, growth factors, energy availability, and inflammatory pathways change," points out the scientific director of ibs.GRANADA. Adipose tissue "acts as an endocrine and immune organ, capable of modifying the biological environment in which some tumors can appear and develop."
Regarding immune dysfunction, a weakened or altered immune system reduces cancer surveillance, allowing abnormal cells to escape control and progress.
Additionally, the composition of the microbiota, which can be influenced from birth (depending on whether it is a vaginal or cesarean birth), interacts with inflammation, metabolism, and digestive mucosa, being especially relevant in colorectal cancer.
Lifestyle and social inequality
The factors mentioned do not act in isolation but form a network of mechanisms that interact in the same biological ecosystem, where elements such as lifestyle, social inequality, and exposure to various pollutants (air pollution, microplastics, pesticides, and endocrine disruptors, among others, which can interfere with hormonal, metabolic, inflammatory, and immune pathways, especially during critical developmental windows) play a role.
Lifestyle influences elements that have been shown to impact cancer risk, both in the elderly population and in younger individuals. Here, factors such as obesity, an unhealthy diet, sedentary lifestyle, chronic stress, sleep disturbances, smoking, and alcohol... should be considered.
Social inequality also has a considerable impact, according to Sánchez, who indicates that biological age "is not only the result of internal processes of the body; it also reflects the conditions in which a person is born, grows, works, lives, and ages." The place and circumstances in which a person develops their life impact "the quality of nutrition, the real possibility of physical activity, exposure to environmental pollution, the type of employment, schedules, rest, chronic stress, housing, economic security, access to the healthcare system, and prevention opportunities," emphasizes the expert.