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Chronic inflammation, a driving force behind tumor initiation and progression, is central to understanding the biology of cancer, as is the concept of inflammaging—the chronic, low-grade inflammation associated with aging.
Cancer represents a growing global health challenge that is fueled by aging populations and increasing life expectancy. According to the World Health Organization, cancer-related deaths reached nearly 10 million in 2022, and approximately 20 million new cases were detected. These figures represent a 25% rise in deaths and new cases compared to the previous decade, underscoring the escalating burden of disease worldwide.
Although there is no singular cause attributable to the development of cancer, there is a stark demographic shift in incidence toward aging individuals. By 2030, an estimated 70% of all cases will present in individuals 65 years or older. Moreover, central to understanding the molecular biology of cancer is its relationship with chronic inflammation, a driving force behind tumor initiation and progression. The connection between these factors is exemplified by a concept called inflammaging—the chronic, low-grade inflammation associated with aging.
In May 2024, The New York Academy of Sciences hosted an educational symposium entitled Cancer and Aging - The Inflammaging Connection. During the event, speakers at several keynote and plenary presentations attempted to answer the question, “Why have humans been so good at not getting cancer in the first 4 to 5 decades of life?” Potential answers to this question and the intricate molecular links between aging, inflammation, and cancer are explored below.
Inflammaging describes the chronic, low-grade, inflammatory state that arises in the absence of infection and persists as a hallmark of aging. This condition is promoted by the activation of signaling pathways such as those regulated by the NF-κB transcription factor. Additionally, inflammaging is sustained by a variety of stimuli including cellular senescence, metabolic inflammation, gut microbiota dysfunction, and nutritional influences. These factors compound their influence over time and hit a watershed moment around midlife.
Chronic inflammation is central to the development of cancer from initial tumor formation to metastatic spread. Inflammatory cells within the tumor microenvironment release factors that lead to (epi)genetic instability, cellular proliferation, and angiogenesis—all conditions that promote cancer growth. The inflammaging process exacerbates these conditions, creating a systemic pro-inflammatory state that intensifies with cellular and tissue aging.
This phenomenon is characterized by elevated levels of circulating inflammatory mediators such as interleukin-6 (IL-6), IL-1, TNF-α, and C-reactive protein. These markers are not only indicators of aging, but also predictors of age-related medical conditions that include cardiovascular disease, type 2 diabetes, Alzheimer’s disease, and cancer. The imbalance between pro-inflammatory and anti-inflammatory mediators underpins the conditions for disease development that affect tissues, organs, and immune function alike.
Inflammaging acts as a double-edged sword: it accelerates the normal biological aging process while also amplifying the risk of diseases linked to advanced age. For patients with cancer, inflammaging complicates prognosis by compounding inflammatory processes in the tumor microenvironment while simultaneously diminishing overall health. Elevated levels of inflammatory markers (eg, CRP, IL-6) have been identified as independent prognostic factors in various cancer types. A 2024 study identified a cancer inflammaging score as a potential prognostic tool.
Although inflammation plays a beneficial role as a transient immune response to infection and during wound repair, it becomes maladaptive with age, leading to chronic tissue dysfunction, degeneration, and disease. Fortunately, the inflammaging process can be mitigated through long-term lifestyle interventions such as a nutritious diet and regular physical exercise. Counteracting the inflammaging process extends beyond the pursuit of cancer prevention and treatment—it represents a broader commitment to fostering healthier, more resilient aging for all individuals and future generations.
Nicole A Colwell, MD, is a senior editor/medical writer for the Association of Cancer Care Centers (ACCC).
