Biological Age, Aging Clocks, and the Interplay with Lymphoid Neoplasms: Mechanisms and Clinical Frontiers.

Abstract

Lymphoid neoplasms (LN), a diverse group of malignancies arising from lymphocytes, exhibit a striking increase in incidence with chronological age, suggesting a deep connection with the aging process. While chronological age remains a primary risk factor, the concept of biological age, reflecting an individual's physiological state and susceptibility to age-related diseases, offers a more nuanced understanding of this relationship. Aging clocks, particularly epigenetic clocks based on DNA methylation, provide quantitative measures of biological age and have revealed associations between accelerated aging and increased cancer risk, including LN. Immunosenescence, the age-related decline in immune function characterized by thymic involution, altered lymphocyte populations, and chronic inflammation (inflammaging), appears to be a key mechanistic link between aging and LN development, potentially providing a more accurate predictor of cancer risk than mutation accumulation alone. Accelerated biological aging, measured by various clocks, correlates with LN risk and progression (e.g., in chronic lymphocytic leukemia), and may influence treatment tolerance and outcomes, particularly in older adults who are often burdened by frailty and comorbidities like sarcopenia. Integrating biological age assessments into clinical practice holds promise for refining diagnosis, prognosis, and personalizing treatment strategies (including guiding intensity and considering anti-aging interventions), and improving outcomes for patients with LN. This review synthesizes the current understanding of the intricate relationship between LN, immunosenescence, biological age, and aging clocks, highlighting clinical implications and key future research directions aimed at translating these insights into better patient care.