Unravelling the enigma of the complex relationship between aging, senescence, molecular biomarkers and sex/gender influences: a roadmap of open questions

The intricate network among senescence, molecular biomarkers and sex/gender influences captivates the scientific community and offers profound insights into the complexities of the aging process. We navigate through the current state of knowledge in this intriguing field, focusing on the various questions still open. Aging, as a holistic process, involves a myriad of molecular changes at the cellular, tissue, and systemic levels. The identification of reliable molecular biomarkers holds promise for tracking and understanding the aging process. However, challenges persist in the establishment of universally applicable biomarkers that accurately reflect biological age. Senescence, a hallmark of aging, represents a multifaceted process marked by permanent cell cycle arrest. Despite significant advances in knowledge of molecular mechanisms underlying senescence, several outstanding questions persist. What are the molecular triggers priming senescence? How do they vary across different cell types and tissues? Understanding the origin of heterogeneity in senescent cells and its effect on tissue dysfunction is a pressing question that needs to be fully addressed. The impact of biological sex on aging introduces a layer of complexity that demands further exploration. While it is recognized that sex-specific factors influence aging trajectories, the underlying molecular mechanisms remain elusive. How do sex-specific factors modulate senescence, and to what extent do they influence the molecular signatures associated with aging? Unravelling these mysteries will help to develop targeted interventions that account for sex/gender-specific distinctions in aging. The integration of senescence, sex/gender, aging, and molecular biomarkers raises critical questions about the interplay between all these elements. The attempt of addressing these questions will allow to advance our understanding of the aging process, paving the way towards tailored preventive treatments and a more personalized approach to healthy aging in men and women.