Aging out-competes obesity, smoking, unintended exposure to carcinogens and most genetic predisposition syndromes as a leading risk factor for cancer. Despite the existence of cell-intrinsic, microenvironmental and systemic alterations or dysfunctions that commonly impact both processes, little is known about how aging and cancer are mechanistically interlinked. Such lack of knowledge can be partly attributed to the rarity or lack of human syndromes and animal models suited for the study of the aging-cancer connection, with the vast majority being optimal for investigating either cancer or aging alone, but typically not both. Adding to the lack of meaningful approaches and models, the study of cancer in the context of aging suffers from an overwhelming intrinsic complexity. This includes but is not limited to, an unavoidable latency in existing faithful models and the multiplicity of factors at play: cumulative mutations, defective immune system, aberrant microenvironmental interactions, compromised stemness, altered systemic metabolism, among others. The emergent burst in aging-focused research, empowered by recent advances in single-cell approaches and spatial resolution of omics technologies, imperatively calls for a timely think-tank to discuss the opposing and convergent forces underlying the cancer and aging connection.

The group of participants that we put together in this timely forum spans both geographical and gender diversity and includes research scientists (PhD) as well as physician-scientists (MD-PhD). Our proposal aims at joining experts from fields with traditionally limited interactions, encompassing research areas focused on human aging, mouse genetics, biochemistry, oncology, immunology, and metabolism. Only with such diverse interactions can we contribute significantly to the disentanglement of the intricate links underlying the cancer and aging association.

Critical questions in the cancer and aging arena include:

• What aspects of dysregulated systemic metabolism in aging individuals influence cancer development and response to therapy?
• Which predisposing factors have a cumulative impact, and which take place exclusively in aged individuals?
• Why are certain cancer types not associated with aging?
• Can we explain and exploit the epidemiological evidence that centenarians are protected from cancer? Can we quantify the genetic contribution to such protection?
• To what extent is an aged immune system permissive to cancer and how does it impact chemo- and immune-therapies?
• Can we improve biomarkers to predict cancer development in the elderly? Can aging biomarkers predict cancer development?

Aging is a bona fide risk factor for cancer. Yet, the mechanistic underpinnings of the aging-cancer connection remain to date, in their infancy. Slow progress in this area may be attributed to an undeniable complexity necessitating deeper understanding of the overlaps among fields of biology traditionally kept distinct. These include human and mouse genetics, epigenetics, DNA damage and repair, stemness, senescence, immunology, metabolism, among others. With recent acknowledgment of the relevance of cross-field studies in advancing cancer research and therapy- for instance the immuno-oncology interface- in addition to the emergence of new high resolution single-cell and omics technologies able to disentangle cell-cell and inter-organ cross talks, the call for a conference on the complex aging and cancer connection is novel, relevant and timely.

Our hope is for this meeting to serve both as a scientific hub and a think tank, bringing together experts from seemingly disparate fields of biology including genetics, epigenetics, cell biology, biochemistry, immunology and metabolism, to brainstorm over the overlapping, underlying mechanistic links between aging and cancer and to identify and propose novel models or approaches that can facilitate these efforts. The impact of this meeting will be far-reaching, as it will lay the grounds for continuous future collaborations with the ultimate goal of identifying strategies to prevent and treat aging-related cancers.

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