How somatic mutations cause aging without causing aging

Evolutionary theory identifies reduced extrinsic mortality as driving the evolution of slower aging, but there is no consensus about what, if anything, impedes the evolution of increased longevity. Classic mechanisms such as antagonistic pleiotropy and resource al-location efficiency fail to identify the specific molecular mechanisms determining life span. The tumor suppression theory of ageing is a reductionist evolutionary theory of ag-ing proposing cancer risk as the dominant force preventing indefinite self-renewal and constraining the evolution of longevity in mammals. In this work, most hallmarks of agingare shown to be tumor suppressors and rearranged into a causal hierarchy that puts for-ward cell proliferation as the primary driver of aging. Tumor-suppressive hallmarks like telomere shortening, cellular senescence and others restrain malignant transformation, and this benefit explains why they are extensively interconnected. The resulting stem cell exhaustion constitutes the proximate mechanism of aging, the store of biological age and characterizes the state of being old. Somatic mutations are therefore the ultimate reason why we age, but not the proximate mechanism how we age, which is exhaustion of stem cell reserves. The idea that tumor suppression contributes to aging originated several dec-ades ago, but was abandoned largely because caloric restriction (CR) and interventions into conserved aging pathways delay both aging and cancer, contradicting the idea. By explaining how CR slows aging through the regulation of cell proliferation rates, the tumor suppression theory of aging resolves this conundrum and identifies the instability of DNA giving rise to cancer as the ultimate reason why we age and the primary factor constrain-ing the evolution of very long, if not indefinite, lifespans in larger animals. The tumor sup-pression theory of aging traverses the interdisciplinary divide by providing both an evolu-tionary reason why we age as well as its molecular mechanism by reinterpreting most hallmarks of aging as interconnected tumor suppression mechanisms that evolved to con-tain cancer risk. References: Wolf, A. M. (2021) The tumor suppression theory of aging. Mechanisms of Ageing and Development 200, 111583. Wolf, A. M. (2021) Rodent diet aids and the fallacy of caloric restricƟon. Mechanisms of Ageing and Development 200, 111584. Wolf, A. M. (2025). How somatic mutations cause aging without causing aging. doi.org/10.5281/ze-nodo.15665025