The guardian paradox: DNA damage response overactivation as an integrative driver of aging - a tumor suppressor-negative regulator framework.

Patrick E Sewell¹

¹Triple Helix Science, Santa Ana, CA 92705, USA.

Abstract

Aging is multi-causal, yet its molecular hallmarks may converge on a few upstream integrating nodes. We advance the hypothesis that chronic, largely mutation-independent overactivation of the DNA damage response (DDR) is one such node, dysregulating the cell's intact guardian pathways-the tumor-suppressor networks and their negative regulators-to induce senescence, deplete stem-cell pools, and dri…

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