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The Evolutionary Tug-of-War - Inflammation’s Double-Edged Sword "Environmental factors, particularly infections, have fundamentally shaped human evolution by selecting for protective inflammatory response mechanisms that enhance survival. This evolutionary pressure has created a core biological paradox: inflammation is indispensable for host defense, yet its dysregulation significantly heightens disease and mortality risk. This fundamental tension raises three fundamental questions about human aging and immunity: (1) How have selective pressures driven the evolution of mechanisms to balance inflammation's protective benefits against its harmful consequences? (2) Why does substantial variability in healthspan persist despite historically stable rates of aging? (3) Does evolutionary prioritization of reproductive fitness inherently limit longevity?" (Manoharan et. al. 2025) Let’s talk about the fire inside us. Inflammation is our body’s 911 system: lightning-fast, life-saving when a bug invades or a thorn rips skin. But leave that alarm blaring 24/7 and the fire torches the house. Evolution faced this paradox: crank the immune dial high enough to survive infection and childbirth, yet install brakes so we don’t self-destruct by 40. Manoharan’s team just mapped those brakes in 17,500 humans and called it immune resilience (IR) or the ability to fight hard, clean up fast, and stay cool afterward... and linguistic aging associations... Dr. M
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