Selection for Function in Early Life: Implications for Early-Onset Pathologies

Persistent pathological structures, such as tumors, fibrotic nodules, granulomas, microbial biofilms, or protein aggregates, are traditionally viewed as age-related conditions that emerge after reproduction, when natural selection is less effective at eliminating traits expressed late in life. However, some pathologies with robust and organized architectures can arise surprisingly early, challenging this classical perspective. We recently proposed that intra-organismal selection for function, a selective process operating within organisms and acting on non-reproducing entities by favoring structural configurations that enhance stability, robustness, and novelty generation, may play a role in aging. Here, we suggest that this same process can also operate well before the so-called selection shadow (i.e., life stages where natural selection is too weak to purge deleterious mutations). We identify three non-mutually exclusive mechanisms that may promote this early-life action: (i) initial local adaptive benefits, such as improved tissue repair or containment of infection; (ii) limited or context-specific fitness costs, allowing structurally stable but abnormal configurations to persist undetected; and (iii) rapid environmental changes that reshape tissue-level selective landscapes, driven by pollutants, endocrine disruptors, or novel diets. Recognizing early-onset organized pathologies as by-products of eco-evolutionary tissue dynamics, rather than as mere developmental errors, reframes their biological significance and opens new therapeutic avenues. Instead of targeting cells exclusively, future strategies could focus on disrupting the functional architecture of pathological tissues and structures, offering novel means to prevent or control early-life diseases shaped by internal selection forces.