The Integrated Human System Framework: A Conceptual Model of Skin as a Biological Interface Across Health and Well-Being.

Human health and well-being are frequently examined through isolated biological or environmental determinants, an approach that constrains understanding of how internal physiology and external influences interact dynamically across the lifespan. This conceptual review introduces the Integrated Human System Framework, a biologically grounded, systems-based model that positions skin as a dynamic interface participating in and reflecting bidirectional interactions between internal systemic regulation and external environmental, behavioral, and social influences. The framework organizes intrinsic biological systems (endocrine, immune, metabolic, and neural), the skin interface, and extrinsic environmental and behavioral modulators within a vertically structured architecture, situated across lifespan-related dimensions including developmental stage, biological sex and gender, and social context. It builds on prior work critiquing organ-system fragmentation in medicine and describing mind-body-environment integration in dermatological health, extending these contributions by proposing skin specifically as a measurable, non-invasively accessible interface for systems-level investigation. Rather than replacing existing integrative approaches, including systems medicine, the biopsychosocial model, exposome science, and network physiology, the framework is positioned as complementary to them, anchoring their shared constructs in a single, biologically accessible organ system. As a conceptual framework, it provides a foundation for future empirical evaluation through interdisciplinary and longitudinal investigation using methods appropriate to the research question. Its intended contribution is to support hypothesis generation, biomarker development, integrative study design, and translational application. Potential applications include population-specific and lifespan-oriented initiatives, with the broader aim of advancing more integrated approaches to health research and clinical care.