“Humans and their predecessors evolved in environments where they were challenged intermittently…Cells and organ systems acquired and retained molecular signaling and metabolic pathways through which the environmental challenges enhanced the functionality and resilience of the cells and organisms…Within the past 60 years there has been a precipitous diminution of such challenges in modern societies…Signaling pathways that mediate beneficial effects of environmental challenges on health and disease resistance are disengaged, thereby rendering people vulnerable to obesity, diabetes, cardiovascular disease, cancers and neurodegenerative disorders.”