tories of allostatic load. It is, in fact, such early precursors that are believed to initiate the cumulative physiological wear and tear that the concept of allostatic load is intended to capture. Investigations along these lines will require increased assessment of co-occurring components of physiological risk (e.g., function of the cardiovascular system, the HPA axis, sympathetic nervous system function, metabolic risk, immune function) early in life as well as their long-term sequelae in later life comorbidity.
A basic research initiative throughout NIH should focus on predisease pathways. Such an initiative would, of necessity, emphasize the unfolding interactions between environmental influences and gene expression over time. It should include the following topics:
identification of early markers of predisease states;
examination of their genetic and environmental origins through animal and human studies;
identification of behavioral risk factors in the exacerbation or amelioration of predisease pathways;
prioritization of experimental and longitudinal research to chart these trajectories across the life span;
focus on the mechanisms by which genetic influences, early life experiences, and behavioral and psychosocial risk factors across the life span interact, leading to accumulating physiological risk for a broad range of disease outcomes.
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