The Food and Drink Environmental Exposome as a Driver of Biological Ageing and Age-related Diseases

Ageing is the progressive loss of physiological integrity and the primary risk factor for the major age-related pathologies. Twelve hallmarks have been defined as the mechanistic substrate through which it operates, and their accumulation defines biological age that may diverge from chronological age. Biological age is sensitive to environmental and lifestyle factors, among them chemical exposure. Here we review the evidence linking ten synthetic compounds, spanning five classes defined by how they reach food, to the hallmarks of ageing across three levels of evidence: cell models, animal models and human association studies. Structurally unrelated compounds converge on a small number of proximal events that lie upstream of several hallmarks, although the full mechanistic chain has been resolved for only two of them. Human population studies link exposure to several of these compounds to age-related neurological disorders, frailty and all-cause mortality. The principal limitations of this evidence base are uneven coverage across hallmarks, the absence of a continuous chain of evidence between the three levels, and experimental in vitro and in vivo concentrations that exceed measured human exposure by up to several orders of magnitude. Addressing these, through realistic doses and mixtures, ageing-relevant endpoints and broader hallmark coverage, would allow this evidence to inform regulatory assessment and population-level intervention.