The Chemical Exposome of Human Aging

Abstract

Aging is an inevitable biological phenomenon displayed by single cells and organs to entire organismal systems. Aging as a biological process is characterized as a progressive decline in intrinsic biological function. Understanding the causative mechanisms of aging has always captured the imagination of researchers since time immemorial. Although both biological and chronological aging are well defined and studied in terms of genetic, epigenetic, and lifestyle predispositions, the hallmarks of aging in terms of small molecules (i.e., endogenous metabolites to chemical exposures) are limited to obscure. On top of the endogenous metabolites leading to the onset and progression of healthy aging, human beings are constantly exposed to a natural and anthropogenic "chemical" environment round the clock, from conception till death, affecting one's physiology, health and well-being, and disease predisposition. The research community has started gaining sizeable insights into deciphering the aging factors such as immunosenescence, nutrition, frailty, inflamm-aging, and diseases till date, without much input from their interaction with exogenous chemical exposures. The "exposome" around us, mostly, accelerates the process of aging by affecting the internal biological pathways and signaling mechanisms that result in the deterioration of human health. However, the entirety of exposome on human aging is far from established. This review intends to catalog the known and established associations of the exposome from past studies focusing on aging in humans and other model organisms. Further discussed are the current technologies and informatics tools that enable the study of aging exposotypes, and thus, provide a window of opportunities and challenges to study the "aging exposome" in granular details.

Keywords: aging; exposome; informatics; mass spectrometry; metabolite; model; pollution; telomere.

FIGURE 1

(A) Growth in research publications at PubMed pertaining to “exposomics” and “exposomics and aging” research. (B) Human aging from child birth (neonatal) through adolescence and the ultimate of life, death are riddled with exposure to chemicals surrounding us. As with the incremental aging one experiences physiological decline, possibly the cumulative exposome increases inside human body. (C) Human chemical exposure ranges from addiction (alcohol, drugs, cocaine, and smoking), to air pollution (PM, gases, industrial vapors), water (pollutions, pesticides, and PFAS), drugs (pharmaceuticals, and medications), the resident internal and external gut microbiome, domestic waste and indoor pollution (dust, cooking, and gases), occupational exposures (hospital disinfectants to asbestosis), pollution (fossil fuel burning to plastic), pets (carrying environmental pollution to microbiome), personal hygiene products (PHPs) (perfumes to soaps) to diet (and nutrition).

FIGURE 2

Range of human chemical exposures that are associated with aging. From heavy metals/ions to particulate matter (PM) of various sizes (PM_2.5, PM₁₀), carbon black (BC), pesticides, PDBEs, phthalates, BPA, drugs (methamphetamine, paracetamol) to metalloids (methylmercury, arsenate) to chemicals from addiction (ethanol, nicotine, cocaine). Shown also are selenium and crocin (from Saffron plant) that exert protective effect on aging.

FIGURE 3

Mass spectrometry and spectroscopy provide the necessary analytical tools that aid in capturing the aging “exposome,” which when processed by the software tools, resources, and databases enable to “crack” (identify) the known and unknown chemical exposome.