Manipulating the exposome to enable better ageing

Abstract

The sum total of life course exposures creates an exposome that has a significant impact on age-related health. Understanding the interplay between exposome factors and the (epi) genome, offers pertinent insights into the ageing process and its relationship with the accumulation of allostatic load. We propose to exploit this to develop a biomimetic approach that will provide insight into how evolution through natural selection in other species has solved many age related human health issues. In particular, we will emphasise the need to reconnect a more mechanistic approach to medical science with a broader natural sciences approach, using biomimetics to mitigate the global burden of age related ill health. In particular, we will discuss how such an approach indicates leverage of the activities of the Nrf 2 gene to enhance health span via reintroduction of the classical ‘Food as Medicine’ concept, including modulation of the microbiome and the creation of more salutogenic and biophilic environments. Additionally, we will discuss how this approach integrates with novel and developing senotherapies.

Cellular senescence: the good, the bad and the unknown

“…Cumulative lifetime exposure to external stressors, such as temperature, oxygen levels and inadequate nutrition, elicit adaptive homeostatic mechanisms, including antioxidant and anti-inflammatory responses, by activating the NRF2–KEAP1 signalling pathway 274 . Modifying these exposures might offer new strategies for improving the health span and combatting CKD and could potentially have beneficial effects on cellular senescence.…”

Cinnamon: an aromatic condiment applicable to chronic kidney disease

“…Studies on cinnamon in vitro, in animals, and in humans are listed in Table 5 [9,45,[131][132][133][134][135][136][137][138][139][140][141][142][143][144]. Again, allowance for different exposome features, such as microbiota composition, may be pertinent here [145].…”

Integrating Environment and Aging Research: Opportunities for Synergy and Acceleration

“…Evidence from toxicology, comparative biology, and epidemiology demonstrate an association between environmental toxicant exposures and numerous age-related outcomes. Much of what we know about biological susceptibility to environmental toxicant exposure comes from children’s environmental health and is now being applied to other susceptible populations like the aged population ( Craven et al, 2021 ; Shiels et al, 2021 ). Exposure and response relationships can vary based on acute, short term or long-term exposures and are dependent on the chemical structure and physiological properties of toxicants.…”

“…Diet quality is not only an important modifier of physiology, including gut microbiome composition which may affect detoxification. Diet is also often a source of toxicant exposure ( Roy et al, 2003 ; Wang et al, 2019 ) and has been shown to alter circadian rhythm homeostasis ( Gundert-Remy et al, 2015 ; Craven et al, 2021 ; Shiels et al, 2021 ). Diet is often linked with other lifestyle, behavioral or social factors that contribute to increased vulnerability to multiple sources of toxicants and social stressors simultaneously.…”