Mobile Menu

Hallmarks of environmental insults

We summarise a recent paper, published in Cell, that has proposed eight hallmarks of environmental insults.

The intricacies and interactions between our genetics and the environment play a critical role in our health and also in disease. Environmental exposures impact us throughout our entire lives – from conception to death. They influence gene expression, shape the immune system, trigger many physiological responses and also determine wellbeing and disease.

Contaminated air, water, soil, food and occupational and household settings are continually exposing humans of all ages to a plethora of chemicals and environmental stressors. As the proportion of older individuals is increasing, environmental exposures are contributing more to the modifiable risk factors that underpin ageing and chronic disease.

The hallmarks of environmental insults

Below we summarise that eight proposed hallmarks of environmental insults that describe both the cellular and molecular processes involved in linking environmental exposures to chronic diseases.

Oxidative stress and inflammation

Our ability to respond to oxidative stress is a central determinant of ageing and longevity. It is also implicated in many diseases, including cancer, atherosclerosis, cardiovascular diseases, respiratory diseases and neurological diseases. Many environmental exposures can induce oxidative stress which results in inflammation.

Genomic alterations and mutation

Somatic mutations accumulate with age. They are associated with a variety of diseases. Mutagenesis studies have long identified a host of environmental chemicals that are mutagens, which contribute to mutational burden and support the link between environmental exposures and chronic disease development.

Epigenetic alterations

Studies have shown that environmental exposures cause alterations in gene regulation through alterations in DNA methylation and histone modifications. This promotes ageing-related epigenetic changes, including the acceleration of epigenetic clocks.

Mitochondrial dysfunction

Mitochondrial dysfunction is involved in many chronic diseases and ageing. It has been shown that environmental exposures can induce alterations in mtDNA content, nucleus-mitochondria cross talk and also mitochondrial epigenetics. Recent evidence has also highlighted that environmental exposures jointly affect the telomere-mitochondrial ageing axis.

Endocrine disruption

Endocrine disrupting chemicals are found in our environment, food and consumer products. Alterations of the endocrine system are responsible for many physiological changes during development and normal ageing as well as in chronic diseases.

Altered intercellular communication

Intracellular communications are key to biological ageing. Environmental exposures can specifically activate and/or disrupt intracellular communications. For example, increasing evidence is showing that senescence-associated secretory phenotype (SASP) is affected by environmental exposures.

Altered microbiome communities

The microbiome is an emerging key player in ageing and longevity. The microbiome of the barrier organs, in particular, are linked to communities of microorganisms from the environment. Misbalance of the microbiome and reduced diversity play important roles in the development of chronic diseases. Environmental insults induce these imbalances but can also protect against allergies and significantly contribute to barrier organ functioning. 

Impaired nervous system function

Environmental exposures, such as noise, heat and light, can directly modulate and impair the nervous system via sensory organs. They can induce stress responses and a number of downstream responses. Brain development and neurodegenerative diseases are significantly impacted by neurotoxic chemicals.


Environmental insults are universal and highly complex. They impair essential cellular function and lead to a plethora of diseases. These eight hallmarks underpin most observed associations between environmental exposures and disease. They also provide a framework for understanding how environmental insults can lead from health to manifestation of disease. In addition, they call for novel experimental research to expand our knowledge of disease mechanisms beyond genetics.

Image credit: By jcomp – freepik