Epigenetics as a Driver of Developmental Origins of Health and Disease: Did We Forget the Fathers?

What are the effects of our environment on human development and the next generation? Numerous studies have provided ample evidence that a healthy environment and lifestyle of the mother is important for her offspring. Biological mechanisms underlying these environmental influences have been proposed to involve alterations in the epigenome. Is there enough evidence to suggest a similar contribution from the part of the father? Animal models provide proof of a transgenerational epigenetic effect through the paternal germ line, but can this be translated to humans? To date, literature on fathers is scarce. Human studies do not always incorporate appropriate tools to evaluate paternal influences or epigenetic effects. In reviewing the literature, I stress the need to explore and recognize paternal contributions to offspring's health within the Developmental Origins of Health and Disease hypothesis, and coin this new concept the Paternal Origins of Health and Disease paradigm (POHaD). A better understanding of preconceptional origins of disease through the totality of paternal exposures, or the paternal exposome, will provide evidence‐based public health recommendations for future fathers.

     

Detection and analysis of endogenous polar volatile organic compounds (PVOCs) in urine for human exposome research

Background: The human exposome, defined as ‘…everything that is not the genome’, comprises all chemicals in the body interacting with life processes. The exposome drives genes x environment (GxE) interactions that can cause long-term latency and chronic diseases. The exposome constantly changes in response to external exposures and internal metabolism. Different types of compounds are found in different biological media.

Objective: Measure polar volatile organic compounds (PVOCs) excreted in urine to document endogenous metabolites and exogenous compounds from environmental exposures.

Methods: Use headspace collection and sorbent tube thermal desorption coupled with bench-top gas chromatography-mass spectrometry (GC-MS) for targeted and non-targeted approaches. Identify and categorize PVOCs that may distinguish among healthy and affected individuals.

Results: Method is successfully demonstrated to tabulate a series of 28 PVOCs detected in human urine across 120 samples from 28 human subjects. Median concentrations range from below detect to 165?ng/mL. Certain PVOCs have potential health implications.

Conclusions: Headspace collection with sorbent tubes is an effective method for documenting PVOCs in urine that are otherwise difficult to measure. This methodology can provide probative information regarding biochemical processes and adverse outcome pathways (AOPs) for toxicity testing.     

Biomarkers intersect with the exposome

The exposome concept promotes use of omic tools for discovering biomarkers of exposure and biomarkers of disease in studies of diseased and healthy populations. A two-stage scheme is presented for profiling omic features in serum to discover molecular biomarkers and then for applying these biomarkers in follow-up studies. The initial component, referred to as an exposome-wide-association study (EWAS), employs metabolomics and proteomics to interrogate the serum exposome and, ultimately, to identify, validate and differentiate biomarkers of exposure and biomarkers of disease. Follow-up studies employ knowledge-driven designs to explore disease causality, prevention, diagnosis, prognosis and treatment.     

The endogenous exposome

The concept of the Exposome is a compilation of diseases and one's lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the endogenous exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions.     

Susceptibility to COVID‐19 in populations with health disparities: Posited involvement of mitochondrial disorder,socioeconomic stress,and pollutants

SARS‐CoV‐2 is a novel betacoronavirus that has caused the global health crisis known as COVID‐19. The implications of mitochondrial dysfunction with COVID‐19 are discussed as well as deregulated mitochondria and inter‐organelle functions as a posited comorbidity enhancing detrimental outcomes. Many environmental chemicals (ECs) and endocrine‐disrupting chemicals can do damage to mitochondria and cause mitochondrial dysfunction. During infection, SARS‐CoV‐2 via its binding target ACE2 and TMPRSS2 can disrupt mitochondrial function. Viral genomic RNA and structural proteins may also affect the normal function of the mitochondria‐endoplasmic reticulum‐Golgi apparatus. Drugs considered for treatment of COVID‐19 should consider effects on organelles including mitochondria functions. Mitochondrial self‐balance and clearance via mitophagy are important in SARS‐CoV‐2 infection, which indicate monitoring and protection of mitochondria against SARS‐CoV‐2 are important. Mitochondrial metabolomic analysis may provide new indicators of COVID‐19 prognosis. A better understanding of the role of mitochondria during SARS‐CoV‐2 infection may help to improve intervention therapies and better protect mitochondrial disease patients from pathogens as well as people living with poor nutrition and elevated levels of socioeconomic stress and ECs.     

Geroscience and climate science: Oppositional or complementary?

Two of this century's most significant public health challenges are climate change and healthy aging. The future of humanity will be both warmer and older than it is today. Is it socially responsible, in a warming planet of a population exceeding 8 billion people, for science to aspire to develop gerotherapeutic drugs that aim to reduce the burden of aging-related diseases that may also increase lifespan? This question is the “elephant in the room” for geroscience advocacy. Science communication concerning what constitutes empirically valid and morally defensible ways of navigating the dual public health predicaments of climate change and healthy aging must be sensitive to both the interdependence of the environment (including planetary health) and the mechanisms of aging, as well as the common (mis)perceptions about the potential conflict between the goals of climate science and geroscience. Geroscience advocacy can transcend narratives of intergenerational conflict by highlighting the shared aspirations of climate science and geroscience, such as the goals of promoting health across the lifespan, redressing health disparities, and improving the economic prospects of current and future generations.