Kelvin J. A. Davies

DNAmPhenoAge, DNAmGrimAge, and the newly developed DNAmFitAge are DNA methylation (DNAm)-based biomarkers that reflect the individual aging process. Here, we examine the relationship between physical fitness and DNAm-based biomarkers in adults aged 33–88 with a wide range of physical fitness (including athletes with long-term training history). Higher levels of VO2max (ρ = 0.2, p = 6.4E − 4, r = 0.19, p = 1.2E − 3), Jumpmax (p = 0.11, p = 5.5E − 2, r = 0.13, p = 2.8E − 2), Gripmax (ρ = 0.17, p = 3.5E − 3, r = 0.16, p = 5.6E − 3), and HDL levels (ρ = 0.18, p = 1.95E − 3, r = 0.19, p = 1.1E − 3) are associated with better verbal short-term memory. In addition, verbal short-term memory is associated with decelerated aging assessed with the new DNAm biomarker FitAgeAcceleration (ρ: − 0.18, p = 0.0017). DNAmFitAge can distinguish high-fitness …

As the COVID-19 pandemic intensified the global health crisis, the containment of SARS-CoV-2 infection in pregnancies, and the inherent risk of vertical transmission of virus from mother-to-fetus (or neonate) poses a major concern. Most COVID-19-Pregnancy patients showed mild to moderate COVID-19 pneumonia with no pregnancy loss and no congenital transmission of the virus; however, an increase in hypoxia-induced preterm deliveries was apparent. Also, the breastmilk of several mothers with COVID-19 tested negative for the virus. Taken together, the natural barrier function during pregnancy and postpartum seems to deter the SARS-CoV-2 transmission from mother-to-child. This clinical observation warrants to explore the maternal-fetal interface and identify the innate defense factors for prevention and control of COVID-19-Pregnancy. Lactoferrin (LF) is a potent antiviral iron-binding protein present in the …

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Multiple roles of reactive oxygen species (ROS) and their consequences for health and disease are emerging throughout biological sciences. This development has led researchers unfamiliar with the complexities of ROS and their reactions to employ commercial kits and probes to measure ROS and oxidative damage inappropriately, treating ROS (a generic abbreviation) as if it were a discrete molecular entity. Unfortunately, the application and interpretation of these measurements are fraught with challenges and limitations. This can lead to misleading claims entering the literature and impeding progress, despite a well-established body of knowledge on how best to assess individual ROS, their reactions, role as signalling molecules and the oxidative damage that they can cause. In this consensus statement we illuminate problems that can arise with many commonly used approaches for measurement of ROS and …

Coronavirus Disease 2019 (COVID-19) triggered by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has been declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Oxidative stress and its related metabolic syndromes are potential risk factors in the susceptibility to, and severity of COVID-19. In concert with the earliest reports of COVID-19, obstetricians started to diagnose and treat SARS-CoV-2 infections during pregnancy (“COVID-19-Pregnancy”). High metabolic demand to sustain normal fetal development increases the burden of oxidative stress in pregnancy. Intracellular redox changes intertwined with acute phase responses at the maternal-fetal interface could amplify during pregnancy. Interestingly, mother-to-fetus transmission of SARS-CoV-2 has not been detected in most of the COVID-19-Pregnancy cases. This relative absence of vertical …

The USC-Buck Nathan Shock Center of Excellence in the Biology of Aging is a new and fully integrated multi-institutional center focused on training the next generation of geroscientists and providing access to cutting-edge geroscience technologies to investigators across the nation. The USC-Buck NSC is devoted to forging a deeper understanding of how and why aging processes cause disease in order to advance the translation of basic research on aging into effective preventions and therapies. Including more than 61 NIA-supported investigators, six NIA-funded research centers, four NIA T32s, and several additional aging research centers of excellence, the USC-Buck NSC constitutes one of the largest collections of leaders in geroscience research within the USA; the unique nature of the USC-Buck NSC research infrastructure ensures an integrated organization that is representative of the wide …

Overall mental health depends in part on the blood-brain barrier, which regulates nutrient transfer in-and-out of the brain and its central nervous system. Lactoferrin, an innate metal-transport protein, synthesized in the substantia nigra, particularly in dopaminergic neurons and activated microglia is vital for brain physiology. Lactoferrin rapidly crosses the blood-brain barrier via receptor-mediated transcytosis and accumulates in the brain capillary endothelial cells. Lactoferrin receptors are additionally present on glioma cells, brain micro-vessels, and neurons. As a regulator of neuro-redox, microglial lactoferrin is critical for protection/repair of neurons and healthy brain function. Iron imbalance and oxidative stress are common among patients with neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, dementia, depression, and multiple sclerosis. As an endogenous iron-chelator, lactoferrin …

Both internal and external redox signals routinely modify patterns of gene expression via discrete signal transduction pathways. Several such signaling pathways are protective in nature. These include the Nuclear Respiratory Factor2 (NRF2) signaling pathway that can increase synthesis of the mitochondrial Lon protease via increased transcription and translation of the lon gene. The Lon protease maintains quality control of the mitochondrial proteome by eliminating damaged proteins, allowing replacement proteins to be synthesized. We have shown that normal levels of Lon maximize mitochondrial lifetime and minimize mitoptosis, whereas Lon down-regulation results in abnormal mitochondrial morphology and function and increased cell death.Biological systems continuously make short-term adaptations both to set-points, and to the range of “normal” capacity, due to mild conditional changes, or to subtoxic …