Aspects of Iron Metabolism Correlate with Epigenetic Age Acceleration
The consensus on iron is that higher levels become an issue in the context of aging, contributing to a number of issues such as raised oxidative stress and creation of the metabolic waste known as lipofuscin. Researchers here provide evidence for increased iron levels to correlate with epigenetic age acceleration, a measure of biological age. This is an expected result, given all of the other data on the possible role of dysfunctional iron metabolism in degenerative aging.
Iron is one of the most essential transition metals in the human body. The balance of iron metabolism, also known as iron homeostasis, is strictly regulated due to its crucial role in erythropoiesis, oxidative phosphorylation, and redox reaction. Evidence has connected altered iron homeostasis with biological aging. For example, epidemiological research reported that over 10% of both men and women aged 65 years or older were anemic in the US, in which iron deficiency made up approximately 20% of all anemia cases. Chronic inflammation of the elder people might also contribute to the alteration of serum iron biomarkers, causing iron deficiency and impaired iron mobilization. On the other hand, cellular iron accumulation in older individuals was observed. Serum level of ferritin, which reflected the storage of iron, was reported to be increasing with age and negatively associated with telomere length. Iron overload in cell induced the accumulation of lipofuscin, which was considered one of the hallmarks of aging and could be cytotoxic.
Epigenetic clocks based on DNA methylation status and chronological age and health-related outcomes were built to discover the impact of both genetic and environmental factors on human aging. Epigenetic age acceleration (EAA) was used to describe individuals with greater epigenetic-clock-estimated age than their true chronological age, indicating worse health outcome. Although iron homeostasis is connected with aging, no research regarding the relationship between epigenetic clocks or EAA and iron homeostasis has been conducted.
Utilizing outcomes from genome-wide association studies (GWAS), Mendelian randomization (MR) has been widely used in discovering causality between exposure factors and outcomes. Researchers have conducted a GWAS of four epigenetic clocks, and subsequent MR analysis identified several risk factors of EAAs. In this study, we conducted a two-sample MR analyses with summarized GWAS data mentioned above to investigate the causal relationship between iron homeostasis and EAAs. Each standard deviation (SD) increase in genetically predicted serum iron was associated with increased GrimAge acceleration (GrimAA), HannumAge acceleration (HannumAA), and Intrinsic epigenetic age acceleration (IEAA). Similar results were also observed in transferrin saturation. Transferrin carries and transports most of the serum iron to organs and tissues.
In conclusion, the results of the present investigation unveiled the causality of iron overload on acceleration of epigenetic clocks. Researches are warranted to illuminate the underlying mechanisms and formulate strategies for potential interventions.
So old people are literally and figuratively feeling a little rusty?
Dr Ester, in his book "The Mindspan Diet" proposes, with evidence and solutions, that the higher iron levels in Western diets compared with Japan, and a major source of the West's ageing mental problems .