Summary: Elevated iron levels in the blood appear to accelerate biological aging. Monitoring and managing iron levels may help reduce age-related health decline and lower the risk of neurodegenerative disease.
Source: University of Edinburgh
Researchers have identified genetic regions associated with aging that may help explain why people age at different rates.
An international team analysed genetic data from very large public datasets and found links between genes that influence iron metabolism and measures of biological aging. Their work suggests that maintaining healthy blood iron levels could be an important factor in preserving health during aging and extending disease-free years of life.
The study combined genome-wide association summary statistics for three related aging outcomes—lifespan, healthspan (years lived free of major disease), and exceptional longevity—and used a multivariate approach to increase statistical power. By pooling data across multiple resources, the researchers achieved an analysis equivalent to observing approximately 1.75 million lifespans and more than 60,000 extremely long-lived individuals, allowing them to detect genetic signals that smaller studies may have missed.
The team pinpointed ten genomic regions associated with all three ageing measures and implicated 78 genes overall. Several of these regions overlap with genes already known to be involved in age-related cardiovascular conditions, while others represent novel candidates for follow-up studies. Notably, five loci near FOXO3, SLC4A7, LINC02513, ZW10, and FGD6 reached genome-wide significance for the first time in this analysis.
Pathway analysis showed enrichment for biological processes previously implicated in ageing across model organisms, including DNA damage response, apoptosis, and physiological homeostasis. A particular pathway highlighted by the authors for further investigation is haem (iron-containing molecule) metabolism, which connects directly to the study’s signal implicating iron biology in human aging.
To test whether the relationship between iron-related genes and longevity is likely to be causal, the researchers applied Mendelian randomisation, a statistical technique that uses genetic variants as natural experiments to strengthen causal inference. Results from these analyses supported a role for genes involved in iron metabolism influencing healthy ageing and lifespan.
Blood iron levels are shaped by diet, genetics, and physiology. Both iron deficiency and iron overload have been associated with adverse health outcomes, and iron-rich diets—particularly those high in red meat—have previously been linked to higher risk of some age-related diseases. The current genetic findings provide complementary evidence that iron regulation may be an important lever for health during ageing.
The authors propose that drugs designed to mimic protective genetic variation in iron handling could, in future, be investigated as a way to reduce age-related damage and extend the healthy years of life. They also emphasise that further laboratory and clinical research will be necessary to translate genetic insights into safe, effective interventions.
Anonymised genetic summary data for healthspan, lifespan, and longevity used in this analysis were obtained from publicly available repositories, allowing the team to undertake a large-scale multivariate genomic scan. The study was supported by funding from the Medical Research Council and is published in the journal Nature Communications.
Dr Paul Timmers of the Usher Institute at the University of Edinburgh commented: “We are very excited by these findings as they strongly suggest that high levels of iron in the blood reduce our healthy years of life, and keeping these levels in check could prevent age-related damage. We speculate that our findings on iron metabolism might also start to explain why very high levels of iron-rich red meat in the diet have been linked to age-related conditions such as heart disease.”
Dr Joris Deelen of the Max Planck Institute for Biology of Ageing added: “Our ultimate aim is to discover how aging is regulated and find ways to increase health during aging. The ten regions of the genome we have discovered that are linked to lifespan, healthspan and longevity are all exciting candidates for further studies.”
About this aging research article
Source:
University of Edinburgh
Media Contacts:
Kate McAllister – University of Edinburgh
Image Source:
The image is in the public domain.
Original Research: Open access
“Multivariate genomic scan implicates novel loci and haem metabolism in human ageing”. Paul R. H. J. Timmers, James F. Wilson, Peter K. Joshi & Joris Deelen. Nature Communications.
Abstract
Minor neuropsychological deficits in patients with subjective cognitive decline
Ageing phenotypes—such as years lived in good health (healthspan), total years lived (lifespan), and survival to exceptional old age (longevity)—are of wide scientific and public interest but demand very large sample sizes to study genetically. By combining existing genome-wide association summary statistics for healthspan, parental lifespan, and longevity into a single multivariate framework, the authors increased statistical power and identified ten genomic loci that influence all three phenotypes. Five of these loci (near FOXO3, SLC4A7, LINC02513, ZW10, and FGD6) are newly reported at genome-wide significance. Many of the identified regions are associated with cardiovascular disease and affect genes whose expression changes with age. Overall, 78 genes were implicated and found to be enriched for ageing-related pathways highlighted in model organisms—including the response to DNA damage, programmed cell death, and physiological homeostasis—and the study highlights haem metabolism as a pathway meriting further investigation.