Biological aging measures demonstrate that iron overload makes you older. I do not know any other safe iron chelator than ATH434, at least I believe ATH434 is safe but still waiting for ph 2 results. This study demonstrates causality not only association. One day ATH needs to demonstrate that ATHE434 will decelerate biological aging. The first results in this respect are the both ph 2 studies.

Clin Epigenetics

. 2023 Oct 7;15(1):159.

doi: 10.1186/s13148-023-01575-w.

Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study

Zhihao Wang ^{# 1}, Yi Liu ^{# 2}, Shuxin Zhang ³, Yunbo Yuan ¹, Siliang Chen ¹, Wenhao Li ¹, Mingrong Zuo ¹, Yufan Xiang ¹, Tengfei Li ¹, Wanchun Yang ¹, Yuan Yang ¹, Yanhui Liu ⁴

Affiliations expand

• PMID: 37805541

DOI: 10.1186/s13148-023-01575-w

Abstract

Background: Epigenetic clocks constructed from DNA methylation patterns have emerged as excellent predictors of aging and aging-related health outcomes. Iron, a crucial element, is meticulously regulated within organisms, a phenomenon referred as iron homeostasis. Previous researches have demonstrated the sophisticated connection between aging and iron homeostasis. However, their causal relationship remains relatively unexplored.

Results: Through two-sample Mendelian randomization (MR) utilizing the random effect inverse variance weighted (IVW) method, each standard deviation (SD) increase in serum iron was associated with increased GrimAge acceleration (GrimAA, Beta_IVW = 0.27, P = 8.54E-03 in 2014 datasets; Beta_IVW = 0.31, P = 1.25E-02 in 2021 datasets), HannumAge acceleration (HannumAA, Beta_IVW = 0.32, P = 4.50E-03 in 2014 datasets; Beta_IVW = 0.32, P = 8.03E-03 in 2021 datasets) and Intrinsic epigenetic age acceleration (IEAA, Beta_IVW = 0.34, P = 5.33E-04 in 2014 datasets; Beta_IVW = 0.49, P = 9.94E-04 in 2021 datasets). Similar results were also observed in transferrin saturation. While transferrin manifested a negative association with epigenetic age accelerations (EAAs) sensitivity analyses. Besides, lack of solid evidence to support a causal relationship from EAAs to iron-related biomarkers.

Conclusions: The results of 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.