The impact of prenatal and early-life arsenic exposure on epigenetic age acceleration among adults in Northern Chile

Abstract

Background Exposure to arsenic affects millions of people globally. Changes in the epigenome may be involved in pathways linking arsenic to health or serve as biomarkers of exposure. This study investigated associations between prenatal and early-life arsenic exposure and epigenetic age acceleration (EAA) in adults, a biomarker of morbidity and mortality. Methods DNA methylation was measured in PBMCs and buccal cells from 40 adults (median age = 49 years) in Chile with and without high prenatal and early-life arsenic exposure. EAA was calculated using the Horvath, Hannum, PhenoAge, skin and blood, GrimAge, and DNAm telomere length clocks. We evaluated associations between arsenic exposure and EAA using robust linear models. Results Participants classified as with and without arsenic exposure had a median drinking water arsenic concentration at birth of 555 and 2ug/L, respectively. In PBMCs, adjusting for sex and smoking, exposure was associated with a six-year PhenoAge acceleration in PBMCs [B (95% CI) = 6.01 (2.60, 9.42)]. After adjusting for cell type composition, we found positive associations with Hannum EAA [B (95% CI) = 3.11 (0.13, 6.10)], skin and blood EAA [B (95% CI) = 1.77 (0.51, 3.03)], and extrinsic EAA [B (95% CI) = 4.90 (1.22, 8.57)]. The association with PhenoAge acceleration in buccal cells was positive but not statistically significant [B (95% CI) = 4.88 (-1.60, 11.36)]. Conclusions Arsenic exposure limited to early-life stages may be associated with biological aging in adulthood. Future research may provide information on how EAA programmed in early-life is related to health.

Associations of prenatal one-carbon metabolism nutrients and metals with epigenetic aging biomarkers at birth and in childhood in a US cohort

“…Prenatal As concentrations were associated with greater Bohlin EGAA at birth ( B (95% CI) = 0.09 weeks (0.01, 0.16)) and Horvath EAA in mid-childhood ( B (95% CI) = 0.30 years (0.14, 0.46)) after adjusting for maternal fish consumption. Blood As concentrations have also been associated with Horvath EAA in cross-sectional analyses in older adults [ 55 ], and prenatal and early-life As exposure has been associated with Hannum, PhenoAge, and extrinsic EAA among adults in Northern Chile [ 63 ]. Our findings that prenatal As levels affect biomarkers associated with mortality and mortality later in life reflect existing evidence that As exposure during crucial developmental periods increases the risk of cancers and chronic diseases.…”

Testicular histone hyperacetylation in mice by valproic acid administration affects the next generation by changes in sperm DNA methylation

“…VPA and saline were administered daily via intraperitoneal injection to mice for 4 weeks from 6 to 10 weeks of age. The timing of this administration was determined based on the chemical effects that occurred before sexual maturity and epigenomic effects after maturity [23,24]. Two weeks after the final dose, 38 animals were sacrificed at 12 weeks of age and used for in vitro fertilization and sperm DNA methylation analysis.…”

Exploring the Interplay between Arsenic and Cutaneous Physiology, Pathology, and Regeneration

“…Organ pathophysiology is directly correlated with age, and oxidative stress negatively impacts the body and worsens with age [98]. There is a correlation between epigenetic age acceleration and prenatal and early-life arsenic exposure [99]. The balance between adipogenic and osteogenic differentiation may be impacted by arsenic exposure's promoting senescence in human mesenchymal stem cells.…”