(P22-023-25) The Impact of Low Dietary Level Cadmium Exposure on Aging Phenotypes

Objectives: Cadmium (Cd), a toxic environmental metal, accumulates in the body through dietary, environmental, and occupational sources, with a notably long biological half-life. Cd exposure induces oxidative damage to lipids, proteins, and DNA, which is a well-established hallmark of aging. Cd is a neurotoxin associated with cognitive impairment and neurodegenerative diseases such as Alzheimer’s disease. While high-dose Cd toxicity is well studied, the impacts of chronic low-dose exposure on the aging process remain unclear. Therefore, in the present study, we examined the impacts of low-level Cd exposure on aging using an aged mouse model.

Methods: Male C57BL/6J mice, aged 18–20 months, were provided ad libitum access to a standard diet (13% kcal from fat) and water, either containing or free of 3.3 mg Cd/L, for 12 weeks. Cognitive function was evaluated using the Y-maze test, while muscle function was assessed through a grip strength test. Oxidative stress was assessed by analyzing the redox states of thiol/disulfide redox couples using high-performance liquid chromatography (HPLC), while Cd levels in brain tissues were quantified using inductively coupled plasma mass spectrometry (ICP-MS).

Results: In male mice, Cd treatment significantly impaired cognitive function compared to the control group (Control: 66.7 ± 2.2%; Cd: 49.2 ± 4.0%; p < 0.001). Cd levels in brain tissue, quantified by ICP-MS, were higher in the Cd-treated group (1.0 ng/g tissue) than the control group(0.49 ng/g tissue). There were no observable differences between Cd-treated and control groups in measures of grip strength, body weight, and white adipose tissue mass. HPLC analysis showed that Cd treatment significantly increased the oxidation of redox states in glutathione (E_hGSSG: Control: -265.8 ± 3.8 mV; Cd: -246.7 ± 4.1 mV; p < 0.05) and cysteine (E_hCySS: Control: -145.4 ± 10.3 mV; Cd: -97.0 ± 3.7 mV; p < 0.001) in liver tissues. Consistently, systemic oxidative stress was observed, with Cd treatment causing a significant increase in plasma E_hGSSG (Control: -157.7 ± 6.8 mV; Cd: -98.7 ± 15.8 mV; p < 0.001).

Conclusions: Our data show that Cd deposition from low-level dietary Cd exposures exacerbates aging phenotypes, including cognitive impairment and increased oxidative stress.

Funding Sources: NIA grant R21 AG080247, and NIEHS grants R01 ES031980 and P30 ES019776.