TABLE 2.
List of studies that looked at exposure and its effect on aging in animal models.
| Exposure | Models | Treatment | Findings | Link |
| Fatty acid hydroperoxides (OFA) and/or vit E | Porcine cells | Exposure to 5 μM OFA for 40 passages | Age-related decrease in endothelial barrier function (EBF), while supplementation of OFA-treated cultures with 25 μM vit E protected against the OFA-mediated decrease in EBF, chronic oxidative stress decreased EBF, predisposing the artery to infiltration by blood components and subsequent atherogenesis. | Boissonneault et al., 1990 |
| Bisphenol A (BPA) | C. elegans | Does of 0, 100, 500, and 1,000 μM of BPA, and 0, 10, 25, and 50 μM of BPA | Increased the generation of hydrogen peroxide-related ROS and superoxide anions, accelerated aging by the induction of oxidative stress. | Tan et al., 2015 |
| Arsenite | C. elegans | Arsenite exposure (100 μM) | Age biomarkers affected: a decrease of defecation frequency, accumulations of intestinal lipofuscin and lipid peroxidation in an age-dependent manner; increased intracellular ROS level; increased mRNA levels of transcriptional makers of aging (hsp-16.1, hsp-16.49, and hsp-70); chronic arsenite exposure resulted in accelerated aging process. | Yu et al., 2016 |
| Arsenite | C. elegans | Exposure to 0.1–1,000 μM arsenite | Transient increase in ROS levels in, co-exposure to ROS scavengers prevented the lifespan-extending capabilities of arsenite (i.e., mitohormesis), low-dose arsenite extended lifespan, providing evidence for nonlinear dose-response characteristics of toxin-mediated stress resistance and longevity. | Schmeisser et al., 2013 |
| Cocaine, nicotine | Rattus norvegicus | High-dose cocaine (40 mg/kg/d), or, high-dose nicotine (5.0 mg/kg/d) | Prenatal exposure showed long-term effects on emotional behavior. Combinations led to depressive symptoms, in a dose-dependent manner. | Sobrian et al., 2003 |
| Alcohol | Rattus norvegicus | Liquid alcohol diets containing 0, 17.5, or 35% ethanol-derived calories, from gestation d 7 to parturition | Showed a peripheral auditory disorder in the form of congenital sensorineural hearing loss; punctate lesions and malformed stereocilia on the auditory sensory receptor cells of the inner ear; central auditory processing disorder characterized by prolonged transmission of neural potentials along the brainstem portion of the auditory pathway; age-related deterioration of auditory acuity. | Church et al., 1996 |
| Endocrine disruptors | Rattus norvegicus | Twelve consecutive d of vehicle (dimethylsulfoxide), estradiol benzoate (EB) (1 mg/kg), and MXC (methoxychlor) (low dose, 20 μg/kg or high dose, 100 mg/kg), beginning on embryonic d 19 through post-natal d 7 | Early life exposure has lifelong effects on neuroendocrine gene expression and DNA methylation, caused advancement of reproductive senescence | Gore et al., 2011 |
| Endocrine disrupting chemicals (EDCs) | Rattus norvegicus | Mixture of phthalates, pesticides, UV-filters, bisphenol A, butylparaben, paracetamol | In pre-pubertal rats, a significant reduction in primordial follicle numbers, reduced plasma levels of prolactin; incidence of irregular estrous cycles was higher, reduced ovary weights, raises concern regarding potential effects of mixtures of EDCs on female reproductive function. | Johansson et al., 2016 |
| Estradiol benzoate (EB) | Rattus norvegicus | Silastic implants containing estradiol benzoate (EB) in solution placed into 5 d old female Wistar rats and removed 1 or 5 d later | Premature occurrence of vaginal opening was observed in all three estrogenized groups independently of EB; ovaries of these last two groups showed a reduced number of corpora lutea and an increased number of large follicles, ovarian weight and progesterone content gradually. | Rodriguez et al., 1993 |
| Methylmercury | Rattus norvegicus | Pregnant females exposed to drinking water containing 0, 0.5, or 6.4 ppm Hg as methylmercury, i.e., 40 and 500 μg/kg/d of mercury intake | Prenatal exposure retarded the acquisition of choice in older rats, yet, two rate measures, lever-press rates and changeover rates, were not systematically affected by methylmercury. | Newland, 2004 |
| Methylmercury | Rattus norvegicus | Doses of 0, 0.5, or 6.4 ppm Hg in the drinking water of female rats at least 4 weeks before mating and continuing until post-natal 16 d | Gradual decline in the reinforcement rate began to appear in low- and high-dose rats at about 500 and 800 d of age, respectively, the lever-press duration increased, the inter-response time (IRT) was unaffected, and the time between response bursts increased. | Newland and Rasmussen, 2000 |
| Triethyltin (TET) | Rattus norvegicus | Dosed with TET (5 mg/kg) | At 24 months, TET-treated rats showed significant deficits in acquisition and retention of the water maze task; resulted in morphological damage that was apparent behaviourally. | Barone et al., 1995 |
| Aluminum | Rattus norvegicus | Pregnant females orally exposed to 0, 50, and 100 mg Al/kg/d | Decreased learning performance of the task in both adult and old rats, age-related effect on water maze performance, accumulation of Al in brain at 2 years of age. | Roig et al., 2006 |
| 5-bromo-2’-deoxyuridine | Rattus norvegicus | Subcutaneous injections (3.2 mg) of a synthetic analog of thymidine, 5-bromo-2’-deoxyuridine (BrdUrd), on 1 and 3 d, or 1, 3, 7, and 21 d of post-natal life | Mean life span decreased by 31 and 38% in male and by 14 and 27% in female rats that received 2 and 4 injections of BrdUrd; opening of the vagina was delayed, inhibition of compensatory ovarian hypertrophy induced by hemiovariectomy at the age of 3 months was found in females; neonatal administration of BrdUrd to rats doubles the incidence of chromosome aberrations in peripheral blood lymphocytes; dose-related increase in tumor incidence. | Anisimov and Osipova, 1992 |
| Di(2-Ethylhexyl) Phthalate | Mus musculus | Orally dosed DEHP (20μg/kg/d−500 mg/kg/d) daily for 10 d | DEHP significantly decreased inhibin B levels; significantly increased the BAX/BCL2 ratio in primordial follicles leading to a significant decrease in primordial and total follicle numbers | Hannon et al., 2016 |
| DecaBDE Polybrominated diphenyl ethers (PBDEs) | Mus musculus | Daily oral dose of 0, 6, or 20 mg/kg decaBDE from post-natal 2–15 d | Performance of the aging cohort was significantly affected, on the light–dark discrimination, older decaDBE treated mice learned the task more slowly, made more perseverative errors after an initial error, and had lower latencies to respond compared with controls. | Rice et al., 2009 |
| Alcohol | Mus musculus | Single teratogenic dose (5.8 g/kg) of ethyl alcohol during organogenesis on the 9th d of gestation | In adulthood, the offspring suffered a deficit in long-term retention, but not acquisition, of a place learning task; the retention deficit was severe in aging mice. | Dumas and Rabe, 1994 |
| Lead | Mus musculus | Pb/E exposure, 0.2% Pb-acetate added to the deionized drinking water of the pregnant female | Up-regulation of genes related to the immune response, metal-binding, metabolism and transcription/transduction coupling; disturbances in developmental stages of the brain compromise the ability to defend against age-related stressors. | Dosunmu et al., 2012 |