Analysis of epigenetic clocks links yoga, sleep, education, reduced meat intake, coffee, and a SOCS2 gene variant to slower epigenetic aging.

DNA methylation (DNAm) clocks hold promise for measuring biological age, useful for guiding clinical interventions and forensic identification. This study compared the commonly used DNAm clocks, using DNA methylation and SNP data generated from nearly 1000 human blood or buccal swab samples. We evaluated different preprocessing methods for age estimation, investigated the association of epigenetic age acceleration (EAA) with various lifestyle and sociodemographic factors, and undertook a series of novel genome-wide association analyses for different EAA measures to find associated genetic variants. Our results highlighted the Skin&Blood clock with ssNoob normalization as the most accurate predictor of chronological age. We provided novel evidence for an association between the practice of yoga and a reduction in the pace of aging (DunedinPACE). Increased sleep and physical activity were associated with lower mortality risk score (MRS) in our dataset. University degree, vegetable consumption, and coffee intake were associated with reduced levels of epigenetic aging, whereas smoking, higher BMI, meat consumption, and manual occupation correlated well with faster epigenetic aging, with FitAge, GrimAge, and DunedinPACE clocks showing the most robust associations. In addition, we found a novel association signal for SOCS2 rs73218878 (p = 2.87 × 10-8) and accelerated GrimAge. Our study emphasizes the importance of an optimized DNAm analysis workflow for accurate estimation of epigenetic age, which may influence downstream analyses. The results support the influence of genetic background on EAA. The associated SOCS2 is a member of the suppressor of cytokine signaling family known for its role in human longevity. The reported association between various risk factors and EAA has practical implications for the development of health programs to improve quality of life and reduce premature mortality associated with age-related diseases.

Thyroid diseases and second to fourth digit ratio in Polish adults.

The association between second to fourth finger ratio and thyroid diseases is unexplained. There is a possible interaction between prenatal exposition to sex hormone and thyroid functions in the adulthood. The study included 175 adults investigated in Lódz in the central Poland. It consisted of two main parts: a survey including questions about occurrence of thyroid gland dysfunction and anthropometric measurements (body mass and height and length of the second and fourth finger, waist and hip circumferences). The women who had thyroid disease had higher 2D:4D digit ratio (left hand) (mean = 1.004; SD = 0.036) than healthy ones (mean = 0.989; SD = 0.030) (t = - 2105; p = 0.038; d = 0.707). The association between thyroid diseases occurrence and prenatal steroid hormone exposition is noticed. Only females who had thyroid diseases tend to have higher 2D:4D digit ratio, for left hand.

N-acetylserotonin reduces lipopolysaccharide-induced lipid peroxidation in vitro more effectively than melatonin.

OBJECTIVE: Bacterial lipopolysaccharide (LPS) causes lipid peroxidation (LPO). We have found that LPS induces LPO in vitro, in tissue homogenates in a concentration-dependent manner, the concentration of 400 µg/ml demonstrating the most efficient lipid damaging effect . Both melatonin and its precursor, N-acetylserotonin, must possess antioxidant activities, both in vivo or in vitro, however, following some claims, N-acetylserotonin is a more effective extra- and intracellular antioxidant than melatonin. The aim of our study was to compare the effects of melatonin and N-acetylserotonin on the LPS-induced LPO in vitro. METHODS: Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) concentrations were measured as the indices of induced membrane peroxidative damage in brain, liver and kidney homogenates. Both melatonin and N-acetylserotonin were used at increasing concentrations, starting from 0.01-5 mM, together with LPS at one concentration level of 400 µg/ml. RESULTS: In all the examined tissues, LPS stimulated LPO, while both melatonin and N-acetylserotonin decreased LPS-stimulated LPO. Furthermore, the capacity of N-acetylserotonin reducing LPO was higher than that of melatonin. CONCLUSIONS: The results of the reported study clearly indicate that N-acetylserotonin is a much stronger antioxidant in vitro than melatonin in terms of reducing oxidative damage to lipid membranes. However, it remains still unclear how the features relate to in vivo circumstances.

Effects of certain antioxidants on lipid peroxidation process in lung homogenates of L thyroxine-receiving rats.

OBJECTIVE: A possible role of antioxidants in thyreotoxicosis was investigated. We examined the parameters of lipid peroxidation (LPO): conjugated dienes (CD), malondialdehyde (MDA), Schiff bases (SB) in lung homogenates of male Wistar rats. METHODS: Two control groups were created: Group 1 - intact animals and Group 2 - animals injected with 0,9% NaCl. In Experiment I, the animals received L-thyroxin (LT4) i.p. (Groups 3-7). After one week the rats received additionally: Group 4 - melatonin (MEL); Group 5 - propylthiouracil (PTU); Group 6 - Ambroxol (AMB); Group 7 - N-acetylocysteine (NAC). In Experiment II, the animals received only antioxidants. RESULTS: In Experiment I, we noticed a significantly higher MDA and SB level in Group 2, compared to that in Group 1. Moreover, we observed a significantly higher MDA and SB level in Group 3, vs. that in Group 1, but SB level was lower in Group 3 than in Group 2. Melatonin, PTU and NAC reduced CD; PTU, AMB diminished MDA and MEL, AMB lowered SB levels as compared to Group 3. In Experiment II, we observed significantly higher MDA and SB level in Group 2, vs. that in Group 1. Melatonin, AMB and NAC decreased MDA and SB level, when compared to Group 2 but PTU elevated MDA and SB level vs. that in Group 1. CONCLUSIONS: 1) L-T4 suppresses LPO, 2) MEL, AMB and NAC protect against LPO, 3) PTU is an antioxidant in thyreotoxicosis, however, when administered alone, it enhances LPO, 4) stress accelerate LPO.

Potassium iodide changes the levels of thyroid hormones in goitrogenic rats on selenium deficient diet.

OBJECTIVE: A possible link was proposed between selenium [Se(-)], iodine deficiency and thyroid pathology. The aim of the study was to examine changes in FT3 and FT4 concentrations, weights of the thyroid glands and ioduria after potassium iodide (KI) in normal and goitrogenic rats on Se(-) diet. METHODS: Wistar rats in Group 1 received the standard diet. Other animals remained (3 months) either on a Se(-) diet alone [Groups 2-5] or supplemented with selenium [Se(+)] (Group 6-8). After 9 weeks, Groups 3, 4, 6, 7 received sodium perchlorate [I(-); 1 month]. KI (1 mg/rat) was injected in Groups 4, 5, 7, 8. The animals were decapitated 3 days after the injections. RESULTS: FT4 was higher in serum of Se(-) rats than in that of Se(+). The differences of FT3 were not statistically significant. In I(-) Groups, the levels of FT3 and FT4 were very low. KI increased both thyroid hormones in I(-) rats but the effect was especially pronounced for FT3. KI decreased the weights of the glands, enlarged in the I(-) animals, both on Se(-) and Se(+) diet. Urine iodide concentrations were lower in Se(-) animals; KI increased ioduria. CONCLUSIONS: These data demonstrate that selenium and iodine deficiencies may play an essential role in thyroid hormone metabolism.

Effects of different antioxidants on lipid peroxidation in brain homogenates, induced by L-thyroxine administration in rats.

OBJECTIVE: It is known that thyrotoxicosis induces lipid peroxidation (LPO). In contrast, propylthiouracil (PTU), a thyrostatic drug is a well-known antioxidant. Also melatonin has been shown to protect against free radical-induced neuronal destruction. At the same time, it is generally accepted that the brain is the most vulnerable tissue to oxidative stress. METHODS: The goal of the study was to examine the components of LPO, i.e., conjugated dienes (CD), malondialdehyde (MDA) and Schiff's bases (SB), in the brain of male Wistar rats. Two experiments were performed, with two control groups created for each experiment: Group 1--intact animals and Group 2--animals injected with 0.9% NaCl. In Experiment I, the animals received L-thyroxine (L-T4) in a dose of 100 microg/kg BW, i.p., daily, for two weeks (Groups 3-5). After one week of L-T4 treatment, the following agents were added during a subsequent week: Group 4--PTU in drinking water (45 mg/kg BW/day); Group 5--melatonin (5 mg/kg BW, daily). In Experiment II, lasting 7 days, the animals were divided into the following groups: Group 1--intact animals; Group 2--animals injected with 0.9% NaCl; Group 3--PTU in drinking water (45 mg/kg BW/day); Group 4--melatonin (5 mg/kg BW, daily). RESULTS: In Experiment I, we observed a significantly higher SB level in saline treated animals and a significant increase in both CD and SB levels in rats treated with L-T4, compared to those in non treated control. CD levels were also elevated in rats treated with L-T4, compared to values in the saline only treated animals. Melatonin and PTU reduced CD levels and melatonin diminished SB levels, as compared to those in L-T4-treated rats. In Experiment II, we observed significantly higher CD, SB and MDA levels in saline treated rats, when compared to respective values in non treated control. Melatonin decreased CD levels, when compared to CD levels in both the non treated and saline injected controls. Additionally, melatonin reduced SB levels relative to change in the brains of saline treated rats. Furthermore, PTU decreased CD levels in brain homogenates compared to non-treated animals. CONCLUSIONS: (1) L-thyroxine administration stimulates LPO in the rat brain; (2) All the examined antioxidants decrease LPO in L-T4-administered animals; (3) All the examined antioxidants reduce the basal LPO; 4) Stress, when induced by handling, intensifies oxidative processes in the organism.