Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Desempenho reprodutivo, concentrações de progesterona e metabólitos lipídicos no pós-parto de vacas mestiças H/Z, submetidas a uma dieta hiperlipidêmica Reproductive performance, concentrations of progesterone and lipidic metabolites in the postpartum crossbred dairy cows submitted to a hyperlipidemic diet

Para avaliar o efeito de uma dieta hiperlipidêmica nos níveis séricos de metabólitos lipídicos e progesterona e no desempenho reprodutivo, 42 vacas mestiças foram submetidas a dois tratamentos: T1 (n=21) dieta-controle e T2 (n=21) dieta hiperlipidêmica, tendo como principal fonte de lipídios o grão de soja integral. Os intervalos médios para a primeira e segunda ovulações pós-parto foram 26,3 e 35,9 dias para os animais do T1 e 21,7 e 37,4 dias para os do T2. Os intervalos médios do parto ao início da atividade luteal, primeiro estro e primeiro ciclo estral normal foram, respectivamente, 29,9; 39,5; e 53,9 dias para T1 e 25,7; 33,3; e 52,3 dias para T2. A duração média do primeiro ciclo estral foi de 14,7 e 16,9 dias e do segundo de 19,8 e 19,5 dias para T1 e T2, respectivamente. As concentrações de progesterona nos ciclos estrais normais ocorridos durante o período de 90 dias pós-parto variaram de valores mínimos de 0,27 (T1) e 0,31 ng/mL (T2), nos dias 0 e 1 (dia 0 = ovulação), para valores máximos de 6,71 ng/mL (T1), nos dias 10 e 11, e 7,04 ng/mL (T2), nos dias -9 e --8, retornando a níveis basais (<1 ng/mL) nos dias -3 e -2. As concentrações médias de colesterol total e colesterol HDL para T1 e T2 foram, respectivamente, 100,74 e 67,3 mg/dL e 162,25 e 95,8 mg/dL. O efeito de hipercolesterolemia da dieta foi confirmado nesta pesquisa, mas sem nenhum aumento nas concentrações de progesterona e desempenho reprodutivo.<br>To evaluate the effect of a hiperlipidemic diet on the reproductive performance, lipidic metabolites and serum progesterone levels, 42 Holstein-Zebu crossbred cows were submitted to two treatments: T1 (n=21), control diet, and T2 (n=21), hyperlipidemic diet, consisting mainly on whole soybean. The mean intervals to the first and second postpartum ovulations were 26.3 and 35.9 days for animals of T1 and 21.7 and 37.4 days for those of T2. The average intervals from calving to onset of the luteal activity, first estrus and first normal estrus cycle length were respectively, 29.9, 39.5, and 53.9 days for T1 and 25.7, 33.3, and 52.3 days for T2. The average first estrus cycle was 14.7 and 16.9 days and of the second 19.8 and 19.5 days for T1 and T2, respectively. The concentrations of serum progesterone in the normal estrus cycles during the period of 90 days postpartum, varied from minimum values of 0.27 ng/mL (T1) to 0.31 ng/mL (T2) on the days 1 and 0 (day 0 = ovulation) to maximum values of 6.71 ng/mL (T1) on days 10 and 11 and 7.04 ng/mL (T2) on days -9 and --8, returning to basal levels (<1 ng/mL) on days -3 e -2. The total cholesterol and HDL average concentrations for T1 e T2 were 100.74 and 67.3 mg/dL (T1) and 162.25 and 95.8 mg/dL (T2) respectively. The hypercholesterolemic effect of the diet was confirmed, but without any increase in the concentration of progesterone and reproductive performance