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At least 73 records · Page 4Linked to original sources
PubMed1980

Thymus-endocrine interactions during ageing.

The hypotesis of the thymus acting as biological clock for ageing is revisited. On the basis of data on the endocrine action of the gland, the age-dependent involution of the thymus is postulated to play a fundamental role on the deterioration of the immunological as well as the endocrine functions. Data either on beta-adrenergic responsiveness to Isoproterenol or on hormonal balance, tested on animal model with different degree of thymus efficiency, support this hypothesis.

Aging↗
PubMed2003

Aging alters circadian and light-induced expression of clock genes in golden hamsters.

Aging alters numerous aspects of circadian biology, including the amplitude of rhythms generated by the suprachiasmatic nuclei (SCN) of the hypothalamus, the site of the central circadian pacemaker in mammals, and the response of the pacemaker to environmental stimuli such as light. Although previous studies have described molecular correlates of these behavioral changes, to date only 1 study in rats has attempted to determine if there are age-related changes in the expression of genes that comprise the circadian clock itself. We used in situ hybridization to examine the effects of age on the circadian pattern of expression of a subset of the genes that comprise the molecular machinery of the circadian clock in golden hamsters. Here we report that age alters the 24-h expression profile of Clock and its binding partner Bmal1 in the hamster SCN. There is no effect of age on the 24-h profile of either Per1 or Per2 when hamsters are housed in constant darkness. We also found that light pulses, which induce smaller phase shifts in old animals than in young, lead to decreased induction of Per1, but not of Per2, in the SCN of old hamsters.

ARNTL Transcription Factors↗
PubMed2003

The expression of genes encoding visual components is regulated by a circadian clock, light environment and age in the honeybee (Apis mellifera).

The honeybee, Apis mellifera, has been used as a model to study the development of the visual system and adult bee behaviour. However, the regulation of the levels of visual component genes has never been addressed in this organism. We isolated honeybee cDNAs encoding green-sensitive opsin and visual arrestin and then measured their mRNA levels in honeybee workers. Both mRNAs fluctuate on a daily cycle that depends on a pacemaker that functions separately from the pacemaker which controls rhythmic locomotor activity. The cycling-patterns of opsin and arrestin mRNAs are different from each other and are modified by light. Furthermore, light exposure can increase the absolute levels of both mRNAs and the arrestin mRNA level is also dependent on age. Consistent with these results, both mRNA levels are higher in foragers than in in-hive bees under natural conditions. This study thus shows that the expression of genes encoding visual components is regulated by multiple factors and is adjusted to the honeybees' need for vision during the day, and throughout their lives. Comparison of data obtained with honeybees and other organisms indicates that there is a link between the regulation of phototransduction components and vision-related animal behaviour.

Aging↗
PubMed2006

Scaling and universality in the aging kinetics of the two-dimensional clock model.

We study numerically the aging dynamics of the two-dimensional p -state clock model after a quench from an infinite temperature to the ferromagnetic phase or to the Kosterlitz-Thouless phase. The system exhibits the general scaling behavior characteristic of nondisordered coarsening systems. For quenches to the ferromagnetic phase, the value of the dynamical exponents suggests that the model belongs to the Ising-type universality class. Specifically, for the integrated response function chi(t,s) approximately or = s(-a)chif(t/s), we find a(chi) consistent with the value a(chi)=0.28 found in the two-dimensional Ising model.

Journal Article↗
PubMed2000

Mitochondrial oxidative stress plays a key role in aging and apoptosis.

Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitochondrial production of hydroperoxide and the maximum life span of species. An important change in mitochondrial lipid composition is the age-related decrease found in cardiolipin content. The concurrent enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production of reactive oxygen species, which in turn would aggravate the oxidative damage to mitochondria. Moreover, superoxide radicals produced during mitochondrial respiration react with nitric oxide inside mitochondria to yield damaging peroxynitrite. Treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 761, protects against the age-associated oxidative damage to mtDNA and the oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver.

Aging↗
PubMed2006

Exploratory investigation of the effect of melatonin and caloric restriction on the temporal expression of murine hypothalamic transcripts.

Circadian rhythms of behaviour and gene expression are coupled to endogenous neuronal oscillators located in the hypothalamic suprachiasmatic nuclei (SCN), which are synchronised by the environmental light cycle. Besides light, other factors such as the pineal hormone melatonin, temperature and feeding have entraining properties. During senescence, the circadian system becomes weaker and susceptible to desynchronisation. It is unknown to what extent age-related changes are the result of the deterioration of the hypothalamic master clock. Supplementing ageing mice with melatonin as well as maintaining them on a hypocaloric diet extends the life span and delays age-related diseases. By means of DNA microarrays and the quantitative polymerase chain reaction, we have conducted an exploratory study to compare the effect of long-term melatonin substitution (MEL) and caloric restriction (CR) on circadian gene expression in hypothalamic samples, which contained the SCN as well as other important nuclei involved in nutrient balance, reproduction, and so on. Over 4% of the hypothalamic transcripts showed an overt circadian rhythm in expression, and many of these contain E boxes in their promoter regions, suggesting a direct regulation by circadian clock genes. MEL and CR significantly influenced some of these rhythmically expressed transcripts, but often in opposite ways. Importantly, our studies emphasise that the apparent direction of treatment effects (i.e. up-regulation versus down-regulation) depends on the time of day at which the samples are compared.

Aging↗
PubMed2001

Impaired expression of the mPer2 circadian clock gene in the suprachiasmatic nuclei of aging mice.

The expression of circadian clock genes was investigated in the suprachiasmatic nuclei (SCN) of young adult and old laboratory mice. Samples were taken at two time points, which corresponded to the expected maximum (circadian time 7 [CT7]) or minimum (CT21) of mPer mRNA expression. Whereas the young mice had a stable and well-synchronized circadian activity/rest cycle, the rhythms of old animals were less stable and were phase advanced. The expression of mPerl mRNA and mPer2 mRNA was rhythmic in both groups, with peak values at CT7. The levels of mClock and mCry1 mRNA were not different depending on the time of day and did not vary with age. In contrast, an age-dependent difference was found in the case of mPer2 (but not mPerl) mRNA expression, with the maximum at CT7 significantly lower in old mice. The decreased expression of mPer2 may be relevant for the observed differences in the overt activity rhythm of aged mice.

Age Factors↗
PubMed2003

Loss of circadian rhythmicity in aging mPer1-/-mCry2-/- mutant mice.

The mPer1, mPer2, mCry1, and mCry2 genes play a central role in the molecular mechanism driving the central pacemaker of the mammalian circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus. In vitro studies suggest a close interaction of all mPER and mCRY proteins. We investigated mPER and mCRY interactions in vivo by generating different combinations of mPer/mCry double-mutant mice. We previously showed that mCry2 acts as a nonallelic suppressor of mPer2 in the core clock mechanism. Here, we focus on the circadian phenotypes of mPer1/mCry double-mutant animals and find a decay of the clock with age in mPer1-/- mCry2-/- mice at the behavioral and the molecular levels. Our findings indicate that complexes consisting of different combinations of mPER and mCRY proteins are not redundant in vivo and have different potentials in transcriptional regulation in the system of autoregulatory feedback loops driving the circadian clock.

Aging↗
PubMed2004

Early neuropsychological correlates of later clock drawing and clock copying abilities among school aged children.

Although widely used in empirical study and bedside neuropsychological evaluation of geriatric populations, there is little literature on clock copying and drawing among children. However, existing research suggests that clock drawing tests (CDTs) may be effective and efficient tools for assessing neurocognitive development in children. This paper reports data on clock drawing on demand (CDT-D) and clock drawing to copy (CDT-C) among a non-clinical sample of elementary school aged children and identifies predictive relationships between earlier measures of executive function, visuo-construction, and visual-motor coordination and CDT performance 3 years later. Similar to findings with adult samples, analyses revealed better performance on copying than on drawing. Longitudinal analyses indicate that general intelligence significantly predicted performance on both tasks. Visual-motor coordination only predicted performance on the drawing on demand subtest of the CDT.

Adolescent↗
PubMed2026

Ensemble DNA methylation clock demonstrates Immune-metabolic aging signatures associated with mortality.

Aging is a multifactorial process that is best described in terms of the progressive acquisition of multiple layers of phenotypic changes, such as epigenetic modifications, inflammation, and metabolic dysregulation. DNA methylation clocks have been extensively used to construct epigenetic clocks based on the DNAm profiles that can be used to estimate biological age and predict age-associated outcomes. Nevertheless, the vast majority of clocks constructed so far have been based on linear models, which are unlikely to fully account for the heterogeneity and non-linearity of survival-related DNAm signatures. In this work, we constructed a heterogeneous stacked ensemble survival model based on DNAm data obtained from the Framingham Heart Study. We first identified 190 CpG loci using elastic net Cox regression and subsequently constructed a survival prediction model based on the fusion of five complementary survival models by means of a neural network meta-learner. The prediction power of the survival model was evaluated in an external validation cohort, where we observed strong performance for predicting all-cause mortality that significantly exceeded PhenoAge and was statistically comparable to GrimAge. These performance estimates were derived in cohorts of European ancestry and externally validated in postmenopausal women aged 50-79 years, and should therefore be interpreted as applicable only to demographically similar populations.

Humans↗
PubMed2026

Early life sugar rationing and ageing related diseases, biological ageing and mortality.

Early-life nutrition may influence lifelong ageing, yet human evidence is scarce. Using Britain's postwar sugar rationing as a natural experiment, we examine its long-term effects in 64,809 United Kingdom Biobank participants. Exposure to sugar rationing during the first 1,000 days of life is associated with a 9% lower incidence of hallmark-related disease, with a hazard ratio of 0.91 and a 95% confidence interval of 0.88-0.94, and a 19% lower risk of all-cause mortality, with a hazard ratio of 0.81 and a 95% confidence interval of 0.69-0.93. Mediation analysis indicates that the survival association is statistically mediated, by approximately 60%, through differences in incident hallmark-related disease. Rationed individuals show 1.0-1.2-year younger biological ages across multiple clocks and lower organ ages, particularly in the lung, heart, and liver. Proteomic profiling identifies 47 altered proteins, with enrichment of adenosine monophosphate-activated protein kinase and longevity pathways and suppression of mechanistic target of rapamycin signaling. These findings are consistent with international recommendations to limit free or added sugars from the World Health Organization, United States Dietary Guidelines, and American Heart Association, and may inform policy discussions related to sugar taxation and infant food and marketing policies under the United Nations 2030 Agenda.

Humans↗
PubMed2000

The role of Clock in the developmental expression of neuropeptides in the suprachiasmatic nucleus.

The suprachiasmatic nucleus (SCN) is the dominant circadian pacemaker in mammals. To understand better the ontogeny of mouse SCN and the role of the pacemaker in peptide expression, the authors examined the distribution of cells that were immunoreactive for vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) in wild type and Clock mutant mice at two developmental stages. Clock homozygous mice failed to show the dramatic increase in the number of VIP-immunoreactive (VIP-ir) neurons from postnatal day 6 (P6) to P30 that was found in the SCN of wild type mice. The number of AVP-ir neurons was relatively constant in the postnatal SCN but was significantly reduced in Clock/Clock mice. The effects of the Clock mutation varied with position in the SCN for both peptides. Densitometry of immunolabeled brains indicated that the Clock mutation reduced AVP expression specifically in the SCN and not in other brain areas. The SCN did not significantly change shape or size with age or Clock genotype. Taken together, these results indicate that the neonatal mouse SCN has its full complement of cells, some of which are not yet mature in their neuropeptide content. Furthermore, the observation that the Clock mutation appears to act on a subset of AVP and VIP cells suggests heterogeneity within these cell classes in the SCN.

Aging↗
PubMed2005

Light-induced melatonin suppression: age-related reduction in response to short wavelength light.

One of the possible causes of disturbed circadian rhythms and sleep in the elderly may be impaired photic input to the circadian clock. Age-related changes in lens density are known to reduce the transmission of short wavelength light, which has been shown to be most effective in suppressing nocturnal melatonin. The aim of the study therefore was to investigate age-related changes in melatonin suppression in response to short and medium wavelength light. Young premenopausal (n=13) and postmenopausal (n=21) women were exposed to 30 min of monochromatic light at two different wavelengths and irradiances (lambda(max) 456 nm: 3.8 and 9.8 microW/cm(2); lambda(max) 548 nm: 28 and 62 microW/cm(2)). Melatonin suppression was compared across light treatments and between age groups. Significantly reduced melatonin suppression was noted in the elderly subjects following exposure to short wavelength (456 nm) light compared to the young subjects. These results are likely to reflect age-related changes in lens density.

Adult↗
PubMed2003

Genes of aging.

According to developmental genetics theories, aging is a genetically programmed and controlled continuum of development and maturation. Being dynamic and malleable processes, development and aging are controlled not only by genes but also by environmental and epigenetic influences that predominate in the second half of life. Genetic mutations affect many phenotypes in flies, worms, rodents, and humans which share several diseases or their equivalents, including cancer, neurodegeneration, and infectious disorders as well as their susceptibility to them. Life span and stress resistance are closely linked. Oxidative stress actually constitutes a defined hypothesis of aging in that macromolecule oxidative damage accumulates with age and tends to be associated with life expectancy. DNA methylation, a force in the regulation of gene expression, is also one of the biomarkers of genetic damage. The mitotic clock of aging is marked, if not guided, by telomeres, essential genetic elements stabilizing natural chromosomic ends. The dream of humans to live longer, healthy lives is being tested by attempts to modify longevity in animal models, frequently by dietary manipulation. The quest continues to understand the mechanisms of healthy aging, one of the most compelling areas of research in the 21st century.

Aging↗