Dataset Information

Perturbations in growth trajectory due to early diet affect age-related deterioration in performance.

ABSTRACT: Fluctuations in early developmental conditions can cause changes in growth trajectories that subsequently affect the adult phenotype. Here, we investigated whether compensatory growth has long-term consequences for patterns of senescence.Using three-spined sticklebacks (Gasterosteus aculeatus), we show that a brief period of dietary manipulation in early life affected skeletal growth rate not only during the manipulation itself, but also during a subsequent compensatory phase when fish caught up in size with controls.However, this growth acceleration influenced swimming endurance and its decline over the course of the breeding season, with a faster decline in fish that had undergone faster growth compensation.Similarly, accelerated growth led to a more pronounced reduction in the breeding period (as indicated by the duration of sexual ornamentation) over the following two breeding seasons, suggesting faster reproductive senescence. Parallel experiments showed a heightened effect of accelerated growth on these age-related declines in performance if the fish were under greater time stress to complete their compensation prior to the breeding season.Compensatory growth led to a reduction in median life span of 12% compared to steadily growing controls. While life span was independent of the eventual adult size attained, it was negatively correlated with the age-related decline in swimming endurance and sexual ornamentation.These results, complementary to those found when growth trajectories were altered by temperature rather than dietary manipulations, show that the costs of accelerated growth can last well beyond the time over which growth rates differ and are affected by the time available until an approaching life-history event such as reproduction.

SUBMITTER: Lee WS

PROVIDER: S-EPMC4994260 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Perturbations in growth trajectory due to early diet affect age-related deterioration in performance.

Lee Who-Seung WS Monaghan Pat P Metcalfe Neil B NB

Functional ecology 20150829 4

Fluctuations in early developmental conditions can cause changes in growth trajectories that subsequently affect the adult phenotype. Here, we investigated whether compensatory growth has long-term consequences for patterns of senescence.Using three-spined sticklebacks (<i>Gasterosteus aculeatus</i>), we show that a brief period of dietary manipulation in early life affected skeletal growth rate not only during the manipulation itself, but also during a subsequent compensatory phase when fish ca ...[more]

PMID: 27610000

Similar Datasets

Project description:Primary age-related tauopathy is increasingly recognized as a separate neuropathological entity different from Alzheimer's disease. Both share the neuropathological features of tau aggregates and neuronal loss in the temporal lobe, but primary age-related tauopathy lacks the requisite amyloid plaques central to Alzheimer's disease. While both have similar clinical presentations, individuals with symptomatic primary age-related tauopathy are commonly of more advanced ages with milder cognitive dysfunction. Direct comparison of the neuropsychological trajectories of primary age-related tauopathy and Alzheimer's disease has not been thoroughly evaluated and thus, our objective was to determine how cognitive decline differs longitudinally between these two conditions after the onset of clinical symptoms. Data were obtained from the National Alzheimer's Coordinating Center on participants with mild cognitive impairment at baseline and either no neuritic plaques (i.e. primary age-related tauopathy) or moderate to frequent neuritic plaques (i.e. Alzheimer neuropathological change) at subsequent autopsy. For patients with Alzheimer's disease and primary age-related tauopathy, we compared rates of decline in the sum of boxes score from the CDR® Dementia Staging Instrument and in five cognitive domains (episodic memory, attention/working memory, executive function, language/semantic memory, and global composite) using z-scores for neuropsychological tests that were calculated based on scores for participants with normal cognition. The differences in rates of change were tested using linear mixed-effects models accounting for clinical centre clustering and repeated measures by individual. Models were adjusted for sex, age, education, baseline test score, Braak stage, apolipoprotein ?4 (APOE ?4) carrier status, family history of cognitive impairment, and history of stroke, hypertension, or diabetes. We identified 578 participants with a global CDR of 0.5 (i.e. mild cognitive impairment) at baseline, 126 with primary age-related tauopathy and 452 with Alzheimer's disease. Examining the difference in rates of change in CDR sum of boxes and in all domain scores, participants with Alzheimer's disease had a significantly steeper decline after becoming clinically symptomatic than those with primary age-related tauopathy. This remained true after adjusting for covariates. The results of this analysis corroborate previous studies showing that primary age-related tauopathy has slower cognitive decline than Alzheimer's disease across multiple neuropsychological domains, thus adding to the understanding of the neuropsychological burden in primary age-related tauopathy. The study provides further evidence to support the hypothesis that primary age-related tauopathy has distinct neuropathological and clinical features compared to Alzheimer's disease.

Project description:Age-related deterioration of pacemaker function has been documented in mammals, including humans. In aged isolated sinoatrial node tissues and cells, reduction in the spontaneous action potential (AP) firing rate was associated with deterioration of intracellular and membrane mechanisms; however, their relative contribution to age-associated deficient pacemaker function is not known. Interestingly, pharmacological interventions that increase posttranslation modification signaling activities can restore the basal and maximal AP firing rate, but the identities of the protein targets responsible for AP firing rate restoration are not known. Here, we developed a numerical model that simulates the function of a single mouse pacemaker cell. In addition to describing membrane and intracellular mechanisms, the model includes descriptions of autonomic receptor activation pathways and posttranslation modification signaling cascades. The numerical model shows that age-related deterioration of pacemaker function is related to impaired intracellular and membrane mechanisms: HCN4, T-type channels, and phospholamban functions, as well as the node connecting these mechanisms, i.e., intracellular Ca2+ and posttranslation modification signaling. To explain the restored maximal beating rate in response to maximal phosphodiesterase (PDE) inhibition, autonomic receptor stimulation, or infused cyclic adenosine monophosphate (cAMP), the model predicts that phospholamban phosphorylation by protein kinase A (PKA) and HCN4 sensitivity to cAMP are altered in advanced age. Moreover, alteration in PKA and cAMP sensitivity can also explain age-reduced sensitivity to PDE inhibition and autonomic receptor stimulation. Finally, the numerical model suggests two pharmacological approaches and one gene manipulation method to restore the basal beating rate of aged pacemaker cells to that of normal adult cells. In conclusion, our numerical model shows that impaired membrane and intracellular mechanisms and the nodes that couple them can lead to deteriorated pacemaker function. By increasing posttranslation modification signaling, the deteriorated basal and maximal age-associated beating rate can be restored to adult levels.

Project description:Background: Motor progression varies even among those with a single diagnosis such as Parkinson's disease (PD) and little is known about the trajectory of motor signs prior to death. Understanding deterioration patterns may help clinicians counsel patients and proactively plan interdisciplinary care, including palliative care. The objective of this study was to examine and describe Unified Parkinson's Disease Rating Scale motor score (UPDRS-III) trajectories at the end of life in PD. Methods: A retrospective chart review was performed for deceased PD patients who attended the Parkinson and Movement Disorders Program at the University of Alberta for at least 5 years between 1999 and 2018. UPDRS-III scores were recorded for all visits. Trajectory patterns were visualized with Loess curves stratified by sex and age at diagnosis. Piecewise linear models were used to individually model the UPDRS-III scores, and the trajectories obtained were clustered based on their features. Results: Among the 202 charts reviewed, 84 meeting inclusion criteria were analyzed. The UPDRS-III increased over time regardless of sex and age. Distinct trajectory variations present in PD (e.g., Consistent Deterioration, Stability-Deterioration, Improvement-Deterioration, Deterioration-Improvement-Deterioration) were identified. Twenty-five percent of the patients were classified as Undetermined/Irregular trajectories. In addition, regardless of trajectory type, many patients experienced a steep increase in UPDRS-III approaching death. Those with disease diagnosis after age 65 years had a shorter survival time, compared to PD patients with a younger age of onset. Conclusion: Our study identified dominant types of motor trajectory in PD that can help clinicians understand their patients' course of illness. This information can help counsel patients regarding the variability in motor deterioration and should alert physicians to recognize a terminal decline. Age of disease onset was correlated with survival time.

Dataset Information

Perturbations in growth trajectory due to early diet affect age-related deterioration in performance.

Publications

Perturbations in growth trajectory due to early diet affect age-related deterioration in performance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets