Age Differences In Effects Research Articles

Altered White Matter Microstructure in Adolescents and Adults with Bulimia Nervosa.

Previous data suggest structural and functional deficits in frontal control circuits in adolescents and adults with bulimia nervosa (BN), but less is known about the microstructure of white matter in these circuits early in the course of the disorder. Diffusion tensor imaging (DTI) data were acquired from 28 female adolescents and adults with BN and 28 age- and BMI-matched healthy female participants. Tract-based spatial statistics (TBSS) was used to detect group differences in white matter microstructure and explore the differential effects of age on white matter microstructure across groups. Significant reductions in fractional anisotropy (FA) were detected in the BN compared with healthy control group in multiple tracts including forceps minor and major, superior longitudinal, inferior fronto-occipital, and uncinate fasciculi, anterior thalamic radiation, cingulum, and corticospinal tract. FA reductions in forceps and frontotemporal tracts correlated inversely with symptom severity and Stroop interference in the BN group. These findings suggest that white matter microstructure is abnormal in BN in tracts extending through frontal and temporoparietal cortices, especially in those with the most severe symptoms. Age-related differences in both FA and RD in these tracts in BN compared with healthy individuals may represent an abnormal trajectory of white matter development that contributes to the persistence of functional impairments in self-regulation in BN.

Region-specific changes in presynaptic agmatine and glutamate levels in the aged rat brain

During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region-specific manner during the aging process. The gross tissue content of agmatine in the prefrontal cortex (PFC) of aged rat brains is decreased whereas levels in the temporal cortex (TE) are increased. However, it is not known whether these changes in gross tissue levels are also mirrored by changes in agmatine levels at synapses and thus could potentially contribute to altered synaptic function with age. In the present study, agmatine levels in presynaptic terminals in the PFC and TE regions (300 terminals/region) of young (3month; n=3) and aged (24month; n=3) brains of male Sprague–Dawley rats were compared using quantitative post-embedding immunogold electron-microscopy. Presynaptic levels of agmatine were significantly increased in the TE region (60%; p<0.001) of aged rats compared to young rats, however no significant differences were detected in synaptic levels in the PFC region. Double immunogold labeling indicated that agmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine-immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms.

Effect of Advancing Age and Multiple Chronic Conditions on Mortality in Patients with End-Stage Renal Disease after Implantable Cardioverter-Defibrillator Placement.

There is insufficient information on the effect that advancing age and multiple chronic conditions (MCC) have on mortality after placement of an implantable cardioverter-defibrillator in patients with end-stage renal disease (ESRD) vs non-ESRD. To assess whether a differential effect of age and MCC exists between ESRD and non-ESRD. Population-based, retrospective cohort study using data from the national Kaiser Permanente Cardiac Device Registry of patients who underwent placement of an implantable cardioverter-defibrillator between January 1, 2007, and December 31, 2013. All-cause mortality. Of 7825 patients with implantable cardioverter-defibrillator placement, ESRD-affected patients constituted 4.0% of the cohort (n = 311), were similar in age (p = 0.91), and presented with a larger comorbidity burden (3.3 ± 1.3 vs 2.4 ± 1.5, p < 0.001). The effect of advancing age (every 5 years) on mortality in the ESRD cohort (hazard ratio [HR] = 1.11, 95% confidence interval [CI] = 1.03-1.20) was less than in the non-ESRD cohort (HR = 1.28, 95% CI = 1.25-1.32). Similarly, the effect of each additional comorbidity in the ESRD cohort was less (HR = 1.04, 95% CI = 0.91-1.19) than in the non-ESRD group (HR = 1.20, 95% CI = 1.16-1.25). Lastly, ESRD was independently associated with a 3-fold greater hazard of mortality. Advancing age and increasing number of MCC have a differential effect on mortality risk in patients with ESRD compared with their non-ESRD counterparts. Future studies should focus on assessment of nonlinear relationships of age, MCC, and naturally occurring clusters of MCC on mortality.

Are medical marijuana users different than recreational marijuana users?

s / Drug and Alcohol Dependence 156 (2015) e102–e182 e141 and fewerpercent days smoking (8% fewer,p 16 yrs). This study investigated differential effects of age of smokingonset on response impulsivity and inhibitory control using a novel smoking Go/NoGo task (Luijten et al., 2011). Methods: Adult EOS (n=6) and LOS (n=10) in acute nicotine withdrawal and adult non-smokers (NS;n=10) were shown Smoking or Non-Smoking images with either a blue (Go) or yellow (NoGo) frame. Participants were instructed to respond to blueframed Go trials quickly and accurately, and withhold responding for yellow-framed NoGo trials. Each Smoking and Non-Smoking image was shown 3 times as a Go stimulus and once as a NoGo stimulus. Results: EOS and LOS exhibited more Go errors (p<0.01) and a greater false alarm rate (p<0.01) than NS. EOS and LOS showed loweroverallGo responseaccuracy (p<0.01), andEOSalsoexhibited lower Smoking Go accuracy (p<0.03), than NS. EOS and LOS exhibited lower Smoking NoGo accuracy (p<0.02), and LOS also showed lower Non-Smoking NoGo accuracy (p<0.02), than NS. Smoking Go accuracy and Non-Smoking NoGo accuracy were each correlated with age of smoking onset (p<0.01) and daily cigarettes smoked (p<0.02). Conclusions: EOShaddifficulty responding accurately to Smoking Go stimuli, suggesting that these distracting images disrupted attention to task demands. In contrast, LOS had difficultywithholding responses to both Smoking and NonSmoking NoGo stimuli, indicating greater impulsivity and deficits in inhibitory control, regardless of category. Collectively, preliminary findings suggest age of smoking onset differentially impacts task-related attention and response inhibition, thus individualized cognitive approaches may improveexecutive function in smokers in treatmentprograms. Financial support: K01DA034028 (YM). http://dx.doi.org/10.1016/j.drugalcdep.2015.07.386 Risks associated with nonmedical prescription opioid use: Transition to heroin use and drug injection, overdose and hepatitis C Pedro Mateu-Gelabert, Honoria Guarino, Lauren Jessell, Cassandra Syckes, Samuel R. Friedman Institute for Infectious Disease Research, National Development and Research Institutes, Inc, New York,

Gender Differences in the Development of Sexual Excitation and Inhibition Through the Life Course: Preliminary Findings from a Representative Study in Flanders

The dual control model proposes that there are individual differences in the propensity for sexual excitation and sexual inhibition. Research to date has considered the effect of age on these traits as a simple linear effect, and studies examining gender differences in age effects are lacking. There are, however, indications that the associations of age with excitation and inhibition are nonlinear and that there might be gender differences in these associations. The aim of this study was to examine how these traits develop through an individual’s life and whether there are gender differences in this development. In this study we applied polynomial regression analyses to examine the interaction effects of age and gender on sexual excitation and inhibition. We used data from a representative cross-sectional survey on sexual health in Flanders (N = 1,825; mean age = 43.77; SD = 17.98). Most of the associations of excitation and inhibition with age were nonlinear, and there were substantial gender differences in these associations. This indicates that the interplay between age, gender, and excitation and inhibition should be taken into account in research on (dys)functional sexuality.

Neural correlates of positive and negative performance feedback in younger and older adults.

BackgroundRecent studies with younger adults have shown that performance feedback can serve as a reward, and it elicits reward-related brain activations. This study investigated whether performance feedback is processed similarly in younger and older adults and whether there are differential aging effects for positive and negative performance feedback.MethodsWe used event-related fMRI in a choice reaction-time task and provided performance feedback after each trial.ResultsAlthough younger and older adults differed in task-related activation, they showed comparable reward-related activation. Positive performance feedback elicited the strongest striatal and amygdala activation, which was reflected behaviorally in slightly faster reaction times.ConclusionsThese results suggest that performance feedback serves as a reward in both younger and older adults.

Longitudinal changes in hematocrit in hypertensive chronic kidney disease: results from the African-American Study of Kidney Disease and Hypertension (AASK).

Anemia is common in chronic kidney disease (CKD) and associated with poor outcomes. In cross-sectional studies, lower estimated glomerular filtration rate (eGFR) has been associated with increased risk for anemia. The aim of this study was to determine how hematocrit changes as eGFR declines and what factors impact this longitudinal association. We followed 1094 African-Americans with hypertensive nephropathy who participated in the African-American Study of Kidney Disease and Hypertension. Mixed effects models were used to determine longitudinal change in hematocrit as a function of eGFR. Interaction terms were used to assess for differential effects of age, gender, baseline eGFR, baseline proteinuria, malnutrition and inflammation on eGFR-associated declines in hematocrit. In sensitivity analyses, models were run using iGFR (by renal clearance of I(125) iothalamate) in place of eGFR. At baseline, mean hematocrit was 39% and 441 (40%) individuals had anemia. The longitudinal relationship between eGFR and hematocrit differed by baseline eGFR and was steeper when baseline eGFR was <45 mL/min/1.73 m(2). For example, the absolute decline in hematocrit per 10 mL/min/1.73 m(2) decline in longitudinal eGFR was -3.7, -1.3 and -0.5% for baseline eGFR values of 20, 40 and 60 mL/min/1.73 m(2), respectively (P < 0.001 comparing the longitudinal association between baseline eGFR = 40 or 60 versus baseline eGFR = 20 mL/min/1.73 m(2)). Similarly, male sex, younger age (<65 years) and higher baseline proteinuria (protein-to-creatinine ratio >0.22) were associated with greater hematocrit declines per unit decrease in longitudinal eGFR compared with female sex, older age and low baseline proteinuria, respectively (P-interaction <0.05 for each comparison). The longitudinal eGFR-hematocrit association did not differ by body mass index, serum albumin or C-reactive protein. Men, younger individuals and those with low baseline eGFR (<45 mL/min/1.73 m(2)) or baseline proteinuria are particularly at risk for eGFR-related declines in hematocrit.

Study of cardiovascular disease biomarkers among tobacco consumers, part 2: biomarkers of biological effect

An age-stratified, cross-sectional study was conducted in the US among healthy adult male cigarette smokers, moist snuff consumers, and non-tobacco consumers to evaluate cardiovascular biomarkers of biological effect (BoBE). Physiological assessments included flow-mediated dilation, ankle-brachial index, carotid intima-media thickness and expired carbon monoxide. Approximately one-half of the measured serum BoBE showed statistically significant differences; IL-12(p70), sICAM-1 and IL-8 were the BoBE that best differentiated among the three groups. A significant difference in ABI was observed between the cigarette smokers and non-tobacco consumer groups. Significant group and age effect differences in select biomarkers were identified.

Differential effects of age and type 2 diabetes on dynamic vs. peak response of pulmonary oxygen uptake during exercise.

We investigated if the magnitude of the type 2 diabetes (T2D)-induced impairments in peak oxygen uptake (V̇o2) and V̇o2 kinetics was affected by age. Thirty-three men with T2D (15 middle-aged, 18 older), and 21 nondiabetic (ND) men (11 middle-aged, 10 older) matched by age were recruited. Participants completed four 6-min bouts of constant-load cycling at 80% ventilatory threshold for the determination of V̇o2 kinetics. Cardiac output (inert-gas rebreathing) was recorded at rest and 30 and 240 s during two additional bouts. Peak V̇o2 (determined from a separate graded test) was significantly (P < 0.05) reduced in middle-aged and older men with T2D compared with their respective ND counterparts (middle-aged, 3.2 ± 0.5 vs. 2.5 ± 0.5 l/min; older, 2.7 ± 0.4 vs. 2.4 ± 0.4 l/min), and the magnitude of these impairments was not affected by age. However, the time constant of phase II of the V̇o2 response was only slowed (P < 0.05) in middle-aged men with T2D compared with healthy counterparts, whereas it was similar among older men with and without T2D (middle-aged, 26.8 ± 9.3 vs. 41.6 ± 12.1 s; older, 40.5 ± 7.8 vs. 41.1 ± 8.5 s). Similarly, the "gains" in systemic vascular conductance (estimated from the slope between cardiac output and mean arterial pressure responses) were lower (P < 0.05) in middle-aged men with T2D than ND controls, but similar between the older groups. The results suggest that the mechanisms by which T2D induces significant reductions in peak exercise performance are linked to a slower dynamic response of V̇o2 and reduced systemic vascular conductance responses in middle-aged men, whereas this is not the case in older men.

Restricted loss of olivocochlear but not vestibular efferent neurons in the senescent gerbil (Meriones unguiculatus).

Degeneration of hearing and vertigo are symptoms of age-related auditory and vestibular disorders reflecting multifactorial changes in the peripheral and central nervous system whose interplay remains largely unknown. Originating bilaterally in the brain stem, vestibular and auditory efferent cholinergic projections exert feedback control on the peripheral sensory organs, and modulate sensory processing. We studied age-related changes in the auditory and vestibular efferent systems by evaluating number of cholinergic efferent neurons in young adult and aged gerbils, and in cholinergic trigeminal neurons serving as a control for efferents not related to the inner ear. We observed a significant loss of olivocochlear (OC) neurons in aged compared to young adult animals, whereas the overall number of lateral superior olive (LSO) cells was not reduced in aging. Although the loss of lateral and medial olivocochlear (MOC) neurons was uniform and equal on both sides of the brain, there were frequency-related differences within the lateral olivocochlear (LOC) neurons, where the decline was larger in the medial limb of the superior olivary nucleus (high frequency representation) than in the lateral limb (middle-to-low frequency representation). In contrast, neither the number of vestibular efferent neurons, nor the population of motor trigeminal neurons were significantly reduced in the aged animals. These observations suggest differential effects of aging on the respective cholinergic efferent brainstem systems.

Circadian clocks in rat skin and dermal fibroblasts: differential effects of aging, temperature and melatonin.

As a peripheral tissue localized at the interface between internal and external environments, skin performs functions which are critical for the preservation of body homeostasis, in coordination with environmental changes. Some of these functions undergo daily variations, such as temperature or water loss, suggesting the presence of time-keeping mechanisms. Rhythmic functions are controlled by a network of circadian oscillators present virtually in every cell and coordinated by the central clock located in the suprachiasmatic nuclei. At the molecular level, circadian rhythms are generated by conserved transcriptional-translational feedback loops involving several clock genes, among which Per1 and Per2 play a central role. Here we characterize clock activity in skin of the transgenic Per1-luciferase rat during postnatal development and adulthood, by real-time recording of bioluminescence in explants and primary dermal fibroblasts, and report marked transformation in circadian properties, from early life to aging. Using primary dermal fibroblast cultures we provide evidence that melatonin treatment phase dependently increases the amplitude of circadian oscillations and that ambient temperature impacts on their period, with slight overcompensation. Together, these findings demonstrate that skin contains a self-sustained circadian clock undergoing age-dependent changes. Dermal fibroblasts, one of the major skin cell types, also exhibit robust, yet specific, circadian rhythmicity which can be fine-tuned by both internal (melatonin) and external (temperature) factors.

Differential effects of age and intestinal helminthiasis on positivity rate of skin prick reaction to environmental allergens among Nigerians

Background: Skin prick testing (SPT) conventionally used to investigate immediate type (type 1) hypersensitivity to allergens is reported to be affected by varying factors. It is hypothesized by present study that immunomodulation of T-cell by parasitic helminthic infection may affect skin prick reaction.Study Objectives: The primary objective of this cross-sectional study is to determine the prevalence of intestinal helminthiasis and its effect on the outcome of SPT to environmental allergens.Participants, Materials and Methods: Skin prick test was performed on 296 residents (113 adults and 183 children) rural and urban parts of Ibadan, South-West Nigeria. Stool specimen was also collected and examined for ova, cyst and larvae of intestinal worms.Results and Conclusion: The prevalence of intestinal helminthiasis was 20.8% and 21.2% in children and adults respectively. Prevalence of intestinal helminthiasis in adults from rural settings was significantly higher when compared with adults from urban settings. Significantly higher positive skin test to dog allergen was observed in helminth infected participants when compared to uninfected participants. Furthermore, significantly higher positive skin test to cockroach, mite, mold, and mouse allergen was observed in adults when compared to children. This suggests that the intestinal helminthiasis is found among all age groups in this region, but do not affect skin reaction to environmental allergens as much as ages of participants.

Brief Report: Phenotypic Differences and their Relationship to Paternal Age and Gender in Autism Spectrum Disorder.

Two modes of inheritance have been proposed in autism spectrum disorder, transmission though pre-existing variants and de novo mutations. Different modes may lead to different symptom expressions in affected individuals. De novo mutations become more likely with advancing paternal age suggesting that paternal age may predict phenotypic differences. To test this possibility we measured IQ, adaptive behavior, and autistic symptoms in 830 probands from simplex families. We conducted multiple linear regression analysis to estimate the predictive value of paternal age, maternal age, and gender on behavioral measures and IQ. We found a differential effect of parental age and sex on repetitive and restricted behaviors. Findings suggest effects of paternal age on phenotypic differences in simplex families with ASD.

Aging and insulin signaling differentially control normal and tumorous germline stem cells

Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC–male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging.

The influence of age of onset and acute anabolic steroid exposure on cognitive performance, impulsivity, and aggression in men.

The name of author Heather Berlin omitted a middle initial in the byline and author note and should appear as Heather A. Berlin.] A growing translational literature suggests that adolescent exposure to anabolic-androgenic steroids (AASs) leads to increased aggression and impulsivity. However, little is known about the cognitive effects of AASs among AAS users or the differences between adolescent- and adult-onset users. This study provides a test of the effects of acute naturalistic AAS use and age of onset (adolescent vs. adult) on measures of inhibitory control, planning and attention, and decision making. Seventy-one active adult male AAS users completed self-report measures of impulsivity and aggression, and a subsample (11 adolescent onset vs. 11 adult onset) matched on current age were administered 4 computerized tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) (Cambridge Cognition, 2002) and the Iowa Gambling Task (Stanton, Liening, & Schultheiss, 2011). Multiple regression analyses and a series of 2 (adolescent vs. adult) × 2 (on-cycle vs. off-cycle) analyses of variance (ANOVAs) were used to examine the differential effects of age of onset and acute drug use on cognition and behavior. Regression analyses revealed larger on-cycle effects for adolescent users than adult users. Subsample analyses indicated that on-cycle users performed less well on cognitive measures of inhibitory control and attention, but not on tests of planning or decision making. Adolescent onset was associated with greater impulsivity and more acute sensitivity to AAS effects on attention. These preliminary findings suggest the possibility that acute AAS use is associated with some differences in inhibitory control and impulsivity and to a lesser degree, aggression. These effects may be more potent for those initiating AAS use in adolescence.

Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan.

Hippocampal abnormalities have been demonstrated in schizophrenia. It is unclear whether these abnormalities worsen with age, and whether they affect cognition and function. To determine whether hippocampal abnormalities in chronic schizophrenia are associated with age, cognition and socio-occupational function. Using 3 T magnetic resonance imaging we scanned 100 persons aged 19-82 years: 51 were out-patients with stable schizophrenia at least 2 years after diagnosis and 49 were healthy volunteers matched for age and gender. Automated analysis was used to determine hippocampal volume and shape. There were differential effects of age in the schizophrenia and control samples on total hippocampal volume (group × age interaction: F(1,95) = 6.57, P = 0.012), with steeper age-related reduction in the schizophrenia group. Three-dimensional shape analysis located the age-related deformations predominantly in the mid-body of the hippocampus. In the schizophrenia group similar patterns of morphometric abnormalities were correlated with impaired cognition and poorer socio-occupational function. Hippocampal abnormalities are associated with age in people with chronic schizophrenia, with a steeper decline than in healthy individuals. These abnormalities are associated with cognitive and functional deficits, suggesting that hippocampal morphometry may be a biomarker for cognitive decline in older patients with schizophrenia.

Glucose administration and cognitive function: differential effects of age and effort during a dual task paradigm in younger and older adults.

Current research suggests that glucose facilitates performance on cognitive tasks which possess an episodic memory component and a relatively high level of cognitive demand. However, the extent to which this glucose facilitation effect is uniform across the lifespan is uncertain. This study was a repeated measures, randomised, placebo-controlled, cross-over trial designed to assess the cognitive effects of glucose in younger and older adults under single and dual task conditions. Participants were 24 healthy younger (average age 20.6 years) and 24 healthy older adults (average age 72.5 years). They completed a recognition memory task after consuming drinks containing 25 g glucose and a placebo drink, both in the presence and absence of a secondary tracking task. Glucose enhanced recognition memory response time and tracking precision during the secondary task, in older adults only. These findings do not support preferential targeting of hippocampal function by glucose, rather they suggest that glucose administration differentially increases the availability of attentional resources in older individuals.

Atypical Frontal–Striatal–Thalamic Circuit White Matter Development in Pediatric Obsessive-Compulsive Disorder

Atypical development of frontal-striatal-thalamic circuitry (FSTC) has been hypothesized to underlie the early course of obsessive-compulsive disorder (OCD); however,the development of FSTC white matter tracts remains to be studied in young patients. Toaddress this gap, we scanned 36 patients with pediatric OCD compared to 27 healthy controls, aged 8 to 19 years, with diffusion tensor imaging (DTI) to measure fractional anisotropy (FA), an index of white matter coherence. Tract-based spatial statistics (TBSS) were used to test differential effects of age on FA, across the whole brain, in those with OCD compared to healthy youth, followed by analyses in a priori regions of interest (anterior corpus callosum, anterior cingulum bundle, and anterior limb of the internal capsule [ALIC]) to further characterize developmental differences between groups. Patients with OCD showed more pronounced age-related increases in FA than controls in regions of interest, as well as several other white matter tracts. In patients, greater FA in anterior cingulum bundle correlated with more severe symptoms after controlling for age. Our findings support theories of atypical FSTC maturation in pediatric OCD by providing the first evidence for altered trajectories of white matter development in anterior corpus callosum, anterior cingulum bundle, and ALIC in young patients. Steeper age-related increases of FA in these and other select white matter tracts in OCD, compared to those in healthy controls, may derive from an early delay in white matter development and/or prolonged white matter growth; however, confirmation of these possibilities awaits longitudinal work.

Effect of age on human-computer-interface control via neck electromyography.

The purpose of this study was to determine the effect of age on visuomotor tracking using submental and anterior neck surface electromyography (sEMG) to assess feasibility of computer control via neck musculature, which allows people with little remaining motor function to interact with computers. Thirty-two healthy adults participated: 16 younger adults aged 18–29 years and 16 older adults aged 69–85 years. Participants modulated sEMG to achieve targets presented at different amplitudes using real-time visual feedback. Root mean squared (RMS) error was used to quantify tracking performance. RMS error was increased for older adults relative to younger adults. Older adults demonstrated more RMS error than younger adults as a function of increasing target amplitude. The differential effects of age found on static tracking performance in anterior neck musculature suggest more difficult translation of human–computer interfaces controlled using anterior neck musculature for static tasks to older populations.

Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep

The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep.