Function In Adult Life Research Articles

Developmental remodeling repurposes larval neurons for sexual behaviors in adult Drosophila

Most larval neurons in Drosophila are repurposed during metamorphosis for functions in adult life, but their contribution to the neural circuits for sexually dimorphic behaviors is unknown. Here, we identify two interneurons in the nerve cord of adult Drosophila females that control ovipositor extrusion, a courtship rejection behavior performed by mated females. We show that these two neurons are present in the nerve cord of larvae as mature, sexually monomorphic interneurons. During pupal development, they acquire the expression of the sexual differentiation gene, doublesex; undergo doublesex-dependent programmed cell death in males; and are remodeled in females for functions in female mating behavior. Our results demonstrate that the neural circuits for courtship in Drosophila are built in part using neurons that are sexually reprogrammed from former sex-shared activities in larval life.

Can exposure to lisdexamfetamine dimesylate from juvenile period to peripubertal compromise male reproductive parameters in adult rats?

Lisdexamfetamine (LDX) is a d-amphetamine prodrug used to treat attention deficit and hyperactivity disorder, a common neurodevelopmental disorder in children and adolescents. Due to its action mediated by elevated levels of catecholamines, mainly dopamine and noradrenaline, which influence hormonal regulation and directly affect the gonads, this drug may potentially disrupt reproductive performance. This study evaluated the effects of exposure to LDX from the juvenile to peripubertal period (critical stages of development) on systemic and reproductive toxicity parameters in male rats. Male Wistar rats (23 days old) were treated with 0; 5.2; 8.6 or 12.1 mg/kg/day of LDX from post-natal day (PND) 23 to 53, by gavage. LDX treatment led to reduced daily food and water consumption, as well as a decrease in social behaviors. The day of preputial separation remained unaltered, although the treated animals exhibited reduced weight. At PND 54, the treated animals presented signs of systemic toxicity, evidenced by a reduction in body weight gain, increase in the relative weight of the liver, spleen, and seminal gland, reduction in erythrocyte and leukocyte counts, reduced total protein levels, and disruptions in oxidative parameters. In adulthood, there was an increase in immobile sperm, reduced sperm count, morphometric changes in the testis, and altered oxidative parameters, without compromising male sexual behavior and fertility. These findings showed that LDX-treatment during the juvenile and peripubertal periods induced immediate systemic toxicity and adversely influenced reproductive function in adult life, indicating that caution is necessary when prescribing this drug during the peripubertal phase.

Associations between recalled childhood gender nonconformity and adult sexual dysfunction in Denmark: baseline assessment in the Project SEXUS cohort study.

Sexual dysfunctions may negatively affect an individual's self-perceived womanhood or manhood, but whether gender nonconformity in childhood or adolescence can influence adult sexual functioning has not been examined so far. To explore the possible link between recalled childhood gender nonconformity and sexual dysfunctions in adulthood in a large sample. We analyzed baseline questionnaire data from Project SEXUS, a nationally representative cohort study on sexual health among 15- to 89-year-old Danish citizens. Our sample included sexually active participants aged ≥18 years who were queried about gender nonconformity in childhood or adolescence (N = 21 390). To capture sexual dysfunctions, we assessed (1) difficulties with lubrication, orgasm, vaginal cramps precluding sexual intercourse, and/or genital pain during partnered sexual activity in women and (2) difficulties with erection, premature ejaculation, orgasm, and/or genital pain during partnered sexual activity in men. Furthermore, we assessed whether such difficulties were perceived as problematic. The 6-item Female Sexual Function Index and the 5-item International Index of Erectile Function served as standardized measures. Polytomous logistic regression analyses yielded demographically weighted adjusted odds ratios (aORs) with 95% CIs for associations between childhood gender nonconformity and sexual dysfunctions, controlling for age, sociodemographics, health-related factors, and other potential confounders. Sexual difficulties and dysfunctions, as well as scores on the Female Sexual Function Index and International Index of Erectile Function. Age-adjusted odds ratios indicated that sexual dysfunctions were significantly more common among childhood gender-nonconforming than conforming participants. After controlling for additional potential confounders, most sexual dysfunctions-notably, vaginal cramps in women (aOR,2.12; 95% CI, 1.25-3.60) and genital pain dysfunction in men (aOR,2.99; 95% CI, 1.79-4.99)-remained significantly increased among childhood gender-nonconforming respondents. Findings suggest that self-perceived gender nonconformity in childhood or adolescence may negatively affect sexual functioning in adult life. If confirmed by future studies, they may warrant a clinical emphasis on such issues in sexologic treatment and care. Our study is the first to report associations between childhood gender nonconformity and adult sexual dysfunction, building on data from a large-scale, nationally representative cohort study. The retrospective assessment of childhood gender nonconformity via one item might have neglected significant dimensions of this construct. The present study is the first to show that individuals who recall being gender nonconforming in childhood or adolescence may be at a greater risk of experiencing sexual dysfunctions, particularly sexual pain disorders, as adults.

Following the children of depressed parents from childhood to adult life: A focus on mood and anxiety disorders.

Parental depression increases risk for anxiety and depression in offspring. The transition from adolescence to adulthood is a common risk period for onset of such disorders. However, relatively few studies have considered development of these disorders from childhood to adulthood including multiple assessments during this transition period. Offspring of depressed parents aged 9-17years at baseline were followed prospectively for 13years (n=337). Average length of follow-up was 16months between the first and second waves, 13months between the second and third, and 8years between the third and fourth. Current (3-month) psychopathology was assessed at each wave using diagnostic interviews. We derived estimates of 3-month prevalence, age at first diagnosis, course and comorbidity of disorders. Social functioning in adult life was assessed at the final wave and we assessed how prior and current disorder impacted adult functioning. A quarter of young people met criteria for a mood disorder and a third for anxiety disorder at least once. Mood and anxiety disorder prevalence increased from 4.5% and 15.8% respectively in childhood (9-11years) to 22.3% and 20.9% respectively by age 23-28. Increased prevalence across the transition from adolescence to adulthood was particularly marked in males, while prevalence increased earlier in adolescence in females. Age at first diagnosis varied widely (mood disordermean =16.5years (range 9-26); anxiety disorder mean=14.5years (range 9-28)). Over half (52%) reported functional impairment in early adulthood, 31% harmful alcohol use, and 10% self-harm or a suicide attempt. Both previous and current mood or anxiety disorder were associated with functional impairment in early adulthood. There is a prolonged risk period for mood and anxiety disorders in this group, with prevalence peaking in early adulthood. This highlights the need for prolonged vigilance and effective targeted interventions in the offspring of depressed parents.

Effect of maternal periconceptional undernutrition in sheep on cortisol regulation in offspring from mid-late gestation, through to adulthood.

Maternal periconceptional undernutrition (PCUN) alters fetal hypothalamic-pituitary-adrenal axis (HPAA) function and placental glucocorticoid metabolism in sheep. The effects of PCUN on HPAA function in adult life are not known. We investigated the effects of PCUN on fetal adrenal development across gestation and on cortisol regulation in adult offspring. Ewes were undernourished from 61 days before to 30 days after conception ('PCUN') or fed ad libitum ('N'). mRNA expression in the fetal adrenal gland of ACTH receptor (ACTHR), steroidogenic acute regulatory protein (STAR), cytochrome P450 17A1 (CYP17A1), 11beta-hydroxysteroid-dehydrogenase type 2 (11βHSD2), insulin-like growth factor-2 (IGF2), and in the fetal hippocampus of 11βHSD1, 11βHSD2, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) was determined at 50 (adrenal only), 85, 120 and 131 days of gestation (term=148 days). In adult offspring (≥ 3 years, N; 10 female, 5 male, PCUN; 10 female, 10 male) a combined arginine vasopressin (AVP, 0.1 μg/kg) and corticotropin-releasing hormone (CRH, 0.5 μg/kg) challenge and a metyrapone (40 mg/kg) challenge were undertaken. mRNA expression of ACTHR, STAR and CYP17A1 were determined in adult adrenals. Fetal adrenal STAR, CYP17A1 and IGF2 mRNA expression were not different between groups in early gestation but were higher in PCUN than N at 131 days' gestation (all p<0.01). PCUN reduced fetal hippocampal MR and GR mRNA expression by 50% at 85 day, but not in later gestation. Adult offspring plasma cortisol responses to AVP+CRH or metyrapone were not different between groups. Plasma ACTH response to AVP+CRH was lower in PCUN males but ACTH response to metyrapone was not different between groups. Adult adrenal ACTHR, STAR, and CYP17A1 mRNA expression were not affected by PCUN. We conclude that the effects of PCUN on fetal HPAA function that became apparent in late gestation, are not reflected in adrenal cortisol secretion in mid-adulthood.

Perinatal Taurine Supplementation Preserves the Benefits of Dynamic Exercise Training on Cardiovascular and Metabolic Functions and Prevents Organ Damage in Adult Male Exercised Rats.

Taurine supplementation is recommended during perinatal life to provide sufficient taurine for fetuses and newborns. Furthermore, perinatal taurine supplementation affects cardiovascular and metabolic functions in adult life. In adults, taurine supplementation is reported to improve exercise training. The present study explored the effects of perinatal taurine supplementation followed by dynamic exercise training on cardiovascular and metabolic functions in adult male rats. Pregnant Wistar rats were maintained on water containing or lacking 3% taurine from conception to weaning. After weaning, male offspring were fed normal rat chow and water throughout the study. At 4weeks of age, the taurine-treated and taurine-untreated rats were subjected to either a swimming exercise protocol (10-30 min a day, 5day a week) for 12weeks (Ex and TEx) or remained sedentary (C and T). At 16weeks of age, kidney weight, mean arterial pressure, baroreflex sensitivity, plasma leptin, plasma triglyceride, blood urea nitrogen, plasma creatinine, and SGOT were not significantly different among the four groups. Compared to the control, perinatal taurine supplementation alone did not significantly affect any of the measured cardiovascular and metabolic parameters. Exercise training significantly decreased bodyweight, heart rate, and visceral adipocyte size, irrespective of perinatal taurine supplementation, but increased SGPT and heart weight when compared to the control. However, the effect of exercise on SGPT, but not heart weight, was abolished by perinatal taurine supplementation. These data indicate that perinatal taurine supplementation not only preserves the beneficial effects of dynamic exercise training on cardiovascular and metabolic functions but also prevents exercise-induced organ damage in adult male rats.

Prenatal exposure to morphine impairs attention and impulsivity in adult rats.

An alarming number of neonates born with prenatal exposure to morphine has resulted from the opioid epidemic; however, the long-term effects of prenatal opioid exposure on offspring behavior remain relatively unknown. In this study, we evaluated whether prenatal exposure to the mu opioid receptor agonist, morphine, has enduring effects on cognitive functions in adult life. On embryonic days 11-18 (E11-E18), female pregnant rats were injected subcutaneously with either morphine or saline twice daily. Adult male offspring that was prenatally exposed to saline or morphine was trained in the 5-choice serial reaction time test (5-CSRTT) to test their cognitive abilities under baseline conditions. Next, these rats were treated with saline (1ml/kg), naloxone (1mg/kg), and acute morphine (1, 3, 5mg/kg), subcutaneously, once daily and following drug challenges rats were tested in the 5-CSRTT. Meanwhile, behavioral performance on training days between opioid drug challenges were analyzed to monitor possible drug-induced shifts in baseline performance. As a final experiment in order to investigate subchronic exposure to morphine, rats were injected with 5mg/kg morphine for 5days and then naloxone in the last day of the experiment (day 6). Firstly, during acquisition of a stable baseline in the training phase, rats prenatally exposed to morphine showed delayed learning of the task demands. Furthermore, under baseline responding the rats prenatally exposed to morphine showed declined inhibitory control demonstrated by increased impulsive and compulsive-like responding compared to rats prenatally exposed to saline. Moreover, acute and subchronic morphine challenges in the rats prenatally exposed to morphine caused a deficit in visuospatial attention in comparison with saline treatment as well as the rats prenatally exposed to saline. These effects were abolished by naloxone. The current findings indicate a direct causal effect of prenatal morphine exposure on inhibitory control and task learning later in life, as well as deficits in attention following morphine exposure in adulthood.

The “Slow Horse Racing Effect” on Lung Function in Adult Life in Chronic Obstructive Pulmonary Disease Associated to Biomass Exposure

Although different trajectories in lung function decline have been identified in patients with COPD associated to tobacco exposure (TE-COPD), genetic, environmental, and infectious factors affecting lung function throughout life have not been fully elucidated in patients with COPD associated to biomass (BE-COPD). In this review, we present current epidemiological findings and notable advances in the natural history of lung decline in BE-COPD, as well as conditions modeling the FEV1 trajectory, such as health insults, during the first years of childhood. Evidence shows that women exposed to biomass smoke reach adult life with a lower FEV1 than expected. However, in contrast to the “horse racing effect” predicting an excessive lung-function decline in forthcoming years, as observed in smokers, this decline is slower in non-smokers, and no rapid decliners are observed. Accordingly, BE-COPD might be considered another phenotype of COPD based on assessments of lung function decline. Likewise, other functional and clinical aspects described in this review suggest that this condition might be similar to TE-COPD. More research is needed to fully characterize this subgroup of variants of COPD.

Body mass index and weight change are associated with adult lung function trajectories: the prospective ECRHS study

BackgroundPrevious studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood...

The Influence of Attachment Styles and Personality Organization on Emotional Functioning After Childhood Trauma

Background: Current literature suggests a tenuous link among childhood trauma, personality organization, adult attachment, and emotional functioning in various psychiatric disorders. However, empirical research focusing on the interaction of these concepts is sparse. Therefore, this study intends to investigate the influence of personality organization and attachment dimensions on the relationship between childhood maltreatment and emotional functioning in adult life. To assess emotional functioning, we adopted the Affective Neuroscience model of primary emotions, comprising SEEKING, FEAR, ANGER, SADNESS, CARE, and PLAY.Methods: The total sample consisted of 616 nonclinical adults (Age: M = 30; SD = 9.53; 61.9% female). Path analysis was applied to investigate interactions among childhood trauma, personality organization, adult attachment, and primary emotion dispositions.Results: The findings suggest that childhood trauma significantly predicted deficits in personality organization and insecure attachment (all p < 0.001). Furthermore, a reduced level of personality organization was significantly associated with increased ANGER (p < 0.001), whereas adult attachment substantially predicted primary emotion dispositions in general. Moreover, the results indicate significant mediational effects of personality organization and attachment dimensions on the relationship between childhood trauma and primary emotions (p < 0.01). The final model was able to explain 48% of the variance in SADNESS, 38% in PLAY, 35% in FEAR, 28% in CARE, 14% in ANGER, and 13% in SEEKING.Discussion: The findings contribute to the understanding of the relationship between childhood maltreatment and impaired emotional functioning in adult life. Furthermore, the importance of personality organization and attachment dimensions for emotion regulation is underlined. Consequently, the treatment of patients with childhood trauma should focus on facilitating the development of more secure attachment patterns and increased personality functioning to improve overall emotional functioning.

Transcriptional Regulation of the Glutamate/GABA/Glutamine Cycle in Adult Glia Controls Motor Activity and Seizures in Drosophila.

The fruitfly Drosophila melanogaster has been extensively used as a genetic model for the maintenance of nervous system's functions. Glial cells are of utmost importance in regulating the neuronal functions in the adult organism and in the progression of neurological pathologies. Through a microRNA-based screen in adult Drosophila glia, we uncovered the essential role of a major glia developmental determinant, repo, in the adult fly. Here, we report that Repo expression is continuously required in adult glia to transcriptionally regulate the highly conserved function of neurotransmitter recycling in both males and females. Transient loss of Repo dramatically shortens fly lifespan, triggers motor deficits, and increases the sensibility to seizures, partly due to the impairment of the glutamate/GABA/glutamine cycle. Our findings highlight the pivotal role of transcriptional regulation of genes involved in the glutamate/GABA/glutamine cycle in glia to control neurotransmitter levels in neurons and their behavioral output. The mechanism identified here in Drosophila exemplifies how adult functions can be modulated at the transcriptional level and suggest an active synchronized regulation of genes involved in the same pathway. The process of neurotransmitter recycling is of essential importance in human epileptic and psychiatric disorders and our findings may thus have important consequences for the understanding of the role that transcriptional regulation of neurotransmitter recycling in astrocytes has in human disease.SIGNIFICANCE STATEMENT Glial cells are an essential support to neurons in adult life and have been involved in a number of neurological disorders. What controls the maintenance and modulation of glial functions in adult life is not fully characterized. Through a miR overexpression screen in adult glia in Drosophila, we identify an essential role in adult glia of repo, which directs glial differentiation during embryonic development. Repo levels modulate, via transcriptional regulation, the ability of glial cells to support neurons in the glutamate/GABA/glutamine cycle. This leads to significant abnormalities in motor behavior as assessed through a novel automated paradigm. Our work points to the importance of transcriptional regulation in adult glia for neurotransmitter recycling, a key process in several human neurological disorders.

Optimisation of birth weight and growth in the first 2 years favours an adult body composition which supports more physiological resting metabolic rates and cognitive function : Tanjungsari Cohort Study (TCS).

Resting metabolic rate and cognitive function may be associated with several factors, such as birth weight, growth, and fat-free mass in adulthood. The Tanjungsari Cohort Study (TCS) of 1988, to do with a maternal-child Risk Approach Strategy (RAS), provided the opportunity to determine the associations between birth weight, growth at 2 years, and body composition with adult resting metabolic rate and cognitive function. In 2009 some 197 and, in 2017,144 of these representative participants from the TCS were assessed for energy intake, anthropometry, body composition, indirect calorimetry, and cognitive function in relation to low (ALBW, n=66) or normal (ANBW, n=78) birth weight. Associations were adjusted for basic demographic data. Resting metabolic rate was positively associated with birth weight, body weight at 2 years of age, body mass index and fat free mass in adult life. Time to finish the Trail Making Test-A (TMT-A), a test of attention span, was significantly longer in the ALBW than the ANBW group (41.4±12.8 vs 37.8±15.6, p=0.005). In the ALBW group, weight catch-up improved TMT-A and logical memory test scores (29.5 vs 34.9.41, p=0.004; and 39.3 vs 29.4, p=0.04, respectively). Low birth weight was associated with poorer attention span in adult life; body weight gain at 2 years of age with better attention and memory function in adult life; a greater body mass index in adult life with better memory in adult life.

Comparison of clinical and cognitive characteristics of a Mexican adult clinical population with and without ADHD

Introduction. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting approximately 5% of the world population, with symptoms that may persist into adulthood. Despite the findings on the clinical course of this disorder, information regarding comorbidity patterns, psychosocial and executive functioning in adult life in those with and without ADHD in Latin American samples is scarce. Objective. The aim of this study is to compare the comorbidity pattern, psychosocial, and executive functioning of adults with and without ADHD from a clinical sample. Method. One hundred and fifty-one patients between 20 and 45 years, with screened positively on ASRS-V1.1, were invited to continue an evaluation process as part of clinical research program (PROMETEO): 1) K-SADS-PL Mx interview, 2) MINI-Plus interview, ASRS-V1-1 18 item version, BRIEF self-reported questionnaire, SCQA-ADHD, and 3) Individual case review by clinical expert in ADHD. Results. Individuals in the ADHD group had a higher average of comorbid disorders (2.5 SD 1.1 vs. 1.3 SD 1.0 respectively, F = .439; t = -6.621; df = 149; p &lt; .001), more likelihood of procrastinating (OR = 6.5; 95% CI[2.6, 16.2]; z = 4.0) and were more likely to present difficulties in both the behavior regulation index (OR = 104.9; 95% CI[31.8, 345.7]; z = 7.65) and the metacognitive index (OR = 94.79; 95% CI[29.10, 308.76]; z = 7.56) compared to the non-ADHD group, regardless of gender. Discussion and conclusions. Our results indicate that the ADHD adult group presented with more comorbidity, and worse psychosocial and executive functioning than non-ADHD adults.

Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats

Micronutrient malnutrition during intrauterine and postnatal growth may program cardiovascular diseases in adulthood. We examined whether moderate zinc restriction in male and female rats throughout fetal life, lactation and/or postweaning growth induces alterations that can predispose to the onset of vascular dysfunction in adulthood. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. After weaning, offspring were fed either a low- or a control zinc diet until 81 days. We evaluated systolic blood pressure (SBP), thoracic aorta morphology, nitric oxide (NO) system and vascular reactivity in 6- and/or 81-day-old offspring. At day 6, zinc-deficient male and female offspring showed a decrease in aortic NO synthase (NOS) activity accompanied by an increase in oxidative stress. Zinc-deficient 81-day-old male rats exhibited an increase in collagen deposition in tunica media, as well as lower activity of endothelial NOS (eNOS) that could not be reversed with an adequate zinc diet during postweaning life. Zinc deficiency programmed a reduction in eNOS protein expression and higher SBP only in males. Adult zinc-deficient rats of both sexes showed reduced vasodilator response dependent on eNOS activity and impaired aortic vasoconstrictor response to angiotensin-II associated with alterations in intracellular calcium mobilization. Female rats were less sensitive to the effects of zinc deficiency and exhibited higher eNOS activity and/or expression than males, without alterations in SBP or aortic histology. This work strengthens the importance of a balanced intake of micronutrients during perinatal growth to ensure adequate vascular function in adult life.

Splice-Switching Therapy for Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a genetic disorder with severity ranging from premature death in infants to restricted motor function in adult life. Despite the genetic cause of this disease being known for over twenty years, only recently has a therapy been approved to treat the most severe form of this disease. Here we discuss the genetic basis of SMA and the subsequent studies that led to the utilization of splice switching oligonucleotides to enhance production of SMN protein, which is absent in patients, through a mechanism of exon inclusion into the mature mRNA. Whilst approval of oligonucleotide-based therapies for SMA should be celebrated, we also discuss some of the limitations of this approach and alternate genetic strategies that are currently underway in clinical trials.

Beneficial Effects of Childhood Selective Dorsal Rhizotomy in Adulthood.

Background: Selective dorsal rhizotomy (SDR) has been used to treat children with spastic cerebral palsy (CP) for over three decades. However, little is known about the outcomes of childhood SDR in adults. Objectives: 1) To study the effects of childhood SDR on the quality of life and ambulatory function in adult life. 2) To determine late side effects of SDR in adults. Methods: Adults (> 17.9 years) who underwent SDR in childhood (2 - 17.9 years) between 1987 and 2013 were surveyed in 2015. Patients completed a survey, including questions on demographic information, quality of life, health, surgical outcomes, motor function, manual ability, pain, braces/orthotics, post-SDR treatment, living situation, education level, work status, and side effects of SDR. Results: In our study population of 294 patients (18.0 - 37.4 years), patients received SDR during the ages of 2.0 - 17.9 years and were followed up 2.2 to 28.3 years after surgery. Eighty-four percent had spastic diplegia, 12% had spastic quadriplegia, and 4% had spastic triplegia. The majority (88%) of patients reported improved post-SDR quality of life and 1% considered the surgery detrimental. Most (83%) would recommend the procedure to others and 3% would not. However, patients who would not recommend SDR to others ambulated with a walker or were not ambulatory at all prior to SDR. The majority (83%) of patients improved (30%) or remained stable (53%) in ambulation. Twenty-nine percent of patients reported pain, mostly in the back and lower limbs, with a mean pain level of 4.4 ± 2.4 on the Numeric Pain Rating Scale (NPRS). Decreased sensation in small areas of the lower limbs was reported by 8% of patients, though this did not affect daily life. Scoliosis was diagnosed in 28%, with 40% of these patients pursuing treatment. Whether scoliosis was related to SDR is not clear, though scoliosis is known to occur in patients with CP and also in the general population. Only 4% of patients underwent spinal fusion. Orthopedic surgeries were pursued by 59% of patients. The most common orthopedic surgeries were hamstring lengthenings (31%), Achilles tendon lengthenings (18%), adductor lengthenings (16%), and derotational osteotomies (16%). Twenty-four percent of all patients later underwent hip surgery and 8% had surgeries on their knees. Conclusion: Results of this study indicate that the beneficial effects of childhood SDR extend to adulthood quality of life and ambulatory function without late side effects of surgery.

Adult Body Height Is a Good Predictor of Different Dimensions of Cognitive Function in Aged Individuals: A Cross-Sectional Study.

Background: Adult height, weight, and adiposity measures have been suggested by some studies to be predictors of depression, cognitive impairment, and dementia. However, the presence of confounding factors and the lack of a thorough neuropsychological evaluation in many of these studies have precluded a definitive conclusion about the influence of anthropometric measures in cognition and depression. In this study we aimed to assess the value of height, weight, and abdominal perimeter to predict cognitive impairment and depressive symptoms in aged individuals.Methods and Findings: Cross-sectional study performed between 2010 and 2012 in the Portuguese general community. A total of 1050 participants were included in the study and randomly selected from local area health authority registries. The cohort was representative of the general Portuguese population with respect to age (above 50 years of age) and gender. Cognitive function was assessed using a battery of tests grouped in two dimensions: general executive function and memory. Two-step hierarchical multiple linear regression models were conducted to determine the predictive value of anthropometric measures in cognitive performance and mood before and after correction for possible confounding factors (gender, age, school years, physical activity, alcohol consumption, and smoking habits). We found single associations of weight, height, body mass index, abdominal perimeter, and age with executive function, memory and depressive symptoms. However, when included in a predictive model adjusted for gender, age, school years, and lifestyle factors only height prevailed as a significant predictor of general executive function (β = 0.139; p < 0.001) and memory (β = 0.099; p < 0.05). No relation was found between mood and any of the anthropometric measures studied.Conclusions and Relevance: Height is an independent predictor of cognitive function in late-life and its effects on the general and executive function and memory are independent of age, weight, education level, gender, and lifestyle factors. Altogether, our data suggests that modulators of adult height during childhood may irreversibly contribute to cognitive function in adult life and that height should be used in models to predict cognitive performance.

Does skeletal muscle have an 'epi'-memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise.

SummarySkeletal muscle mass, quality and adaptability are fundamental in promoting muscle performance, maintaining metabolic function and supporting longevity and healthspan. Skeletal muscle is programmable and can ‘remember’ early‐life metabolic stimuli affecting its function in adult life. In this review, the authors pose the question as to whether skeletal muscle has an ‘epi’‐memory? Following an initial encounter with an environmental stimulus, we discuss the underlying molecular and epigenetic mechanisms enabling skeletal muscle to adapt, should it re‐encounter the stimulus in later life. We also define skeletal muscle memory and outline the scientific literature contributing to this field. Furthermore, we review the evidence for early‐life nutrient stress and low birth weight in animals and human cohort studies, respectively, and discuss the underlying molecular mechanisms culminating in skeletal muscle dysfunction, metabolic disease and loss of skeletal muscle mass across the lifespan. We also summarize and discuss studies that isolate muscle stem cells from different environmental niches in vivo (physically active, diabetic, cachectic, aged) and how they reportedly remember this environment once isolated in vitro. Finally, we will outline the molecular and epigenetic mechanisms underlying skeletal muscle memory and review the epigenetic regulation of exercise‐induced skeletal muscle adaptation, highlighting exercise interventions as suitable models to investigate skeletal muscle memory in humans. We believe that understanding the ‘epi’‐memory of skeletal muscle will enable the next generation of targeted therapies to promote muscle growth and reduce muscle loss to enable healthy aging.

Maternal protein restriction during gestation impairs female offspring pancreas development in the rat

A maternal low-protein (LP) diet programs fetal pancreatic islet β-cell development and function and predisposes offspring to metabolic dysfunction later in life. We hypothesized that maternal protein restriction during pregnancy differentially alters β- and α-cell populations in offspring by modifying islet ontogeny and function throughout life. We aimed to investigate the effect of an LP maternal diet on pancreatic islet morphology and cellular composition in female offspring on postnatal days (PNDs) 7, 14, 21, 36, and 110. Mothers were divided into 2 groups: during pregnancy, the control group (C) was fed a diet containing 20% casein, and the LP group was fed an isocaloric diet with 10% casein. Offspring pancreases were obtained at each PND and then processed. β and α cells were detected by immunohistochemistry, and cellular area and islet size were quantified. Islet cytoarchitecture and total area were similar in C and LP offspring at all ages studied. At the early ages (PNDs 7-21), the proportion of β cells was lower in LP than C offspring. The proportion of α cells was lower in LP than C offspring on PND 14 and higher on PND 21. The β/α-cell ratio was lower in LP compared with C offspring on PNDs 7 and 21 and higher on PND 36 (being similar on PNDs 14 and 110). We concluded that maternal protein restriction during pregnancy modifies offspring islet cell ontogeny by altering the proportions of islet sizes and by reducing the number of β cells postnatally, which may impact pancreatic function in adult life.

Postnatal overnutrition programs the thyroid hormone metabolism and function in adulthood.

Early overnutrition (EO) during lactation leads to obesity, leptin resistance and lower thyroid hormone (TH) levels during adulthood. To better understand the biological significance of this thyroid hypofunction, we studied the long-term effects of postnatal EO on both the function of hypothalamic-pituitary-thyroid (HPT) axis and the metabolism and action of TH. To induce EO, the litter size was reduced to three pups per litter (small litter (SL) group) on the third day of lactation. In the controls (normal litter group), litter size was adjusted to 10 pups per litter. Rats were killed at PN180. TRH content and in vitro TSH were evaluated. Iodothyronine deiodinase (D1 and D2) activities were measured in different tissues. Mitochondrial α-glycerol-3-phosphate dehydrogenase (mGPD), uncoupling protein 1 (UCP1) and TH receptor (TRβ1) were evaluated to assess TH action. The SL group presented lower TRH, intra-pituitary and released TSH levels, despite unchanged plasma TSH. They presented lower D1 activity in thyroid, muscle and white adipose tissue (WAT) and higher D2 activity in the hypothalamus, pituitary, brown adipose tissue (BAT) and WAT, which confirmed the hypothyroidism. UCP1 in BAT and TRβ1 in WAT were decreased, which can contribute to a lower catabolic status. Despite the lower TH, the D2 activity in the thyroid, heart and testes was unchanged. Hepatic D1, mGPD and TRβ1 were also unchanged in SL rats, suggesting that the TH conversion and action were preserved in the liver, even with lower TH. Thus, this model indicates that postnatal EO changes thyroid function in adult life in a tissue-specific way, which can help in the understanding of obesogenesis.