Age and sex-dependent gut alterations in mice induced by neonatal immune activation with lipopolysaccharide.

Neonatal immune activation (NIA) through exposure to lipopolysaccharide (LPS) induces adult behavioral changes in rodents that resemble symptoms of developmental disorders, such as autism spectrum disorder. The neonatal timing of LPS exposure appears to play a crucial role in determining the nature and extent of long-term changes. This study aims to explore whether a 3-day LPS-NIA triggers sex- and age-related changes in gut function, potentially linking LPS-NIA to gastrointestinal dysfunction. Male and female Swiss mice received intraperitoneal injections of LPS or saline on postnatal days (PN) 3, 5, and 7. At PN35 (juvenile) and PN70 (adult), gut inflammation and oxidative stress were evaluated in addition to assessments of working memory, depressive-like symptoms, sociability, and repetitive behavior. Gut examination showed elevated C-X-C motif chemokine receptor 3 (CXCR3) in LPS-NIA mice, while MyD88 and Zonulin expressions were significantly higher only in adult LPS-NIA females. Interleukin (IL)-23 expression increased in juvenile and adult male and juvenile female LPS-NIA mice. Oxidative changes included decreased duodenal reduced glutathione (GSH) in juvenile females and ileal GSH in adult females exposed to LPS-NIA. Regarding behavioral alterations, adult LPS-NIA females exhibited depressive-like behavior. Working memory deficits were observed across all LPS-NIA groups. Only juvenile LPS-NIA females increased grooming, while rearing was higher in adult LPS-NIA mice of both sexes. The findings imply that LPS-NIA impacts intestinal barrier function and causes gut inflammatory alterations that are sex- and age-specific. These findings pave the way for exploring potential mechanisms that could contribute to LPS-induced gastrointestinal disturbances among individuals with ASD.

Central and peripheral mechanisms underlying respiratory deficits in a mouse model of accelerated senescence.

Aging invariably decreases sensory and motor stimuli and affects several neuronal systems and their connectivity to key brain regions, including those involved in breathing. Nevertheless, further investigation is needed to fully comprehend the link between senescence and respiratory function. Here, we investigate whether a mouse model of accelerated senescence could develop central and peripheral respiratory abnormalities. Adult male Senescence Accelerated Mouse Prone 8 (SAMP8) and the control SAMR1 mice (10 months old) were used. Ventilatory parameters were assessed by whole-body plethysmography, and measurements of respiratory input impedance were performed. SAMP8 mice exhibited a reduction in the density of neurokinin-1 receptor immunoreactivity in the entire ventral respiratory column. Physiological experiments showed that SAMP8 mice exhibited a decreased tachypneic response to hypoxia (FiO2 = 0.08; 10 min) or hypercapnia (FiCO2 = 0.07; 10 min). Additionally, the ventilatory response to hypercapnia increased further due to higher tidal volume. Measurements of respiratory mechanics in SAMP8 mice showed decreased static compliance (Cstat), inspiratory capacity (IC), resistance (Rn), and elastance (H) at different ages (3, 6, and 10 months old). SAMP8 mice also have a decrease in contractile response to methacholine compared to SAMR1. In conclusion, our findings indicate that SAMP8 mice display a loss of the NK1-expressing neurons in the respiratory brainstem centers, along with impairments in both central and peripheral respiratory mechanisms. These observations suggest a potential impact on breathing in a senescence animal model.

Age-, region-, and day/night-related variation of the chloride reversal potential in the rat suprachiasmatic nucleus.

The master control of mammalian circadian rhythms is the suprachiasmatic nucleus (SCN), which is formed by the ventral and dorsal regions. In SCN neurons, GABA has an important function and even excitatory actions in adulthood. However, the physiological role of this neurotransmitter in the developing SCN is unknown. Here, we recorded GABAergic postsynaptic currents (in the perforated-patch configuration using gramicidin) to determine the chloride reversal potential (ECl) and also assessed the immunological expression of the Na-K-Cl cotransporter 1 (NKCC1) at early ages of the rat (postnatal days (P) 3 to 25), during the day and night, in the two SCN regions. We detected that ECl greatly varied with age and depending on the SCN region and time of day. Broadly speaking, ECl was more hyperpolarized with age, except for the oldest age studied (P20-25) in both day and night in the ventral SCN, where it was less negative. Likewise, ECl was more hyperpolarized in the dorsal SCN both during the day and at night; while ECl was more negative at night both in the ventral and the dorsal SCN. Moreover, the total NKCC1 fluorescent expression was higher during the day than at night. These results imply that NKCC1 regulates the circadian and developmental fluctuations in the [Cl-]i to fine-tune ECl, which is crucial for either excitatory or inhibitory GABAergic actions to occur in the SCN.

Association of Moderate and Vigorous Physical Activity With Cognitive Performance: Evidence From Brazil.

OBJECTIVE: It is estimated that 2% of dementia cases worldwide could be prevented with increases in physical activity. However, there is little evidence of the association between vigorous physical activity (VPA) and cognitive performance. This study aimed to investigate the association of moderate physical activity (MPA) and VPA with cognitive performance in older adults from the Brazilian Longitudinal Study of Aging (ELSI-Brasil). PATIENTS AND METHODS: Data from 7954 participants were analyzed. Mean age was 61.8 ± 9.2 years, 61.8% were women, and 44.3% were mixed races. Cognitive performance evaluated the memory, temporal orientation, and verbal fluency domains. A global composite z-score was derived from the tests. Physical activity was assessed by self-report. We used linear regression models to verify the association of MPA and VPA with cognitive performance. RESULTS: Compared with participants who did not meet the guidelines for MPA (<150 min/wk), those who met the guidelines (150 to 299 min/wk) and those who performed more than 2x the recommended amount of MPA (300 min or more/wk) had better global cognitive performance (ß = 0.163, 95% CI = 0.086, 0.241; P < 0.001; ß = 0.180, 95% CI = 0.107, 0.253, P < 0.001, respectively). We found no association between VPA and cognitive performance. CONCLUSION: There was no additional benefit of VPA for cognitive performance.

Glutamatergic Neurotransmission in Aging and Neurodegenerative Diseases: A Potential Target to Improve Cognitive Impairment in Aging.

Aging is characterized by the decline in many of the individual's capabilities. It has been recognized that the brain undergoes structural and functional changes during aging that are occasionally associated with the development of neurodegenerative diseases. In this sense, altered glutamatergic neurotransmission, which involves the release, binding, reuptake, and degradation of glutamate (Glu) in the brain, has been widely studied in physiological and pathophysiological aging. In particular, changes in glutamatergic neurotransmission are exacerbated during neurodegenerative diseases and are associated with cognitive impairment, characterized by difficulties in memory, learning, concentration, and decision-making. Thus, in the present manuscript, we aim to highlight the relevance of glutamatergic neurotransmission during cognitive impairment to develop novel strategies to prevent, ameliorate, or delay cognitive decline. To achieve this goal, we provide a comprehensive review of the changes reported in glutamatergic neurotransmission components, such as Glu transporters and receptors during physiological aging and in the most studied neurodegenerative diseases. Finally, we describe the current therapeutic strategies developed to target glutamatergic neurotransmission.

Physical Performance and Telomere Length in Older Adults.

BACKGROUND: The aging population prompts studying risk factors and markers to predict healthy aging. Telomere length is a promising candidate for assessing various age-related traits. AIM OF THE STUDY: To investigate the association between physical performance and telomere length. METHODS: We enrolled 323 older Mexican adults from the "Cohort of Obesity, Sarcopenia, and Frailty of Older Mexican Adults" affiliated with the Instituto Mexicano del Seguro Social and assessed their physical performance using the Short Physical Performance Battery, dividing participants into low (≤7) and high (>7) groups. Absolute telomere length was determined by qPCR, and individuals were classified into short (≤4.22 kb) and long (>4.22 kb) groups. We calculated the mean and adjusted mean, considering sex and age, among others, with 95% CI. We estimated the effect size between physical performance and telomere length using Cohen's d for unequal group sizes and calculated the odds ratio for physical performance based on telomere length. RESULTS: Participants with low physical performance had significantly shorter telomeres (mean 4.14.44.7 kb, adjusted mean 3.54.04.5 kb, p <0.001), while those with high physical performance exhibited longer telomeres (mean 5.55.75.9 kb, adjusted mean 4.75.35.8 kb, p <0.001), with a medium-to-high telomere length effect size (d = 0.762). The odds of low physical activity increased 2.13.66.1-fold per kb of telomere attrition (adjOR 1.73.36.3, p <0.001). CONCLUSION: Decreased physical function is associated with shorter telomere length. Absolute telomere length presents a promising biomarker for distinguishing between healthy and unhealthy aging, warranting further investigation.

The role of interleukin-10 in mitigating endoplasmic reticulum stress in aged mice through exercise.

Although unfolded protein response (UPR) is essential for cellular protection, its prolonged activation may induce apoptosis, compromising cellular longevity. The aging process increases the endoplasmic reticulum (ER) stress in skeletal muscle. However, whether combined exercise can prevent age-induced ER stress in skeletal muscle remains unknown. Evidence suggests that ER stress may increase inflammation by counteracting the positive effects of interleukin-10 (IL-10), whereas its administration in cells inhibits ER stress and apoptosis. This study verified the effects of aging and combined exercise on physical performance, ER stress markers, and inflammation in the quadriceps of mice. Moreover, we verified the effects of IL-10 on ER stress markers. C57BL/6 mice were distributed into young (Y, 6 mo old), old sedentary (OS, sedentary, 24 mo old), and old trained group (OT, submitted to short-term combined exercise, 24 mo old). To clarify the role of IL-10 in UPR pathways, knockout mice lacking IL-10 were used. The OS mice presented worse physical performance and higher ER stress-related proteins, such as C/EBP homologous protein (CHOP) and phospho-eukaryotic translation initiation factor 2 alpha (p-eIF2α/eIF2α). The exercise protocol increased muscle strength and IL-10 protein levels in OT while inducing the downregulation of CHOP protein levels compared with OS. Furthermore, mice lacking IL-10 increased BiP, CHOP, and p-eIF2α/eIF2α protein levels, indicating this cytokine can regulate the ER stress response in skeletal muscle. Bioinformatics analysis showed that endurance and resistance training downregulated DNA damage inducible transcript 3 (DDIT3) and XBP1 gene expression in the vastus lateralis of older people, reinforcing our findings. Thus, combined exercise is a potential therapeutic intervention for promoting adjustments in ER stress markers in aged skeletal muscle.NEW & NOTEWORTHY Aging elevates endoplasmic reticulum (ER) stress in skeletal muscle, potentially heightening inflammation by opposing interleukin-10 (IL-10) effects. This study found that short-term combined exercise boosted strength and IL-10 protein levels while reducing CHOP protein levels in older mice. In addition, IL-10-deficient mice exhibited increased ER stress markers, highlighting IL-10's role in regulating ER stress in skeletal muscle. Consequently, combined exercise emerges as a therapeutic intervention to elevate IL-10 and adjust ER stress markers in aging.

Updates in inspiratory muscle training for older adults: A systematic review.

Systematic reviews support the benefits of inspiratory muscle training (IMT) for exercise performance. Recently, many health benefits from IMT have been reported in older adults. Therefore, this work reviewed the literature focusing on IMT effects beyond physical performance in older adults, such as cardiorespiratory, metabolic, and postural balance outcomes. Searches were conducted with the following terms: ("respiratory muscle training" OR "inspiratory muscle training") OR ("inspiratory muscle strength training") AND ("elderly" OR "older" OR "aging" OR "aging"), and using the databases: MEDLINE (PubMed), SCOPUS and EUROPE PMC. Of the 356 articles found, 13 matched the inclusion criteria after screening. Based on reviewed studies, four to eight weeks of IMT (Mostly from 50 % up to 75 % of MIP, 7 days/week) improve cardiac autonomic control at rest and post-exercise, cerebrovascular response to orthostatic stress, static and dynamic balance, blood pressure control, endothelial function, and oxidative stress in older adults. The benefits of IMT in cardiac autonomic and vascular functions are reversed after training cessation. It thus appears that IMT promotes broad physiological gains for the older population. It is necessary to carry out more randomized clinical trials on the subject to confirm the findings of this research.

Social relationships and their association with the functional capacity of older Chilean adults: longitudinal evidence.

BACKGROUND: Functional capacity is recognized as a central factor for health in old age and not all studies that seek to clarify the role of social relationships in functional capacity are conclusive. The subject has only been studied in a limited way in Latin America, a region that is aging prematurely, with evidence primarily from developed countries, which have experienced a more gradual aging of their population. This longitudinal study aimed to determine how aspects of social relationships impact the functionality of older Chileans. METHODOLOGY: We conducted a cohort study of 2,265 people aged 60 years or older who lived in the community and resided in Greater Santiago, Chile. Five aspects of social relationships were considered at baseline (participation in groups, clubs, or organizations; number of people in the household; participation in recreational activities; perception of material support, help or advice, and marital status), from which a cluster analysis by conglomerate was performed and used as the exposure of interest. Functional limitation (FL) was the dependent variable, classified as a limitation in at least 1 basic activity of daily living or 1 instrumental activity or 2 advanced activities. The control variables considered were: sex, age, educational level, multimorbidity, depression and years of follow-up. Survival analyses using a Cox proportional hazard regression and multilevel logistic regressions (person level and follow-up wave level) were performed. RESULTS: The identified clusters were four: "without social participation and does not live alone"; "without a partner and without social participation"; "no perception of support and no social participation"; "with participation, partner and perception of support". Social relationship clusters predicted FL incidence and FL reporting during follow-up. Being in the clusters "without social participation and does not live alone" and "without partner and without social participation" were risk factors for incident FL and report of FL during follow-up, compared to being in the reference cluster "with participation, partner and perception of support. CONCLUSIONS: In summary, our study showed that participating in social organizations, not living alone and having a partner are protective factors for presenting and developing functional limitation in old age for community-living Chileans in an urban area.

Physical Exercise Inhibits Cognitive Impairment and Memory Loss in Aged Mice, and Enhances Pre- and Post-Synaptic Proteins in the Hippocampus of Young and Aged Mice.

The aim of this study was to evaluate the effects of swimming in the brain and behavior of young and aged mice. Forty-eight male C57BL/6 J mice were randomly distributed into 4 groups (n = 12 per group, 3 and 18 months old). The subdivision of the groups was: 3 months-SED, 18 months-SED, 3 months-EXE, and 18 months-EXE. SED mice did not swim, while EXE mice performed the physical exercise protocol. Training was initiated 48 h after the adaptation week. Swimming sessions consisted of 30 min, with no overload, 5 days per week, for 4 weeks. After the exercise protocol, it was revealed working and spatial memory were impaired in the 18 months-SED group. Pre- and post-synaptic proteins were enhanced in the groups that swam when compared to the 3- and 8 months-SED groups. Lipid peroxidation was greater in the aged mice that did not perform the physical exercise protocol and might have contributed to the cognitive impairment in this group. In conclusion, an aerobic physical exercise protocol, performed through regular swimming sessions, inhibited cognitive impairment, memory loss and lipid peroxidation in the aged mice, while pre- and post-synaptic proteins were enhanced in the hippocampus of young and aged mice.

Cell Proliferation and Apoptosis-Key Players in the Lung Aging Process.

Currently, the global lifespan has increased, resulting in a higher proportion of the population over 65 years. Changes that occur in the lung during aging increase the risk of developing acute and chronic lung diseases, such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung cancer. During normal tissue homeostasis, cell proliferation and apoptosis create a dynamic balance that constitutes the physiological cell turnover. In basal conditions, the lungs have a low rate of cell turnover compared to other organs. During aging, changes in the rate of cell turnover in the lung are observed. In this work, we review the literature that evaluates the role of molecules involved in cell proliferation and apoptosis in lung aging and in the development of age-related lung diseases. The list of molecules that regulate cell proliferation, apoptosis, or both processes in lung aging includes TNC, FOXM1, DNA-PKcs, MicroRNAs, BCL-W, BCL-XL, TCF21, p16, NOX4, NRF2, MDM4, RPIA, DHEA, and MMP28. However, despite the studies carried out to date, the complete signaling pathways that regulate cell turnover in lung aging are still unknown. More research is needed to understand the changes that lead to the development of age-related lung diseases.

Tissue desaturation is not a major determinant of aging-related impairment in skeletal muscle reactive hyperemia: a retrospective analysis.

Near-infrared spectroscopy combined with vascular occlusion test (NIRS-VOT) is a reactive hyperemia technique for in vivo evaluation of skeletal muscle microvascular reactivity. Previous studies using NIRS-VOT have been shown to be able to detect impairments in microvascular function in high-risk cardiovascular disease populations, such as older individuals. It has been demonstrated that older individuals have slower reactive hyperemia compared with young individuals. Importantly, older individuals also show less desaturation during ischemia compared with young individuals. Based on these findings, it has been suggested that the slower reactive hyperemia observed in older individuals is explained by the lower desaturation during blood flow occlusion (reduced ischemic stimulus). This retrospective analysis compared reactive hyperemia in 36 young and 47 older tissue desaturation-matched individuals that underwent 5-min blood flow occlusion. Overall, we showed that older individuals have impaired reactive hyperemia compared with young when matching for the degree of desaturation and blood flow occlusion time. These findings provide evidence that lower tissue desaturation during ischemia is not a major determinant of impaired reactive hyperemia in older individuals.NEW & NOTEWORTHY Previous findings have suggested that aging-related impairment in skeletal muscle reactive hyperemia is majorly influenced by a lower degree of tissue desaturation during ischemia in older individuals compared with young individuals. In a retrospective analysis including 83 tissue desaturation-matched individuals, we show that the degree of tissue desaturation is not a major determinant of aging-related impairments in reactive hyperemia.

Neuronal Stability, Volumetric Changes, and Decrease in GFAP Expression of Marmoset (Callithrix jacchus) Subcortical Visual Nuclei During Aging.

The physiological aging process is well known for functional decline in visual abilities. Among the components of the visual system, the dorsal lateral geniculate nucleus (DLG) and superior colliculus (SC) provide a good model for aging investigations, as these structures constitute the main visual pathways for retinal inputs reaching the visual cortex. However, there are limited data available on quantitative morphological and neurochemical aspects in DLG and SC across lifespan. Here, we used optical density to determine immunoexpression of glial fibrillary acidic protein (GFAP) and design-based stereological probes to estimate the neuronal number, total volume, and layer volume of the DLG and SC in marmosets (Callithrix jacchus), ranging from 36 to 143 months of age. Our results revealed an age-related increase in total volume and layer volume of the DLG, with an overall stability in SC volume. Furthermore, a stable neuronal number was demonstrated in DLG and superficial layers of SC (SCv). A decrease in GFAP immunoexpression was observed in both visual centers. The results indicate region-specific variability in volumetric parameter, possibly attributed to structural plastic events in response to inflammation and compensatory mechanisms at the cellular and subcellular level. Additionally, the DLG and SCv seem to be less vulnerable to aging effects in terms of neuronal number. The neuropeptidergic data suggest that reduced GFAP expression may reflect morphological atrophy in the astroglial cells. This study contributes to updating the current understanding of aging effects in the visual system and stablishes a crucial foundation for future research on visual perception throughout the aging process.

Relationship between aging and excess body fat with markers of inflammation, skeletal muscle mass and strength in Mexican community-dwelling people.

INTRODUCTION: Aging is accompanied by changes in body composition, such as an increase in fat mass (FM), a decrease in skeletal muscle mass index (SMMI) and muscle strength, combined with a chronic inflammatory process (CI). OBJECTIVE: Determine the relationship between age and excess body fat with markers of chronic inflammation, skeletal muscle mass and strength. METHODS: A cross-sectional alitical study was carried out in a convenience sample of adults 45 to 59 years old (n = 100) and older adults 60 to 74 years old (n = 133). All participants had their body composition measured with an impedance meter. They were subsequently divided into two groups: (i) with excess fat (WEF), (ii) without excess fat (NEF), in order to relate excess fat and age with inflammation, muscle mass and strength. RESULTS: NEF adults and older adults had similar values of SMMI (9.1 ± 1.5 vs. 8.8 ± 1.3, p > 0.05) and strength (28 ± 8 vs. 27 ± 8.6, p > 0.05). Likewise, WEF adults showed significantly lower values than NEF adults in the SMMI (7.9 ± 0.8 vs. 9.1 ± 1.5, p < 0.05) and strength (28 ± 8 vs. 22 ± 5, p < 0.001). Also, WEF older adults presented significantly lower values in the SMMI (15.9 ± 1.8 vs. 22.8 ± 5.1, p < 0.05) and strength (17.9 ± 4.8 vs. 27 ± 8.6, p < 0.001). CONCLUSIONS: Our findings suggest that excess fat mass is a risk factor that has a significantly greater influence than aging per se on the index of skeletal muscle mass and strength.

Cognition, physical function, and life purpose in the rural elderly population: A systematic review protocol.

INTRODUCTION: Aging in rural settings worldwide, from the perspective of cognition, physical function, and life purpose essential constructs for a prosperous old age, still needs comprehensive discussion. This systematic review protocol aims to highlight the prevalence of cognitive decline, physical functioning, and life purpose in older adults aging in rural community settings. METHODS AND ANALYSIS: We will include cross-sectional studies published until April 2023 found in 8 databases: Embase, MEDLINE, LILACS, PsycINFO, Scopus, SciELO, and Web of Science. Ryyan software will be used for the first selection, and the Observational Study Quality Evaluation (OSQE) will assess methodological quality and risk of bias. Primary analysis will involve titles and abstracts using MeSH descriptors such as "Physical functioning," "Cognition," "Cognitive function," "Life purpose," "Elderly," "Older," "Rural aging," "Rural population," "Communities, rural," "Distribution, rural spatial," "Medium communities," "Rural settlement," "Small community." If necessary, secondary analysis will include a complete reading of selected articles by two blinded reviewers, confirmed by a third person. Publication bias will be assessed using cross-sectional analytical study quality. Sensitivity analyses will identify manuscripts significantly influencing combined prevalence of endpoints.

Impact of aging on maximal oxygen uptake in female runners and sedentary controls.

The present study aimed to compare V̇O2max (absolute, adjusted to total body mass, and adjusted to lean mass) in recreational runners and sedentary women < and > 50 yr and verify the effect of aging and physical activity level on the three types of V̇O2 max expression. The study included 147 women:85 runners (45.7 ± 14.1 yr) and 62 sedentary controls (48.8 ± 9.8 yr). They were subjected to cardiopulmonary exercise testing for V̇O2 max measurement and a body composition test by dual-emission X-ray absorptiometry system. V̇O2max were expressed as absolute values (L/min), relative to total body mass values (mL/kg/min), and relative to lean mass values (mL/kgLM/min). The two-way analysis of variance revealed a significant interaction [F(2,131) = 4.43, p < 0.001] and effects of age group [F(2,131) = 32.79, p < 0.001] and physical activity group [F(2,131) = 55.64, p < 0.001] on V̇O2max (mL/min). V̇O2max (mL/kg/min) and V̇O2 max (mL/kgLM/min) were significantly influenced by age and physical activity levels. The multiple regression model explains 76.2 % of the dependent variable V̇O2max (mL/kg/min), age (ß = -0.335, t = -7.841, p < 0.001), and physical activity group (ß = -0.784, t = -18.351, p < 0.001). In conclusion, female runners had higher V̇O2 max values than sedentary women at all ages, even though aging has a greater impact on V̇O2 max in the runners group. In addition to cardiorespiratory fitness, women's metabolic lean mass function, as measured by V̇O2max adjusted by lean mass, is significantly influenced by aging. Finally, physical activity has a greater impact on V̇O2 max levels than aging.

Ketogenic diet administration later in life improves memory by modifying the synaptic cortical proteome via the PKA signaling pathway in aging mice.

Aging compromises brain function leading to cognitive decline. A cyclic ketogenic diet (KD) improves memory in aged mice after long-term administration; however, short-term effects later in life and the molecular mechanisms that govern such changes remain unclear. Here, we explore the impact of a short-term KD treatment starting at elderly stage on brain function of aged mice. Behavioral testing and long-term potentiation (LTP) recordings reveal that KD improves working memory and hippocampal LTP. Furthermore, the synaptosome proteome of aged mice fed a KD long-term evidence changes predominantly at the presynaptic compartment associated to the protein kinase A (PKA) signaling pathway. These findings were corroborated in vivo by western blot analysis, with high BDNF abundance and PKA substrate phosphorylation. Overall, we show that a KD modifies brain function even when it is administered later in life and recapitulates molecular features of long-term administration, including the PKA signaling pathway, thus promoting synaptic plasticity at advanced age.

Allostatic load measures in older adults with subjective cognitive decline and mild cognitive impairment: A cross-sectional analysis from the Brazilian Memory and Aging Study.

INTRODUCTION: An increasing body of research suggests that stress and allostatic load are related to cognitive dysfunction and neurodegeneration. OBJECTIVES: to determine the relationship between allostatic load (AL) and cognitive status in older adults classified with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODOLOGY: Using the Brazilian Memory and Aging Study (BRAMS) database, we analyzed data from 57 older adults with SCD and MCI. Blood neuroendocrine (cortisol, DHEA-s), inflammatory (C-reactive protein, fibrinogen), metabolic (HbA1c, HDL-cholesterol, total cholesterol, creatinine), and cardiovascular (blood pressure, waist/hip ratio) were transformed into an AL index. RESULTS: Despite a significant difference in the univariate analysis between waist/hip ratio (0.94 in the MCI group vs. 0, 88 in the SCD group, p = 0.03), total cholesterol levels (194 vs. 160, p = 0.02), and AL index (36.9 % in the MCI group vs. 27.2 % in the SCD group, p = 0.04), AL was not associated with SCD or MCI in the multivariate analysis. CONCLUSION: Our data suggest that different profiles of AL in MCI compared to individuals with SCD could be due to cofounding factors. These findings need to be confirmed in longitudinal studies investigating profiles of AL changes at preclinical and prodromal stages of Alzheimer's disease.

Accumulated HIIT inhibits anxiety and depression, improves cognitive function, and memory-related proteins in the hippocampus of aged rats.

This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15 min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15 min, while the 3xHIIT performed three daily sessions of 5 min with a 4 h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO2max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats.