Long-term calorie restriction prevented memory impairment in middle-aged male mice and increased a marker of DNA oxidative stress in hippocampal dentate gyrus.

Calorie restriction (CR) is a non-invasive and economic approachknown to increase healthspan and life expectancy, through a decrease in oxidative stress, an increase in neurotrophins, among other benefits. However, it is not clear whether its benefit could be noted earlier, as at the beginning of middle-age. Hence, weaimed to determine whether six months of long-term CR, from early adulthood to the beginning of middle age (10 months of age) could positively affect cognitive, neurochemical, and behavioral parameters. Male C57BL6/J mice were randomly distributed into Young Control (YC, ad libitum food), Old Control (OC, ad libitum food), and Old Restricted (OR, 30 % of caloric restriction) groups. To analyze the cognitive and behavioral aspects, the novel object recognition task (NOR), open field, and elevated plus maze tests were performed. In addition, immunohistochemistry targetingΔFosB (neuronal activity), brain-derived neurotrophic factor (BDNF) and the DNA oxidative damage (8OHdG) in hippocampal subfields CA1, CA2, CA3, and dentate gyrus (DG), and in basolateral amygdala and striatum were performed. Our results showed that long-term CR prevented short-term memory impairment related to aging and increased 8OHdG in hippocampal DG. BDNF was not involved in the effects of either age or CR on memory at middle-age, as it increased in CA3 of the OC group but was not altered in OR. Regarding anxiety-type behavior, no parameter showed differences between the groups. In conclusion, while the effects of long-term CR on anxiety-type behavior were inconclusive, it mitigated the memory deficit related to aging, which was accompanied by an increase in hippocampal 8OHdG in DG. Future studies should investigate whether the benefits of CR would remain if the restriction were interrupted after this long-term protocol.

The Differential Effect of Schooling and Physical Activity on Dementia in Older Women and Men from Brazil: Implications for Policymaking.

BACKGROUND: Modifiable risk factors exert crucial impact on dementia. OBJECTIVE: We sought to answer the question: do two modifiable risk factors, schooling level and physical activity (PA), affect cognitive function similarly in each sex? METHODS: This cross-sectional study was conducted in 2019 and 2021, and the survey was applied to the residents of the metropolitan area of Santos, a seashore of Sao Paulo State. Four hundred and twenty-two participants (women = 254 and men = 168) were eligible. Baecke questionnaire for the elderly was applied for the classification as physically inactive (PI) or active (PA). Cognitive function was assessed by the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR). Participants were also stratified by schooling status for both sexes. RESULTS: Higher education had a sex-independent positive influence on MMSE and CDR (p < 0.001). PA influences positively MMSE in older women (PI: 25±5 and PA: 27±3, p < 0.03), but has no effect in older men (26±5 and 25±5, p > 0.05). Concordantly, older women who were PA (1.7 and 0 %) showed a lower prevalence of dementia compared with PI (6.2 and 2.1%), for mild and moderate respectively. Active older women had higher odds of improving the MMSE score (OR: 1.093; 95% CI: 1.008-1.186) than men (OR: 0.97 (95% CI: 0.896-1.051). CONCLUSION: Education affects cognitive function equally in Brazilian elderly whereas older women are more responsive to the beneficial effects of PA for dementia than men.

Effects of long-term social isolation on central, behavioural and metabolic parameters in middle-aged mice.

Social isolation gained discussion momentum due to the COVID-19 pandemic. Whereas many studies address the effects of long-term social isolation in post-weaning and adolescence and for periods ranging from 4 to 12 weeks, little is known about the repercussions of adult long-term social isolation in middle age. Thus, our aim was to investigate how long-term social isolation can influence metabolic, behavioural, and central nervous system-related areas in middle-aged mice. Adult male C57Bl/6 mice (4 months-old) were randomly divided into Social (2 cages, n = 5/cage) and Isolated (10 cages, n = 1/cage) housing groups, totalizing 30 weeks of social isolation, which ended concomitantly with the onset of middle age of mice. At the end of the trial, metabolic parameters, short-term memory, anxiety-like behaviour, and physical activity were assessed. Immunohistochemistry in the hippocampus (ΔFosB, BDNF, and 8OHDG) and hypothalamus (ΔFosB) was also performed. The Isolated group showed impaired memory along with a decrease in hippocampal ΔFosB at dentate gyrus and in BDNF at CA3. Food intake was also affected, but the direction depended on how it was measured in the Social group (individually or in the group) with no alteration in ΔFosB at the hypothalamus. Physical activity parameters increased with chronic isolation, but in the light cycle (inactive phase), with some evidence of anxiety-like behaviour. Future studies should better explore the timepoint at which the alterations found begin. In conclusion, long-term social isolation in adult mice contributes to alterations in feeding, physical activity pattern, and anxiety-like behaviour. Moreover, short-term memory deficit was associated with lower levels of hippocampal ΔFosB and BDNF in middle age.

The effect of replacing sedentary behavior by different intensities of physical activity in body composition: a systematic review / O efeito da substituição de comportamento sedentário por atividade física de diferentes intensidades na composição corporal: uma revisão sistemática

INTRODUCTION: The isotemporal substitution model (ISM) is a statistical approach that estimates the effects of replacing, in minutes, a block of physical activity or sedentary behavior by another block with different intensity. Previous studies have used the ISM to evaluate the effect of different isotemporal substitutions on body composition. Thus, the ISM can contribute to the understanding of changes in body composition related to distinct lifestyles and, hence, guiding future recommendations for maintaining and/or improving body composition. OBJECTIVE: To review the effect of replacing sedentary behavior by physical activity on body composition change analyzed through ISM. METHODS: Original articles in English were identified from searches in PubMed and Periódicos Capes databases. The search was carried out by two researchers. Last search was performed in October 2020. RESULTS: A total of 17 included articles, which evaluated different applications of ISM in relation to body composition change, mostly obtained by BMI and body fat. The physical activity was mainly assessed by using an accelerometer. Several methodological differences among the included studies limited comparisons between findings, including the sample profile and cut off points for physical activity. CONCLUSION: Among the studies that evaluate the effect of replacing sedentary behavior for different intensities of physical activity through ISM, replacing sedentary behavior by moderate-to-vigorous physical activity presented a more consistent effect in body composition change in comparison to replacement by other physical activity intensities, even for small blocks of time (five minutes).