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The prefrontal cortex (PFC) enables mammals to respond to situations, including internal states, with appropriate actions. One such internal state could be ‘tiredness’. Here, using activity tagging in the mouse PFC, we identified particularly excitable, fast-spiking, somatostatin-expressing, γ-aminobutyric acid (GABA) (PFCSst-GABA) cells that responded to sleep deprivation. These cells projected to the lateral preoptic (LPO) hypothalamus and the lateral hypothalamus (LH). Stimulating PFCSst-GABAterminals in the LPO hypothalamus caused sleep-preparatory behavior (nesting, elevated theta power and elevated temperature), and stimulating PFCSst-GABAterminals in the LH mimicked recovery sleep (non-rapid eye-movement sleep with higher delta power and lower body temperature). PFCSst-GABAterminals had enhanced activity during nesting and sleep, inducing inhibitory postsynaptic currents on diverse cells in the LPO hypothalamus and the LH. The PFC also might feature in deciding sleep location in the absence of excessive fatigue. These findings suggest that the PFC instructs the hypothalamus to ensure that optimal sleep takes place in a suitable place.

Polypharmacy in older adults is associated with multiple negative consequences that may affect muscular function, independently from the presence of medical conditions. The aim of this systematic review and meta‐analysis was to investigate the association of sarcopenia with polypharmacy and higher number of medications. A systematic literature search of observational studies using PubMed, Web of Science, Scopus and Cochrane Library databases was conducted from inception until June 2022. To determine if sarcopenia is associated with a higher risk of polypharmacy and increased number of medications, a meta‐analysis using a random‐effects model was used to calculate the pooled effects (CRD42022337539). Twenty‐nine studies were included in the systematic review and meta‐analysis. Sarcopenia was associated with a higher prevalence of polypharmacy (odds ratio [OR]: 1.65, 95% confidence interval [CI] [1.23, 2.20], I2= 84%, P< 0.01) and higher number of medications (mean difference: 1.39, 95% CI [0.59, 2.19], I2= 95%, P< 0.01) compared with individuals without sarcopenia. Using meta‐regression, a high variance was observed due to different populations (i.e., community‐dwelling, nursing home residents, inpatients, outpatients) for both outcomes of polypharmacy (r= −0.338, SE = 0.1669, 95% CI [−0.67, −0.01], z= −2.03, P= 0.04) and number of medications (r= 0.589, SE = 0.2615, 95% CI [0.08, 1.10], z= 2.25, P= 0.02). This systematic review and meta‐analysis reported a significantly increased risk of polypharmacy and higher number of medications in people with sarcopenia compared with individuals without this condition. Future research should clarify whether the specificity and number of medications is a direct contributor in accelerating the progression of muscle wasting and dysfunction contributing to sarcopenia in older adults.

Low handgrip strength, a hallmark measure of whole-body strength, has been linked with greater odds of cognitive decline and dementia; however, conflicting findings, which could be due to population characteristics and choice of tools, such for the assessment of handgrip strength and cognitive function domains, also exist. Therefore, we examined the relationship of handgrip strength with a comprehensive list of tests to assess domains of cognitive function using a representative sample of US older men and women without neurodegenerative disorders such as dementia. We analyzed cross-sectional data from the US National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014, with a study cohort of 777 older adults (380 men and 397 women) above 60 years of age. Handgrip strength was assessed using a handgrip dynamometer, while cognitive function was assessed through the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word List Learning Test (WLLT), Word List Recall Test (WLRT), Intrusion Word Count Test (WLLT-IC and WLRT-IC), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Sex-stratified multiple linear regression analyses were performed upon covariate adjustment for age, ethnicity, socio-economic status, education, medical history, body mass index, physical activity, energy, protein, and alcohol intake. Maximal handgrip strength was positively associated with cognitive function scores, including CERAD WLLT (P= 0.009, R2= 0.146) and AFT (P= 0.022, R2= 0.024) in older men, but not in women (CERAD WLLT: P= 0.253, AFT: P= 0.370). No significant associations with CERAD WLLRT (men: P= 0.057, women: P= 0.976), WLLT-IC (men: P= 0.671, women: P= 0.869), WLLRT-IC (men: P= 0.111, women: P= 0.861), and DSST (men: P= 0.108, women: P= 0.091) were observed. Dose–response curves exhibited a prominent linear relationship between all significant associations after covariate adjustment, with no indication of a plateau in these relationships. In conclusion, higher handgrip strength was independently associated with better learning ability for novel verbal information and verbal fluency in US men over the age of 60 and without dementia. Longitudinal studies are required to confirm whether muscle strength independently predicts cognitive function changes in older adults in a sex-specific manner, and whether this connection is affirmed to the possibility of reverse causation due to declines in physical activity levels in the preclinical phase of dementia.

Probiotics have shown potential to counteract sarcopenia, although the extent to which they can influence domains of sarcopenia such as muscle mass and strength in humans is unclear. The aim of this systematic review and meta‐analysis was to explore the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. A literature search of randomized controlled trials (RCTs) was conducted through PubMed, Scopus, Web of Science and Cochrane Library from inception until June 2022. Eligible RCTs compared the effect of probiotic supplementation versus placebo on muscle and total lean mass and global muscle strength (composite score of all muscle strength outcomes) in adults (>18 years). To evaluate the differences between groups, a meta‐analysis was conducted using the random effects inverse‐variance model by utilizing standardized mean differences. Twenty‐four studies were included in the systematic review and meta‐analysis exploring the effects of probiotics on muscle mass, total lean mass and global muscle strength. Our main analysis (k= 10) revealed that muscle mass was improved following probiotics compared with placebo (SMD: 0.42, 95% CI: 0.10–0.74, I2= 57%, P= 0.009), although no changes were revealed in relation to total lean mass (k= 12; SMD: ‐0.03, 95% CI: −0.19 – 0.13, I2= 0%, P= 0.69). Interestingly, a significant increase in global muscle strength was also observed among six RCTs (SMD: 0.69, 95% CI: 0.33–1.06, I2= 64%, P= 0.0002). Probiotic supplementation enhances both muscle mass and global muscle strength; however, no beneficial effects were observed in total lean mass. Investigating the physiological mechanisms underpinning different ageing groups and elucidating appropriate probiotic strains for optimal gains in muscle mass and strength are warranted.

Vitamin D supplementation is proposed as a potentially effective nutritional intervention to mitigate the risk of sarcopenia. The aim of this systematic review and meta‐analysis was to investigate the impact of vitamin D supplementation monotherapy on indices of sarcopenia in community‐dwelling older adults. A comprehensive search of the literature was conducted in PubMed, Web of Science, Scopus, and Cochrane Library. Eligible randomized controlled trials (RCTs) compared the effect of vitamin D supplementation (as monotherapy) with placebo on indices of sarcopenia in older (>50 years) adults. Using the random effects inverse‐variance model, we calculated the mean difference (MD) in handgrip strength (HGS), short physical performance battery (SPPB), timed up and go (TUG), and appendicular lean mass (ALM) between groups. We also calculated the standardized mean difference (SMD) in general muscle strength and general physical performance (composite plot of all muscle strength and physical performance outcomes, respectively) between groups. Ten RCTs were included in the meta‐analysis. A significant decrease in SPPB scores was observed with vitamin D supplementation compared with placebo (MD: −0.23; 95% CI −0.40 to −0.06; I2= 0%; P= 0.007). Vitamin D supplementation conferred no effect on HGS (MD: −0.07 kg; 95% CI −0.70 to 0.55; I2= 51%, P= 0.82), TUG (MD: 0.07 s; 95% CI −0.08 to 0.22; I2= 0%, P= 0.35), ALM (MD: 0.06 kg/m2; 95% CI: −0.32 to 0.44; I2= 73%, P= 0.77), general muscle strength (SMD: −0.01; 95% CI −0.17 to 0.15; I2= 42%, P= 0.90), or general physical performance (SMD: −0.02; 95% CI −0.23 to 0.18; I2= 71%, P= 0.83). Vitamin D supplementation did not improve any sarcopenia indices in community‐dwelling older adults and may compromise some aspects of physical performance. Future studies are warranted to investigate the impact of vitamin D supplementation on individual indices of SPPB, including mobility and balance, in older adults.