Age-related Decline Research Articles

Milk Fat Globule Membranes for Mental Health across the Human Lifespan.

The milk fat globule membrane (MFGM) contains bioactive proteins, carbohydrates, and lipids. Polar lipids found in the MFGM play a critical role in maintaining cell membrane integrity and neuronal signalling capacity, thereby supporting brain health. This review summarises the literature on the MFGM and its phospholipid constituents for improvement of mental health across three key stages of the human lifespan, i.e., infancy, adulthood, and older age. MFGM supplementation may improve mental health by reducing neuroinflammation and supporting neurotransmitter synthesis through the gut-brain axis. Fortification of infant formula with MFGMs is designed to mimic the composition of breastmilk and optimise early gut and central nervous system development. Early behavioural and emotional development sets the stage for future mental health. In adults, promising results suggest that MFGMs can reduce the negative consequences of situational stress. Preclinical models of age-related cognitive decline suggest a role for the MFGM in supporting brain health in older age and reducing depressive symptoms. While there is preclinical and clinical evidence to support the use of MFGM supplementation for improved mental health, human studies with mental health as the primary target outcome are sparce. Further high-quality clinical trials examining the potential of the MFGM for psychological health improvement are important.

Proteomic reference map for sarcopenia research: mass spectrometric identification of key muscle proteins of organelles, cellular signaling, bioenergetic metabolism and molecular chaperoning.

During the natural aging process, frailty is often associated with abnormal muscular performance. Although inter-individual differences exit, in most elderly the tissue mass and physiological functionality of voluntary muscles drastically decreases. In order to study age-related contractile decline, animal model research is of central importance in the field of biogerontology. Here we have analyzed wild type mouse muscle to establish a proteomic map of crude tissue extracts. Proteomics is an advanced and large-scale biochemical method that attempts to identify all accessible proteins in a given biological sample. It is a technology-driven approach that uses mass spectrometry for the characterization of individual protein species. Total protein extracts were used in this study in order to minimize the potential introduction of artefacts due to excess subcellular fractionation procedures. In this report, the proteomic survey of aged muscles has focused on organellar marker proteins, as well as proteins that are involved in cellular signaling, the regulation of ion homeostasis, bioenergetic metabolism and molecular chaperoning. Hence, this study has establish a proteomic reference map of a highly suitable model system for future aging research.

Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes.

Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age. Our findings primarily revealed distinct proteomic profiles between immature fully grown germinal vesicle and mature metaphase II oocytes. Importantly, we further show that a woman's age is associated with changes in her oocyte proteome. Specifically, when compared to oocytes obtained from young women, advanced maternal age oocytes exhibited lower levels of the proteasome and TRiC complex, as well as other key regulators of proteostasis and meiosis. This suggests that aging adversely affects the proteostasis and meiosis networks in human oocytes. The proteins identified in this study hold potential as targets for improving oocyte quality and may guide future studies into the molecular processes underlying oocyte aging.

Hidden Dangers of Frailty: Higher Mortality, Complications and Costs in Acute Pancreatitis.

Frailty is a clinically recognizable state of increased vulnerability due to age-related decline in reserve and function across multiple physiologic systems that compromises the ability to cope with acute stress. As frailty is being identified as an important risk factor in outcomes of gastrointestinal pathologies, we aimed to assess outcomes in patients with acute pancreatitis within this cohort. We conducted a retrospective study using the Nationwide Inpatient Sample (NIS) database. ICD-10 codes were used to inquire for patients admitted with acute pancreatitis between September 2015 through 2017. ICD-10 codes corresponding to the Hospital Frailty Risk Score (HFRS) were used to divide the study sample into 2 cohorts: low risk (< 5 points) and intermediate or high risk (> 5 points). To calculate the points, we fitted a logistic regression model that included membership of the frail group as the binary dependent variable (frail vs. non-frail) and the set of ICD-10 codes as binary predictor variables (1 = present, 0 = absent for each code). To simplify the calculation and interpretation, we multiplied regression coefficients by five to create a points system, so that a certain number of points are awarded for each ICD-10 code and added together to create the final frailty risk score. Multivariate regression analysis was performed to find adjusted mortality. Out of a total of 1,267,744 patients admitted with acute pancreatitis, 728,953 (57.5%) were identified as intermediate and high risk (> 5 points) (study cohort) and 538,781 (42.5%) as low risk (< 5 points). The mean age in the study cohort was 64.8 ± 12.6 and that in the low-risk group was 58.6 ± 9.5. Most of the patients in both groups were males and Caucasians; Medicare was the predominant insurance provider. A majority of the admissions in both groups were in an urban teaching hospital and were emergency. (Table1). The primary outcome was in-hospital mortality which was significantly higher in the study cohort as compared to the low-risk group (4.3% vs. 2.5%, p < 0.0001). The age-adjusted Odds ratio of mortality was 1.72(95% CI (Confidence Interval) 1.65-1.80, p < 0.05). When compared between the two groups; median length of stay (6 vs. 4); hospitalization cost ($14,412 vs. $10,193), disposition to a skilled nursing facility (SNF) (17.1% vs. 8.6%) and need for home health care (HHC) was significantly higher in the study cohort. Complications like septicemia, septic shock, and acute kidney injury were also higher in the study group (Table2). Table1 Baseline demographics of the cohort Characteristics Acute pancreatitis with High HES Frailty score (> 5, intermediate + high) Acute pancreatitis with low HES Frailty score (< 5) P-value N = 1,267,744 N = 728,953 (57.5%) N = 538,781 (42.5%) Age Mean years (Mean ± SD) 64.8 ± 12.6 58.6 ± 9.5 < 0.001 Gender < 0.001 Male 59.1% 52.3% Female 40.9% 47.7% *Missing-475 Age groups < 0.001 18-44 3.7% 14.3% 45-64 48% 52.9% 65-84 32.2% 28.7% ≥ 85 16.1% 4.1% Race < 0.001 Caucasians 67.4% 61.9% African Americans 9.6% 16.8% Others 23% 21.3% *Missing-10 Insurance type < 0.001 Medicare 40.9% 36.3% Medicaid 17.2% 24.3% Private 31.8% 27.9% Other 9.9% 11.4% *Missing-75 Active smoking 32.7% 37.9% 0.005 Biliary Stone 36.2% 16.7% < 0.001 Admission Type < 0.001 Emergent 93.7% 94.3% Elective 6.3% 5.7% *Missing-2880 Hospital ownership/control < 0.001 Rural 7.8% 10% Urban nonteaching 26.3% 26.6% Urban teaching 65.9% 63.4% Table2 Outcomes Outcomes Acute pancreatitis with High HES Frailty score (> 5, intermediate + high) Acute pancreatitis with low HES Frailty score (< 5) P-value In-hospital mortality *Missing-920 4.3% 2.5% < .0001 1.72(1.65-1.80) < .0001 Length of stay, days (Median,IQR) 6(3-8) 4(2-6) < .0001 Total hospitalization cost, $ (Median,IQR) 14,412(8843-20,216) 10,193(6840-13,842) < .0001 In-Hospital Complications ARDS 0.4% 0.3% 0.08 Ventilator dependence respiratory failure 0.23% 0.29% 0.25 Septicemia 15.2% 9.6% < .0001 Septic Shock 6.1% 2.9% < .0001 AKI 24.8% 14.9% < .0001 Disposition < .0001 Discharge to home 58.9% 74.9% Transfer other: includes Skilled Nursing Facility (SNF), Intermediate Care Facility (ICF), and another type of facility 17.1% 8.6% Home health care 11.5% 8.1% Against medical advice (AMA) 1.6% 3.4% *Missing-920 CONCLUSION: Using frailty as a construct to identify those who are at greater risk for adverse outcomes, can help formulate interventions to target individualized reversible factors to improve outcomes in patients with acute pancreatitis. Future large-scale prospective studies are warranted to understand the dynamic and longitudinal relationship between pancreatitis and frailty.

Can Brief Listening to Mozart's Music Improve Visual Working Memory? An Update on the Role of Cognitive and Emotional Factors.

The aim of this research was to enhance understanding of the relationship between brief music listening and working memory (WM) functions. The study extends a previous large-scale experiment in which the effects of brief exposure to music on verbal WM were explored. In the present second phase of the experiment, these effects were assessed for the visuospatial subcomponent of WM. For that aim, visuospatial WM was measured using the Corsi blocks task-backwards and Visual Patterns Test in a large sample of 311 young and older adults after being exposed to musical excerpts coming from different music composers (Mozart, Vivaldi, Glass). To account for possible effects of arousal, a silence condition was used. Individual preference for music excerpts and emotional reactions to each condition were also subjectively rated using the Positive and Negative Affect Schedule (PANAS) to account for the role of emotional reactions in shaping subsequent cognitive performance. Results showed that music affected the visuospatial sketchpad of WM. In line with the previously described Mozart effect, only Mozart's music had a significant positive impact on visuospatial WM in the two age groups, regardless of preferences, and on overall age-related WM decline in older adults. The Mozart effect was more prominent for the VPT than the Corsi task and was also expressed for the prevailing positive effect. These observations are in contrast to the selective influence of Vivaldi's music on verbal WM that was detected in our first study. Together, the results demonstrate a differential music influence on the phonological loop and on the visuospatial sketchpad. They thus contribute to the debate of whether music has the potential to affect distinct processes within working memory in an excerpt- or composer-specific manner. Also, they suggest that emotional activation and central executive attention are essentially involved in modulating the influence of music on subsequent cognition. These findings can assist in the selection of music excerpts used in cognitive rehabilitation programs that focus on visuospatial skills.

The effects of omega-3 polyunsaturated fatty acids on muscle and whole-body protein synthesis: a systematic review and meta-analysis.

Sarcopenia describes the age-related decline in skeletal muscle mass and strength that is driven, at least in part, by an imbalance between rates of muscle protein synthesis (MPS) and muscle protein breakdown. An expanding body of literature has examined the effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) ingestion on MPS rates in older adults, with mixed findings. The aim of this systematic review and meta-analysis was to investigate the effectiveness of n-3 PUFA ingestion in stimulating rates of MPS and whole-body protein synthesis in healthy adults and clinical populations. Searches were conducted of the PubMed, Web of Science, Cochrane Library, and Scopus databases from inception until December 2022 for articles on randomized controlled trials comparing the effect of n-3 PUFA ingestion vs a control or placebo on rates of MPS and whole-body protein synthesis. The search yielded 302 studies, of which 8 were eligible for inclusion. The random effects inverse-variance model was used and standardized mean differences (SMDs) with 95%CIs were calculated to assess the pooled effect. Risk of bias was assessed by the Cochrane Risk-of-Bias 2 tool. The main analysis indicated no effect of n-3 PUFA supplementation on MPS rates (k = 6; SMD: 0.03; 95%CI, -0.35 to 0.40; I2 = 30%; P = .89). Subgroup analysis based on age, n-3 PUFA dose, duration of supplementation, and method used to measure fractional synthetic rate also revealed no effect of n-3 PUFA ingestion on MPS. In contrast, the main analysis demonstrated an effect of n-3 PUFA ingestion on increasing whole-body protein synthesis rates (k = 3; SMD: 0.51; 95%CI, 0.12-0.90; I2 = 0%; P = .01). n-3 PUFA ingestion augments the stimulation of whole-body protein synthesis rates in healthy adults and clinical populations. PROSPERO registration no. 42022366986.

A Potential Measure of Premorbid Functioning: Evaluating the Construct Validity of the Author and Magazine Recognition Tests.

To establish convergent and discriminant validity for a combined measure of print exposure (i.e., Author Recognition Test and Magazine Recognition Test [ART/MRT]) and assess its potential utility for estimating premorbid cognitive functioning. Community-dwelling older adults (N = 84; 95% non-Hispanic White) completed the ART/MRT, Test of Premorbid Functioning (ToPF), Dementia Rating Scale - 2nd Edition (DRS-2), Hopkins Verbal Learning Test - Revised (HVLT-R-DR), and select subtests from the Delis-Kaplan Executive Functioning System (D-KEFS) as measures of executive functioning (i.e., D-KEFS-EF) and processing speed (i.e., D-KEFS-PS). Pearson correlations and linear regressions were used to examine the relationships between the ART/MRT, cognition, and demographics. Cognitive scores, with the exception of HVLT-R-DR, were positively correlated with ART/MRT score such that better cognitive performance was associated with greater print exposure (range r = 0.39-0.49). ART/MRT score was positively correlated with years of education and negatively correlated with age. ToPF and DRS-2 differentially and uniquely predicted ART/MRT score beyond the other cognitive and demographic variables and beyond each other. Findings indicate that measures of print exposure reflect crystallized knowledge but may also capture fluid abilities that may be more vulnerable to age-related decline or neurodegeneration. Assessment of print exposure may offer an alternative to word reading measures that may be inappropriate for translation into other languages and for use with individuals with certain language difficulties.

Intravascular Laser Blood Irradiation (ILIB) Enhances Antioxidant Activity and Energy Metabolism in Aging Ovaries.

Ovarian aging is characterized by the accumulation of free radicals, leading to tissue damage and affecting reproductive health. Intravascular laser irradiation of blood (ILIB, using a low-energy He-Ne laser) is known for its efficacy in treating vascular-related diseases by reducing free radicals and inflammation. However, its impact on ovarian aging remains unexplored. This study aimed to investigate the effects of ILIB on oxidative stress and energy metabolism in aging ovaries. Genetic analysis was conducted on 75 infertile patients with aging ovaries, divided into ILIB-treated and control (CTRL) groups. Patients underwent two courses of laser treatment, and clinical parameters were evaluated. Cumulus cells were collected for the genetic analysis of oxeiptosis, glycolysis, and the tricarboxylic acid (TCA) cycle. The analysis of gene expression patterns revealed intriguing findings in ILIB-treated patients compared to the untreated group. Notably, ILIB treatment resulted in significant upregulation of oxeiptosis-related genes AIFM1 and NRF2, suggesting a potential protective effect against oxidative stress-induced cell death. Furthermore, ILIB treatment led to a downregulation of glycolysis-associated gene hexokinase 2 (HK2), indicating a shift away from anaerobic metabolism, along with an increase in PDHA levels, indicative of enhanced mitochondrial function. Consistent with these changes, ILIB-treated patients exhibited elevated expression of the key TCA cycle genes citrate synthase (CS), succinate dehydrogenase complex subunit A (SDHA), and fumarate hydratase (FH), signifying improved energy metabolism. The findings from this study underscore the potential of ILIB as a therapeutic strategy for mitigating ovarian aging. By targeting oxidative stress and enhancing energy metabolism, ILIB holds promise for preserving ovarian function and reproductive health in aging individuals. Further research is warranted to elucidate the underlying mechanisms and optimize the application of ILIB in clinical settings, with the ultimate goal of improving fertility outcomes in women experiencing age-related ovarian decline.

SVHRSP Alleviates Age-Related Cognitive Deficiency by Reducing Oxidative Stress and Neuroinflammation.

Our previous studies have shown that scorpion venom heat-resistant synthesized peptide (SVHRSP) induces a significant extension in lifespan and improvements in age-related physiological functions in worms. However, the mechanism underlying the potential anti-aging effects of SVHRSP in mammals remains elusive. Following SVHRSP treatment in senescence-accelerated mouse resistant 1 (SAMR1) or senescence-accelerated mouse prone 8 (SAMP8) mice, behavioral tests were conducted and brain tissues were collected for morphological analysis, electrophysiology experiments, flow cytometry, and protein or gene expression. The human neuroblastoma cell line (SH-SY5Y) was subjected to H2O2 treatment in cell experiments, aiming to establish a cytotoxic model that mimics cellular senescence. This model was utilized to investigate the regulatory mechanisms underlying oxidative stress and neuroinflammation associated with age-related cognitive impairment mediated by SVHRSP. SVHRSP significantly ameliorated age-related cognitive decline, enhanced long-term potentiation, restored synaptic loss, and upregulated the expression of synaptic proteins, therefore indicating an improvement in synaptic plasticity. Moreover, SVHRSP demonstrated a decline in senescent markers, including SA-β-gal enzyme activity, P16, P21, SIRT1, and cell cycle arrest. The underlying mechanisms involve an upregulation of antioxidant enzyme activity and a reduction in oxidative stress-induced damage. Furthermore, SVHRSP regulated the nucleoplasmic distribution of NRF2 through the SIRT1-P53 pathway. Further investigation indicated a reduction in the expression of proinflammatory factors in the brain after SVHRSP treatment. SVHRSP attenuated neuroinflammation by regulating the NF-κB nucleoplasmic distribution and inhibiting microglial and astrocytic activation through the SIRT1-NF-κB pathway. Additionally, SVHRSP significantly augmented Nissl body count while suppressing neuronal loss. SVHRSP could remarkably improve cognitive deficiency by inhibiting oxidative stress and neuroinflammation, thus representing an effective strategy to improve brain health.

Exploring animal protein sources against prevent age-related short-term memory decline in mice: Dietary fish (Alaska Pollock) protein exhibits superior protective effects.

Dietary factors, particularly proteins, have been extensively explored to combat cognitive impairment. We have previously reported that dietary fish (Alaska Pollock) protein (APP) is more effective than casein (CAS) or fish oil in maintaining short-term memory in senescence-accelerated mice prone 10 (SAMP10). To examine the specificity of the protective effect of APP intakes against short-term memory decline, we assessed the impact of various dietary animal proteins, including APP, CAS, chicken breast protein (CP), and whey protein (WP), against age-related cognitive function in SAMP10 mice. After feeding the experimental diets for 5 months, memory was assessed using the Y-maze. The APP group exhibited a significant increase in spontaneous alternation behavior as an indicator of working memory when group compared with groups fed with other protein source. Additionally, the APP group displayed significantly higher neurofilament heavy chain positivity than the CAS and CP groups, as evidenced immunohistochemical analysis. Gut microbiota analysis indicated that dietary APP significantly enhanced the relative abundance of Lactobacillus, which positively correlated with spontaneous alternation behavior. Collectively, these findings suggest that dietary APP is more effective than CAS, CP, or WP in preventing age-related short-term memory decline and morphological abnormalities in the hippocampal axons of SAMP10 mice. Moreover, APP-mediated improvements in cognitive deficits may be associated with changes in microbiota diversity. PRACTICAL APPLICATION: This research suggests that dietary fish protein from Alaska Pollock may be more efficient in prevention short-term memory decline in mice, compared to other animal proteins. This finding has practical implications for nutritional optimization, developing the new health food products, and elucidating the relationship between the impact of specific proteins on gut microbiota and prevention of age-related cognitive decline.

Validation of Hospital Frailty Risk Score in Heart Failure

Background: Frailty is prevalent in older people and results from age-related decline in physiological function and reserve. The objective of this study was to validate the Hospital Frailty Risk Score (HFRS) in predicting outcomes and hospitalisation usage in older hospitalised heart failure (HF) patients. Methods: This study was a retrospective review of electronic medical records. Patients aged ≥65 years admitted with HF to a Singapore tertiary hospital between 1 January 2021 and 30 April 2021 were included. Patients were identified as HF patients in the value-driven care pathway and using ICD codes for HF. They were categorised into low risk (&lt;5), intermediate risk (5–15) and high risk (&gt;15) of frailty using the HFRS. Results: A total of 208 older patients with HF were included (mean age 79.4 years; 50.5% males). Using the HFRS, 35.1% were deemed at low risk, 46.2% at intermediate risk and 18.8% at high risk of frailty. Those at high risk of frailty were older than those at low risk (mean age 84.8 versus 76.5 years, respectively; p&lt;0.001). Women had a higher risk of frailty than men. Univariate analyses showed longer length of stay (LOS) and higher 30-, 90- and 365-day mortality in those at high frailty risk. In multivariate analyses, HFRS was associated with long LOS, 90-day and 1-year mortality. Dementia, acute MI and renal disease were more common in high-risk patients. Comparing HFRS with the Charlson Comorbidity Index (CCI), HFRS was a better predictor of long LOS, mortality at 30, 90, 1 year and 30-day readmission than CCI. HFRS alone was a better predictor than combining the HFRS and CCI. Conclusion: Older patients with higher HFRS have increased healthcare utilisation, including longer LOS and higher mortality.

MDM2 accelerated renal senescence via ubiquitination and degradation of HDAC1.

Senescence, an intricate and inevitable biological process, characterized by the gradual loss of homeostasis and declining organ functions. The pathological features of cellular senescence, including cell cycle arrest, metabolic disruptions, and the emergence of senescence-associated secretory phenotypes (SASP), collectively contribute to the intricate and multifaceted nature of senescence. Beyond its classical interaction with p53, murine double minute gene 2 (MDM2), traditionally known as an E3 ubiquitin ligase involved in protein degradation, plays a pivotal role in cellular processes governing senescence. Histone deacetylase (HDAC), a class of histone deacetylases mainly expressed in the nucleus, has emerged as a critical contributor to renal tissues senescence. In this study we investigated the interplay between MDM2 and HDAC1 in renal senescence. We established a natural aging model in mice over a 2-year period that was verified by SA-β-GAL staining and increased expression of senescence-associated markers such as p21, p16, and TNF-α in the kidneys. Furthermore, we showed that the expression of MDM2 was markedly increased, while HDAC1 expression underwent downregulation during renal senescence. This phenomenon was confirmed in H2O2-stimulated HK2 cells in vitro. Knockout of renal tubular MDM2 alleviated renal senescence in aged mice and in H2O2-stimulated HK2 cells. Moreover, we demonstrated that MDM2 promoted renal senescence by orchestrating the ubiquitination and subsequent degradation of HDAC1. These mechanisms synergistically accelerate the aging process in renal tissues, highlighting the intricate interplay between MDM2 and HDAC1, underpinning the age-related organ function decline.

A cocktail of rapamycin, acarbose, and phenylbutyrate prevents age-related cognitive decline in mice by targeting multiple aging pathways

Aging is a primary risk factor for cognitive impairment and exacerbates multiple biological processes in the brain, including but not limited to nutrient sensing, insulin signaling, and histone deacetylation activity. Therefore, a pharmaceutical intervention of aging that targets distinct but overlapping pathways provides a basis for testing combinations of drugs as a cocktail. Our previous study showed that middle-aged mice treated with a cocktail of rapamycin, acarbose, and phenylbutyrate for 3 months had increased resilience to age-related cognitive decline. This finding provided the rationale to investigate the transcriptomic and molecular changes within the brains of mice that received this cocktail treatment or control treatment. Transcriptomic profiles were generated through ribonucleic acid (RNA) sequencing, and pathway analysis was performed by gene set enrichment analysis to evaluate the overall RNA message effect of the drug cocktail. Molecular endpoints representing aging pathways were measured using immunohistochemistry to further validate the attenuation of brain aging in the hippocampus of mice that received the cocktail treatment, each individual drug or control. Results showed that biological processes that enhance aging were suppressed, with an increased trend of autophagy in the brains of mice given the drug cocktail. The molecular endpoint assessments indicated that treatment with the drug cocktail was overall more effective than any of the individual drugs for relieving cognitive impairment by targeting multiple aging pathways.

Age-related differences in saccadic indices of top-down guidance via short-term memory during visual search.

Aging has been associated with significant declines in the speed and accuracy of visual search. These effects have been attributed partly to low-level (bottom-up) factors including reductions in sensory acuity and general processing speed. Aging is also associated with changes in top-down attentional control, but the impact of these on search is less well-understood. The present study investigated age-related differences in top-down attentional control by comparing the speed and accuracy of saccadic sampling in the presence and absence of top-down information about target color in young (YA) and older (OA) observers. Displays contained an equal number of red and blue Landholt stimuli. Targets were distinguished from distractors by a unique orientation, and observers reported the direction of the target's gap on each trial. Single-target cues signaled the color of the target with 100% validity. Dual-target cues indicated the target could be present in either colored subgroup. The results revealed reliable group differences in the benefits associated with top-down information on single-target cues compared to dual-target cues. On single-target searches, OA made significantly more saccades than YA to stimuli in the uncued color subset. Single-target cues also produced a smaller advantage in the time taken to fixate the target in OA compared to YA. These results support an age-related decline in observers' use of top-down information to restrict sequences of saccades to a task-relevant subset of objects during visual search. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Salvianolic acid B protects against UVB-induced skin aging via activation of NRF2

BackgroundProlonged exposure to sun radiation may result in harmful skin photoaging. Therefore, discovering novel anti-photoaging treatment modalities is critical. An active component isolated from Salvia miltiorrhiza (SM), Salvianolic acid B (Sal-B), is a robust antioxidant and anti-inflammatory agent. This investigation aimed to discover the therapeutic impact and pathways of salvianolic acid B for UVB-induced skin photoaging, an area that remains unexplored. MethodsWe conducted in vitro experiments on human dermal fibroblasts (HDFs) exposed to UVB radiation, assessing cellular senescence, superoxide dismutase (SOD) activity, cell viability, proliferation, migration, levels of reactive oxygen species (ROS), and mitochondrial health. The potential mechanism of Sal-B was analyzed using RNA sequencing, with further validation through Western blotting, PCR, and nuclear factor erythroid 2-related factor 2 (NRF2) silencing methods. In vivo, a model of skin photoaging induced by UVB in nude mice was employed. The collagen fiber levels were assessed utilizing hematoxylin and eosin (H&E), Masson, and Sirus red staining. Additionally, NRF2 and related gene and protein expression levels were identified utilizing PCR and Western blotting. ResultsSal-B was found to significantly counteract photoaging in UVB-exposed skin fibroblasts, reducing aging-related decline in fibroblast proliferation and an increase in apoptosis. It was observed that Sal-B aids in protecting mitochondria from excessive ROS production by promoting NRF2 nuclear translocation. NRF2 knockdown experiments established its necessity for Sal-B's anti-photoaging effects. The in vivo studies also verified Sal-B's anti-photoaging efficacy, surpassing that of tretinoin (Retino-A). These outcomes offer novel insights into the contribution of Sal-B in developing clinical treatment modalities for UVB-induced photodamage in skin fibroblasts. ConclusionIn this investigation, we identified the Sal-B protective impact on the senescence of dermal fibroblasts and skin photoaging induced by radiation of UVB. The outcomes suggest Sal-B as a potential modulator of the NRF2 signaling pathway.

Age- and sex-related changes in motor functions: a comprehensive assessment and component analysis.

Age-related motor impairments often cause caregiver dependency or even hospitalization. However, comprehensive investigations of the different motor abilities and the changes thereof across the adult lifespan remain sparse. We, therefore, extensively assessed essential basic and complex motor functions in 444 healthy adults covering a wide age range (range 21 to 88 years). Basic motor functions, here defined as simple isolated single or repetitive movements in one direction, were assessed by means of maximum grip strength (GS) and maximum finger-tapping frequency (FTF). Complex motor functions, comprising composite sequential movements involving both proximal and distal joints/muscle groups, were evaluated with the Action Research Arm Test (ARAT), the Jebsen-Taylor Hand Function Test (JTT), and the Purdue Pegboard Test. Men achieved higher scores than women concerning GS and FTF, whereas women stacked more pins per time than men during the Purdue Pegboard Test. There was no significant sex effect regarding JTT. We observed a significant but task-specific reduction of basic and complex motor performance scores across the adult lifespan. Linear regression analyses significantly predicted the participants' ages based on motor performance scores (R2 = 0.502). Of note, the ratio between the left- and right-hand performance remained stable across ages for all tests. Principal Component Analysis (PCA) revealed three motor components across all tests that represented dexterity, force, and speed. These components were consistently present in young (21-40 years), middle-aged (41-60 years), and older (61-88 years) adults, as well as in women and men. Based on the three motor components, K-means clustering analysis differentiated high- and low-performing participants across the adult life span. The rich motor data set of 444 healthy participants revealed age- and sex-dependent changes in essential basic and complex motor functions. Notably, the comprehensive assessment allowed for generating robust motor components across the adult lifespan. Our data may serve as a reference for future studies of healthy subjects and patients with motor deficits. Moreover, these findings emphasize the importance of comprehensively assessing different motor functions, including dexterity, force, and speed, to characterize human motor abilities and their age-related decline.

Failure of senolytic treatment to prevent cognitive decline in a female rodent model of aging.

There are sex differences in vulnerability and resilience to the stressors of aging and subsequent age-related cognitive decline. Cellular senescence occurs as a response to damaging or stress-inducing stimuli. The response includes a state of irreversible growth arrest, the development of a senescence-associated secretory phenotype, and the release of pro-inflammatory cytokines associated with aging and age-related diseases. Senolytics are compounds designed to eliminate senescent cells. Our recent work indicates that senolytic treatment preserves cognitive function in aging male F344 rats. The current study examined the effect of senolytic treatment on cognitive function in aging female rats. Female F344 rats (12 months) were treated with dasatinib (1.2 mg/kg) + quercetin (12 mg/kg) or ABT-263 (12 mg/kg) or vehicle for 7 months. Examination of the estrus cycle indicated that females had undergone estropause during treatment. Senolytic treatment may have increased sex differences in behavioral stress responsivity, particularly for the initial training on the cued version of the watermaze. However, pre-training on the cue task reduced stress responsivity for subsequent spatial training and all groups learned the spatial discrimination. In contrast to preserved memory observed in senolytic-treated males, all older females exhibited impaired episodic memory relative to young (6-month) females. We suggest that the senolytic treatment may not have been able to compensate for the loss of estradiol, which can act on aging mechanisms for anxiety and memory independent of cellular senescence.

Ageing, Cognitive Decline, and Effects of Physical Exercise: Complexities, and Considerations from Animal Models.

In our ageing global population, the cognitive decline associated with dementia and neurodegenerative diseases represents a major healthcare problem. To date, there are no effective treatments for age-related cognitive impairment, thus preventative strategies are urgently required. Physical exercise is gaining traction as a non-pharmacological approach to promote brain health. Adult hippocampal neurogenesis (AHN), a unique form of brain plasticity which is necessary for certain cognitive functions declines with age and is enhanced in response to exercise. Accumulating evidence from research in rodents suggests that physical exercise has beneficial effects on cognition through its proneurogenic capabilities. Given ethical and technical limitations in human studies, preclinical research in rodents is crucial for a better understanding of such exercise-induced brain and behavioural changes. In this review, exercise paradigms used in preclinical research are compared. We provide an overview of the effects of different exercise paradigms on age-related cognitive decline from middle-age until older-age. We discuss the relationship between the age-related decrease in AHN and the potential impact of exercise on mitigating this decline. We highlight the emerging literature on the impact of exercise on gut microbiota during ageing and consider the role of the gut-brain axis as a future possible strategy to optimize exercise-enhanced cognitive function. Finally, we propose a guideline for designing optimal exercise protocols in rodent studies, which would inform clinical research and contribute to developing preventative strategies for age-related cognitive decline.

Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition cohort participants

A leading explanation for translational failure in neurodegenerative disease is that new drugs are evaluated late in the disease course when clinical features have become irreversible. Here, to address this gap, we cognitively profiled 21,051 people aged 17–85 years as part of the Genes and Cognition cohort within the National Institute for Health and Care Research BioResource across England. We describe the cohort, present cognitive trajectories and show the potential utility. Surprisingly, when studied at scale, the APOE genotype had negligible impact on cognitive performance. Different cognitive domains had distinct genetic architectures, with one indicating brain region-specific activation of microglia and another with glycogen metabolism. Thus, the molecular and cellular mechanisms underpinning cognition are distinct from dementia risk loci, presenting different targets to slow down age-related cognitive decline. Participants can now be recalled stratified by genotype and cognitive phenotype for natural history and interventional studies of neurodegenerative and other disorders.

Investigating young children’s physical activity through time and place

BackgroundPrevious research indicates the start of primary school (4-5-year-old) as an essential period for the development of children’s physical activity (PA) patterns, as from this point, the age-related decline of PA is most often observed. During this period, young children are exposed to a wider variety of environmental- and social contexts and therefore their PA is influenced by more diverse factors. However, in order to understand children’s daily PA patterns and identify relevant opportunities for PA promotion, it is important to further unravel in which (social) contexts throughout the day, PA of young children takes place.MethodsWe included a cross-national sample of 21 primary schools from the Startvaardig study. In total, 248 children provided valid accelerometer and global positioning (GPS) data. Geospatial analyses were conducted to quantify PA in (social) environments based on their school and home. Transport-related PA was evaluated using GPS speed-algorithms. PA was analysed at different environments, time-periods and for week- and weekend days separately.ResultsChildren accumulated an average of 60 min of moderate-to-vigorous PA (MVPA), both during week- and weekend days. Schools contributed to approximately half of daily MVPA during weekdays. During weekends, environments within 100 m from home were important, as well as locations outside the home-school neighbourhood. Pedestrian trips contributed to almost half of the daily MVPA.ConclusionsWe identified several social contexts relevant for children’s daily MVPA. Schools have the potential to significantly contribute to young children’s PA patterns and are therefore encouraged to systematically evaluate and implement parts of the school-system that stimulate PA and potentially also learning processes. Pedestrian trips also have substantial contribution to daily MVPA of young children, which highlights the importance of daily active transport in school- and parental routines.