Age-related Decline Research Articles

Polyploidy-mediated resilience in hepatic aging: molecular mechanisms and functional implication

Abstract Background Polyploidization, a process where cells acquire additional chromosome sets, is a unique characteristic of hepatocytes. This process has been increasingly recognized as an adaptive mechanism for maintaining liver function during aging, a period characterized by cellular senescence, DNA damage, and metabolic dysregulation. Purpose This review explores the molecular mechanisms underlying hepatocyte polyploidization and its potential role in promoting resilience against the aging-related decline in liver function. We assess how polyploid hepatocytes contribute to genomic stability, stress resistance, and metabolic adaptation, highlighting their relevance to liver aging. Main body Hepatocyte polyploidization occurs through mechanisms such as cytokinesis failure and endoreplication, leading to binuclear or mononuclear polyploid cells. Polyploid hepatocytes exhibit enhanced DNA repair capacity, which helps mitigate the accumulation of age-related genomic damage. The increased gene dosage in polyploid cells facilitates better stress responses, particularly against oxidative stress and genotoxic insults. Metabolic adaptations, including enhanced xenobiotic metabolism and lipid regulation, further support the liver’s ability to maintain homeostasis during aging. Additionally, polyploid cells demonstrate altered epigenetic landscapes and proteostasis mechanisms, contributing to improved cellular function and reduced susceptibility to senescence. These adaptations collectively enhance liver resilience against age-related metabolic and structural challenges. Conclusion Hepatocyte polyploidization represents a critical protective mechanism in liver aging, promoting cellular adaptations that safeguard against genomic instability, metabolic dysfunction, and oxidative stress. Understanding the molecular pathways driving polyploidization could pave the way for novel therapeutic strategies to combat age-related liver disorders and enhance health span. Graphical Abstract

The Impact of Ageing on Episodic Memory Retrieval: How Valence Influences Neural Functional Connectivity

Age-related decline in episodic memory is often linked to structural and functional changes in the brain. Here, we investigated how these alterations might affect functional connectivity during memory retrieval following exposure to emotional stimuli. Using functional magnetic resonance imaging (fMRI), participants viewed images with varying emotional valences (positive, negative, and neutral) followed by unrelated non-arousing videos and were then asked to retrieve an episodic detail from the previously shown video. We conducted Multivariate Pattern Analysis (MVPA) to identify regions with divergent responses between age groups, which then served as seeds in Seed-Based Connectivity (SBC) analyses. The results revealed an age-related decline in behavioural performance following exposure to negative stimuli but preserved performance following positive stimuli. Young adults exhibited increased functional connectivity following negative valence. Conversely, old adults displayed increased connectivity more scarcely, and only following positive valence. These findings point to an adaptive response of the impact of emotions on task performance that depends on neural adaptations related to ageing. This suggests that age-related changes in functional connectivity might underlie how emotions influence memory, highlighting the need to tailor memory support strategies in older adulthood.

Reactive oxygen species in age-related musculoskeletal decline: implications for nutritional intervention.

Musculoskeletal disorders and age-related musculoskeletal decline are major contributors to the burden of ill health seen in older subjects. Despite this increased burden, these chronic disorders of old age receive a relatively small proportion of national research funds. Much has been learned about fundamental processes involved in ageing from basic science research and this is leading to identification of key pathways that mediate ageing which may help the search for interventions to reduce age-related musculoskeletal decline. This short review will focus on the role of reactive oxygen species in age-related skeletal muscle decline and on the implications of this work for potential nutritional interventions in sarcopenia. The key physiological role of reactive oxygen species is now known to be in mediating redox signalling in muscle and other tissues and ageing leads to disruption of such pathways. In muscle, this is reflected in an age-related attenuation of specific adaptations and responses to contractile activity that impacts the ability of skeletal muscle from ageing individuals to respond to exercise. These pathways provides potential targets for identification of logical interventions that may help maintain muscle mass and function during ageing.

GABA Prevents Sarcopenia by Regulation of Muscle Protein Degradation and Inflammaging in 23- to 25-Month-Old Female Mice.

Sarcopenia is the gradual decrease in skeletal muscle mass, strength and function in elderly individuals. Gamma-aminobutyric acid (GABA) is a neurotransmitter naturally produced from glutamate by the enzyme glutamic acid decarboxylase. Age-related decline in GABA is linked to age-related motor and sensory decline and seems to affect sarcopenia, yet no detailed study has been conducted. In this study, we aimed to investigate the effect of GABA on improving sarcopenia by suppressing muscle protein degradation through supplementing decreased GABA in old mice. GABA (10 or 30 mg/kg/day) was orally administered daily to young (3 months) and old (21-23 months) C57BL/6 mice for 7 weeks. The body weight and grip strength of the mice were measured weekly at the same time. After sacrificing the mice, the quadriceps and gastrocnemius muscles were excised from their hind limbs, and the spleen and serum were collected. Histological, biochemical and molecular analyses were conducted in various experiments. The administration of GABA increased muscle strength (+41%, +70% compared to the aged mouse control group, GABA at doses of 10 or 30 mg/kg/day respectively, p < 0.05) and muscle mass (quadriceps: +28%, +46%; gastrocnemius: +12%, +19%, p < 0.05) in old mice. This increase was accompanied by a cross-sectional area (CSA) increase in the quadriceps and gastrocnemius muscle (p < 0.05). The administration of GABA increased IGF-1 levels in serum (p < 0.05), leading to the activation of muscle protein synthesis. We found that GABA inhibits sarcopenia by regulating muscle protein degradation through the activation of Akt/mTOR/FoxO3a signalling pathways. GABA also regulates inflammaging, which is a hallmark of age-related muscle atrophy. There was a significant increase in the F4/80 + CD11b + total macrophage ratio in gastrocnemius and spleen, especially the M1 macrophage ratio increased in old mice. However, GABA administration was effective in suppressing M1 macrophages (gastrocnemius: -40%, - 53%; spleen: -22%, -26%, p < 0.05). Pro-inflammatory cytokines such as TNF-α and IL-6, primarily secreted by M1 macrophages, are also decreased by treatment with GABA (TNF-α: -24%, -27%; IL-6: -45%, -59%, p < 0.05). Together, this study demonstrates the importance of GABA in maintaining muscle and low-chronic inflammation during ageing. We suggest that GABA shows potential as a substance that can effectively address sarcopenia and enhance the overall lifespan and well-being of older individuals.

Development and initial validation of the Cognitive Change Scale (CCS).

Cognitive impairment is common in neurologic diseases. Precise measurement of cognitive change over time is necessary for isolating disease-related patterns from normal age-related decline. Existing measures of subjective cognition, however, focus on present status. There is, to our knowledge, no currently available self-report measure of cognitive change. We therefore developed the Cognitive Change Scale (CCS), which assesses perceived cognitive change in neurologic populations. A systematic mixed-methods process was followed for the scale design and validation. Associations of CCS responses to demographics, mood, and fatigue were examined in 131 persons with multiple sclerosis. A total of 46 participants also completed a cognitive test battery. Correlations of test scores with CCS responses were calculated. The 17-item CCS showed good reliability and validity. Results of exploratory and confirmatory factor analyses supported a four-factor structure, with items reflecting change in (1) general cognition, (2) language and executive function, (3) external feedback, and (4) use of coping strategies. Positive relationships of CCS scores with fatigue, depression, and anxiety were observed. Correlations of CCS scores with cognitive test performance did not reach significance. The CCS may be a useful cognitive outcome tool for treatment trials in neurologic populations.

Accumulation of advanced oxidation protein products promotes age-related decline of type H vessels in bone.

Type H vessels have been proven to couple angiogenesis and osteogenesis. The decline of type H vessels contributes to bone loss in the aging process. Aging is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, whether AOPP accumulation is involved in age-related decline of type H vessels is unclear. Here, we show that the increase of AOPP levels in plasma and bone were correlated with the decline of type H vessels and loss of bone mass in old mice. Exposure of microvascular endothelial cells to AOPPs significantly inhibited cell proliferation, migration, and tube formation, increased NADPH oxidase activity and excessive reactive oxygen species generation, upregulated the expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1, and eventually impaired angiogenesis, which was alleviated by redox modulator N-acetylcysteine and NADPH oxidase inhibitor apocynin. Furthermore, reduced AOPP accumulation by NAC treatment was able to alleviate significantly the decline of type H vessels, bone mass loss and deterioration of bone microstructure in old mice. Collectively, these findings suggest that AOPPs accumulation contributes to the decline of type H vessels in the aging process, and illuminate a novel potential mechanism underlying age-related bone loss.

Behavioural and neuronal substrates of serious game-based computerised cognitive training in cognitive decline: randomised controlled trial.

Investigations of computerised cognitive training (CCT) show heterogeneous results in slowing age-related cognitive decline. To comprehensively evaluate the effectiveness of serious games-based CCT, integrating control conditions, neurophysiological and blood-based biomarkers, and subjective measures. In this bi-centric randomised controlled trial with parallel groups, 160 participants (mean age 71.3 years) with cognitive impairment ranging from subjective decline to mild cognitive impairment, were pseudo-randomised to three arms: an intervention group receiving CCT immediately, an active control (watching documentaries) and a waitlist condition, which both started the CCT intervention after the control period. Both active arms entailed a 3-month intervention period comprising a total of 60 at-home sessions (five per week) and weekly on-site group meetings. In the intervention group, this was followed by additional 6 months of CCT, with monthly booster sessions to assess long-term training effects. Behavioural and subjective changes were assessed in 3-month intervals. Biological effects were measured by amyloid blood markers and magnetic resonance imaging obtained before and after training. Adherence to the training protocol was consistently high across groups and time points (4.87 sessions per week). Domain-specific cognitive scores showed no significant interaction between groups and time points. Significant cognitive and subjective improvements were observed after long-term training. Voxel-based morphometry revealed no significant changes in grey matter volume following CCT, nor did amyloid levels moderate its effectiveness. Our study demonstrates no benefits of 3 months of CCT on cognitive or biological outcomes. However, positive effects were observed subjectively and after long-term CCT, warranting the inclusion of CCT in multicomponent interventions.

Association Analysis of Telomere Length and Vision in a Large Community-Based Survey

ABSTRACT Purpose To investigate whether there is a direct, age-independent association between telomere length and visual acuity decline in a large community-based cohort study. Methods Participants older than 40 with linked leukocyte telomere length (LTL) were enrolled in NHANES. LTL was assayed using qPCR from the participants’ blood samples. Best corrected visual acuity (BCVA) of the better-seeing eye was analyzed, with visual impairment (VI) defined as BCVA ≥ 20/40. LTL was grouped into quartiles, and its association with BCVA and VI was evaluated after adjusting for covariates. Results Among the 4,480 enrolled participants, the weighted means of age, BCVA, and telomere length were 56.1 ± 11.9 years, 0.05 ± 0.08 logMAR, and 5,662 ± 36 base pairs, respectively. The proportion of VI was 2.6%. After adjusting for covariates including sex, ethnicity, education, family poverty income ratio, general health status, hypertension, diabetes, smoking, and body mass index, BCVA was significantly worse in participants with shorter LTL, with a significant trend (p = 0.002). However, after further adjusting for age, the association between LTL and BCVA was no longer significant, without a trend (p = 0.640). No significant association or trend between LTL and VI was found in the stepwise logistic model. Conclusions No age-independent association between LTL and BCVA was found. Our study indicates LTL may not serve as a biomarker for age-related visual acuity decline.

Dentists' perceptions of providing care to community-dwelling older people.

This study explored the attitudes of New Zealand (NZ) general dental practitioners (GDPs) towards older adults living within the community and the barriers and difficulties caring for their oral health needs. Adults are living longer and retaining teeth. Their dentitions are complex and alongside their dental needs, older adults often experience age-related systemic disease or decline. Ageism and stereotypical views of older adults impedes access to dental care. While there is some understanding of older adults and ageism from the perspective of dental students, there is a paucity of knowledge about dentists' management of this patient demographic. A mixed-methods survey questionnaire collected quantitative and qualitative data. Quantitative data were analysed descriptively followed by bivariate analysis. Qualitative data responses to open-ended questions were analysed thematically. A total of 382 GDPs participated (response rate of 24%) and demonstrated positive attitudes and low levels of ageism towards older adults who they enjoyed treating. Confidence was positively related to clinical experience, and most dentists had engaged in gerodontology updates. Barriers to care for older adults were perceived to be beyond their control and mostly related to cost, chronic disease or age-related change. Consent processes could create difficulty and so collaboration with family or caregivers was important. The GDPs displayed positive attitudes and confidence towards older adults who are a rewarding patient cohort. Gerodontology education during training and following graduation is critical to enhance oral health outcomes for older patients.

Life Satisfaction Among Adolescents: Validation of the Adapted Multidimensional Students’ Life Satisfaction Scale

Life satisfaction is associated with adolescents’ adaptability, academic achievement, and mental health, and it reflects the profile of a country’s economic development. In this study, we assessed the psychometric properties of the Russian version of the Multidimensional Students’ Life Satisfaction Scale (MSLSS). The initial adaptation of the MSLSS was performed using a sample of primary school students. Validation on a sample of early-to-middle adolescents is necessary to assess its reliability and validity for this age group. The sample comprised 2826 adolescents between ages 10 and 16 (Mage = 12.6, SD = 1.2, 41.3% girls) who completed the Russian version of the MSLSS assessing their perceived life satisfaction across five scales. While the five-factor structure of the MSLSS was confirmed, the psychometric analysis indicated that the statements function more effectively measured life satisfaction as a singular one-factor construct. We also observed a significant age-related decline in overall life satisfaction and satisfaction with family, self, school, friends, and teachers. Boys reported significantly lower satisfaction with school compared to girls. This study confirms the validity and reliability of the Russian version of the MSLSS, thereby augmenting its general applicability. Furthermore, we replicated previously reported age and gender differences in life satisfaction among early-to-middle adolescents.

Age-related decline in blood-brain barrier function is more pronounced in males than females in parietal and temporal regions.

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60 s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.

Increased DNMT1 acetylation leads to global DNA methylation suppression in follicular granulosa cells during reproductive aging in mammals

With increasing age, the reproductive performance of women and female animals declines. However, the molecular mechanisms underlying ovarian aging and age-related fertility decline remain unclear. Granulosa cells (GCs) are suspected to play an important role in reproductive aging, and their proliferation, apoptosis, and steroid hormone secretion are used to determine the fate of follicles and ovarian function. First, we found that the proliferative ability of GCs from the old mouse group (10-month-old) decreased compared with that from the young mouse group (6-week-old), and cell cycle arrest occurred in old mice. To investigate changes in protein modification, we compared the levels of protein acetylation in GCs from young and old mice. We found that the K1118, K1120, K1122, and K1124 sites of DNA methyltransferase 1 (DNMT1) were increasingly acetylated with age, resulting in a decrease in DNMT1 protein expression. Therefore, we performed whole-genome methylation sequencing of GCs in the two groups and found that the CG methylation levels in the old group were lower than those in the young group. Furthermore, the inhibition of DNMT1 expression in GCs resulted in cell cycle arrest. This study revealed the dynamics and importance of protein acetylation and DNA methylation in GCs during reproductive aging. The findings provide a theoretical basis for studying the mechanism of reproductive aging in mammals.

Category-Sensitive Age-Related Shifts Between Prosodic and Semantic Dominance in Emotion Perception Linked to Cognitive Capacities.

Prior research extensively documented challenges in recognizing verbal and nonverbal emotion among older individuals when compared with younger counterparts. However, the nature of these age-related changes remains unclear. The present study investigated how older and younger adults comprehend four basic emotions (i.e., anger, happiness, neutrality, and sadness) conveyed through verbal (semantic) and nonverbal (facial and prosodic) channels. A total of 73 older adults (43 women, Mage = 70.18 years) and 74 younger adults (37 women, Mage = 22.01 years) partook in a fixed-choice test for recognizing emotions presented visually via facial expressions or auditorily through prosody or semantics. The results confirmed age-related decline in recognizing emotions across all channels except for identifying happy facial expressions. Furthermore, the two age groups demonstrated both commonalities and disparities in their inclinations toward specific channels. While both groups displayed a shared dominance of visual facial cues over auditory emotional signals, older adults indicated a preference for semantics, whereas younger adults displayed a preference for prosody in auditory emotion perception. Notably, the dominance effects observed in older adults for visual and semantic cues were less pronounced for sadness and anger compared to other emotions. These challenges in emotion recognition and the shifts in channel preferences among older adults were correlated with their general cognitive capabilities. Together, the findings underscore that age-related obstacles in perceiving emotions and alterations in channel dominance, which vary by emotional category, are significantly intertwined with overall cognitive functioning. https://doi.org/10.23641/asha.27307251.

Cannabis Use and Age-Related Changes in Cognitive Function From Early Adulthood to Late Midlife in 5162 Danish Men.

Cannabis is by far the most widely used and abused drug listed on the Drug Enforcement Administration's Schedule I, which includes drugs with a high potential for abuse. There is evidence of short-term negative effects of cannabis use on cognition, but only a limited number of studies have explored the association between cannabis use and age-related cognitive decline. The aim of the present study was to investigate the relationship between cannabis use and age-related cognitive decline from early adulthood to late midlife. The study population consisted of 5162 men who had participated in Danish follow-up studies on cognitive aging. These studies included scores on the military intelligence test Børge Prien's Prøve from both the conscription assessment (mean age=20years; p1 and p99: 18 and 26years) and from the follow-up (mean age=64years; p1 and p99: 55 and 72years) as well as extensive data on lifestyle and health from the follow-up questionnaires. The association between cannabis use and age-related cognitive decline was investigated in linear regression models. Men with a history of cannabis use had less cognitive decline from early adulthood to late midlife compared to men without a history of cannabis use. Among cannabis users, neither age of initiation of cannabis use nor frequent use was significantly associated with a greater age-related cognitive decline. In a sample of more than 5000 men followed for a mean of 44years, we found no significant harmful effects of cannabis use on age-related cognitive decline.

Transcriptomic evidence of black soybean ethanolic extract and 2-aminobutyric acid in suppressing neuroinflammation and enhancing synaptic transmission

IntroductionRecently, the awareness of the beneficial utilization of natural bioactive compounds in treating neuroinflammation has gained particular attention. We aimed to understand the anti-neuroinflammatory effect of black soybeans (Glycine max (L.) Merr) ethanolic extract (BBEE) and its bioactive compound, 2-aminobutyric acid (2-AB), against LPS-induced SH-SY5Y cells. MethodCell viability and the optimum therapeutic dose were confirmed by MTT assay. We conducted a whole-transcriptomic analysis of BBEE and 2-AB in LPS-induced SH-SY5Y cells using microarray normalized with SST-RMA. DEGs were selected based on p-value < 0.05 and fold change > 2, and validated by RT-qPCR and immunocytochemical analyses. ResultsWe found that both BBEE and 2-AB down-regulated the expression of inflammatory cytokines IL6 and TNFA under LPS-induced conditions. This was also observed in the microarray data, showing downregulation of several inflammatory pathways, such as NF-kB, and IL6-JAK/STAT3-signaling pathways. In contrast, it upregulated the expression of CALML3, GRIN2, and GRIA2 gene expressions, which influence the AMPK and CAMK2 signaling pathways, indicating the potential of BBEE in neurotransmission and synaptic function. Also, immunofluorescence analysis revealed that 2-AB treatment significantly increased PSD-95 and Ca2+ levels, suggesting its effect on synaptic transmission essential for brain function. ConclusionOur findings suggest the potential anti-neuroinflammatory effects of BBEE and 2-AB, which may offer therapeutic and preventive benefits in mitigating neurological disorders. Given that BB is widely consumed in many Asian countries, our study may encourage its incorporation into the daily diet to slow inflammation-induced neurodegenerative disorders, reduce age-related cognitive decline, and enhance overall brain function.

Does concomitant diazepam and ethanol use modulate age-related cognitive decline in mice?

BackgroundConcomitant use of alcohol and benzodiazepines are described among elderly, raising concerns about their combined impact on memory. We aimed to evaluate the long-term impact of chronic diazepam use associated with ethanol intoxication on memory in aging mice. MethodsTwelve-month-old male C57BL6 mice were assigned into 4 groups: ethanol (OH), diazepam (DIA), diazepam + ethanol (DOH) and control (CTL). For 16 weeks, ethanol was available ad libitum and diazepam was mixed with food. Behavioral testing, performed during and after treatment cessation included working memory and visual recognition memory assessment. The second session was implemented with spatial reference learning and memory assessment in the Barnes maze test. In vivo magnetic resonance spectroscopy (MRS) acquisitions were performed to quantify hippocampal metabolites during and after cessation treatment. ResultsDuring treatment, visual recognition memory was significantly different between groups with the DIA group exhibiting the worst performance. MRS acquisition highlighted higher glutamate and choline levels in OH and DOH groups in comparison to CTL and DIA groups. After treatment wash-out, there was no difference between in the different memories evaluated. Only the learning phase of the spatial reference memory test differed significantly with worst performance in OH groups. Three months after treatment cessation, there was no remanent effect of diazepam + ethanol on hippocampal metabolites changes. ConclusionsWe did not evidence additive effect of ethanol and diazepam on memory and hippocampal metabolite levels. The disturbances observed during treatment were no remanent, highlighting the benefits of discontinuing these substances.

Benefits of an educational intervention on functional capacity in community-dwelling older adults with frailty phenotype: A randomized controlled trial

BackgroundThere is an urgent demand for nurses to expand their knowledge and skills in managing frailty in primary care. Frailty is a multifaceted condition that is prevalent among older adults and often leads to reduced functional capacity. Currently, there is a limited understanding of the effectiveness of educational interventions aimed at improving functional capacity among community-dwelling frail older adults in a primary care setting. ObjectiveThis study aimed to evaluate the impact of an educational program on functional capacity among pre-frail and frail older adults living in the community. DesignA 12-month, multicenter, randomized controlled trial. SettingsThe FRAGSALUD study was conducted across 14 healthcare centers situated within the regions of Cadiz and Malaga, Spain. ParticipantsA total of 199 frail/pre-frail community-dwelling older adults (74.2 ± 6.4 years). MethodsParticipants who met at least one Fried's criteria were assigned to either the control group (n = 90), which received usual healthcare assistance, or the intervention group (n = 109). The 6-month intervention comprised four group sessions and six telephone calls conducted by professional nurses, sport scientists, and nutritionists. This educational program focused on guidelines for physical activity, nutritional habits, cognition, and psychosocial well-being. Functional capacity was assessed using questionnaires for basic (Barthel Index) and instrumental (Lawton & Brody Scale) activities of daily living. All outcome measures were evaluated at baseline, immediately after the intervention (6-month), and six months after the intervention as a follow-up (12-month). Differences in functional capacity (Barthel Index and Lawton and Brody Scale scores) across the three time points were analyzed using Friedman's ANOVA, with Wilcoxon signed-rank test for pairwise comparisons. ResultsAt both 6-month and 12-month assessments, the control group showed a statistically significant decline in basic and instrumental activities of daily living compared to the intervention group, which maintained similar levels, preventing this age-related decline. ConclusionsThe educational intervention, designed for easy implementation within healthcare systems, especially for nurses, successfully maintained levels of functional capacity in basic and instrumental activities of daily living, while the control group experienced a decline in functional capacity during the 12-month follow-up. Thus, educational interventions are encouraged for preserving the functional independence of frail/pre-frail older adults living in the community. RegistrationThis trial was registered at ClinicalTrials.gov (Identifier: NCT05610605) and the first participant was registered in March 2022.Tweetable abstract: The FRAGSALUD educational intervention prevents the age-related decline in functional independence over 12 months in frail older adults.

Examining the health effects of public transport use on older adults: A systematic review

Background and aimPublic transport use has been linked to several health benefits in the general population and is crucial for older adults’ mobility, due to an age-related decline in physical and cognitive capacity and mobility, particularly the ability to use other modes of transport. The objective of this systematic review is to determine what is known about the physical and mental health outcomes of public transport use of older adults and to identify remaining gaps in the literature. MethodsFive electronic databases were searched in April 2023, and then updated in January 2024: Pubmed, Scopus, Web of Science, Ageline and Transport Research International Documentation (TRID). Included were studies that were in English, contained a measure of public transport use as exposure, and any health outcome, including mental or physical health, physical or cognitive function, morbidity, or mortality, among people aged ≥60 years. ResultsOf a total of 2247 unique records that were screened, the full text of 20 was assessed for eligibility and 11 were identified as eligible. Citation search identified two additional studies, amounting to a total of 13 included studies. Significant health outcomes described in assessed studies were decreased obesity and depressive symptoms, and to a lesser extent increased gait speed and cognitive function. ConclusionsInitial evidence suggests a positive impact of public transport use on obesity, depressive symptoms, gait and cognitive function, although available research was limited in context and methodology. Further research should focus on determining causality between public transport use and health, and be conducted in more diverse contexts. Transport and urban planners, as well as policymakers, should consider the implications of public transport on the health and independence of older adults.

Rebalance the Inhibitory System in the Elderly Brain: Influence of Balance Learning on GABAergic Inhibition and Functional Connectivity.

Aging involves complex processes that impact the structure, function, and metabolism of the human brain. Declines in both structural and functional integrity along with reduced local inhibitory tone in the motor areas, as indicated by reduced γ-aminobutyric acid (GABA) levels, are often associated with compromised motor performance in elderly adults. Using multimodal neuroimaging techniques including magnetic resonance spectroscopy (MRS), diffusion magnetic resonance imaging (MRI), functional MRI as well as transcranial magnetic stimulation to assess short-interval intracortical inhibition (SICI), this study explores whether these age-related changes can be mitigated by motor learning. The investigation focused on the effects of long-term balance learning (3 months) on intracortical inhibition, metabolism, structural, and functional connectivity in the cortical sensorimotor network among an elderly cohort. We found that after 3 months of balance learning, subjects significantly improved balance performance, upregulated sensorimotor cortical GABA levels and ventral sensorimotor network functional connectivity (VSN-FC) compared to a passive control group. Furthermore, correlation analysis suggested a positive association between baseline VSN-FC and balance performance, between baseline VSN-FC and SICI, and between improvements in balance performance and upregulation in SICI in the training group, though these correlations did not survive the false discovery rate correction. These findings demonstrate that balance learning has the potential to counteract aging-related decline in functional connectivity and cortical inhibition on the "tonic" (MRS) and "functional" (SICI) level and shed new light on the close interplay between the GABAergic system, functional connectivity, and behavior.

Changes in Gene Expression Profile with Age in SAMP8: Identifying Transcripts Involved in Cognitive Decline and Sporadic Alzheimer’s Disease

Background: The senescence-accelerated mouse 8 (SAMP8) represents a model for Alzheimer’s disease (AD) research because it exhibits age-related learning and memory impairments consistent with early onset and rapid progression of senescence. To identify transcriptional changes during AD progression, in this study, we analyzed and compared the gene expression profiles involved in molecular pathways of neurodegeneration and cognitive impairment in senescence-accelerated resistant 1 (SAMR1) and SAMP8 mice. Methods: In total, 48 female SAMR1 and SAMP8 mice were randomly divided into six groups (SAMR1 and SAMP8 at 3, 7, and 9 months of age). Microarray analysis of 22,000 genes was performed, followed by functional analysis using Gene Ontology (NCBI) and examination of altered molecular pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes). Results: SAMP8 mice had 2516 dysregulated transcripts at 3 months, 2549 transcripts at 7 months, and 2453 genes at 9 months compared to SAMR1 mice of the same age. These accounted for 11.3% of the total number. This showed that with age, the gene expression of downregulated transcripts increases, and that of over-expressed transcripts decreases. Most of these genes were involved in neurodegenerative metabolic pathways associated with Alzheimer’s disease: apoptosis, inflammatory response, oxidative stress, and mitochondria. The qPCR results indicated that Ndufs4, TST/Rhodanese, Wnt3, and Sema6a expression was differentially expressed during aging. Conclusions: These results further revealed significant differences in gene expression profiles at different ages between SAMR1 and SAMP8 and showed alteration in genes involved in age-related cognitive decline and mitochondrial processes, demonstrating the relevance of the SAMP8 model as a model for sporadic AD.