Frontiers in aging最新文献

Time shapes life both through its steady progression, as seen in aging, and through its eternal return, reflected in biological rhythms. These two temporal forces have sculpted organisms from their evolutionary beginnings, intertwining the processes of circadian regulation and senescence into the emerging concept of circadian aging. From the earliest prokaryotic lifeforms, the ability to sense and anticipate environmental cycles conferred evolutionary advantages, leading to the emergence of endogenous circadian clocks that regulate nearly every aspect of physiology. The mammalian circadian system is far more complex than a single master clock, comprising multiple tissue-specific oscillators entrained by diverse zeitgebers such as light, food, and activity. Importantly, circadian function deteriorates with age, contributing to hallmarks of aging including metabolic dysfunction, cognitive decline, immunosenescence, and disrupted sleep. Yet species with negligible senescence, such as naked mole-rats, tend to retain robust circadian rhythms throughout life, suggesting that temporal homeostasis may serve as both a marker and a modulator of healthy aging. This review explores the dynamic interplay between circadian time and chronological time, highlighting their shared regulatory pathways. We examine how circadian rhythms change naturally with age and in pathological conditions, the molecular crosstalk between clock genes and aging-related pathways and emerging evidence that circadian interventions can restore rhythmicity and promote healthspan. By unraveling the mechanisms of circadian aging, we aim to illuminate novel chrono-geroprotective strategies to enhance resilience and improve quality of life across the lifespan.

Background: Chronic pain, a major cause of disability, is prevalent in older people. Exposure to multiple adverse childhood experiences (ACEs) is associated with increased levels of chronic pain in later life. However, this association has not been investigated in people aged older than 80 years. Therefore, the primary objective of this study was to explore the relationship between ACEs and chronic pain in people with a mean age of 86 years, participants of the Lothian Birth Cohort 1936.

Methods: A survey co-developed by researchers, clinicians and people with lived experience (PWLE) that assessed chronic pain and ACEs was completed by 229 participants (response rate 67%). Associations between ACE exposure and chronic pain were investigated using multinomial logistic regression.

Results: Results showed that 58% reported chronic pain, with a higher prevalence in females. Furthermore, 69% of participants with chronic pain reported moderate or severe pain interference and 82% reported at least 1 ACE, with 25% indicating exposure to ≥4 ACEs. The most frequently reported exposure was community violence (48%). Males were more likely to report any ACE, physical neglect, bullying, and community violence. No significant association was found between ACEs and chronic pain status, severity, or interference in this cohort.

Discussion: This study, the first to adapt ACE and chronic pain questionnaires with input from PWLE, suggests that the relationship between ACEs and chronic pain may be less relevant in people in their eighties compared to younger populations. These findings have implications for trauma-informed care and pharmacological treatment in older adults.

It seems likely that the growing number of older adults and increasing urbanization will be among the most significant demographic and societal trends in the near future. These two global phenomena will undoubtedly have a profound effect on the demographic and geographical makeup of our world. In view of these changes, it is crucial that the health and social sciences consider how the concept of Aging in Place could play a valuable role in longevity studies. Considering this topic as correlated to different important themes such as functional, symbolic, and emotional attachment and importance of homes, neighborhoods, and communities - resumed in the categories of people, place and time - we introduce a new perspective in Aging in (urban) Place studies from a psychological perspective based on situated and embodied cognition, with the purpose of deeply analyzing the thin space between people and their context, viewing place not as a neutral backdrop but as a continuous opportunity for individuals to act. Only through an analysis of urban spaces as limits or possibilities in everyday life can we grasp how the city can be an adequate place to empower individuals' healthy longevity.

Unintentional falls are the leading cause of injury in adults ≥65 years. While causes of falls are multifactorial, weakness or disuse of the intrinsic foot muscles (IFM) can contribute. The purpose of this randomized controlled trial, using an effectiveness-implementation hybrid design, is to analyze the effects of two IFM strengthening interventions (minimal footwear use or strengthening exercises) on IFM size, proprioception, foot structure, and fall risk in older adults. Adults ages ≥65 years, with fall risk, who can ambulate household distances (with an assistive device as needed), will be invited to participate. Individuals with poor foot sensation, vestibular disorders, lower extremity amputation, lower extremity or lumbar spine injury or surgery in the previous 6 months, impaired cognitive ability to follow verbal and written instructions, and those who have participated in a fall prevention program in the past 6 months will be excluded. Participants will be randomly allocated into three groups: prescribed minimal footwear use, IFM strengthening exercises, or control. Participants will be encouraged to perform their intervention 5 days per week for 16 weeks, and then at least 2 days per week from 17 weeks to 1 year. Participants will be asked to record intervention performance, daily step count, and falls in provided diaries. At baseline, 8 and 16 weeks, and 1 year, participants will undergo measurements of IFM cross-sectional area (CSA, cm²) using ultrasound imaging, proprioception, foot structure (navicular drop and hallux valgus angle) and fall risk. Semi-structured interviews will be conducted and recorded to gain participant impressions of the interventions, self-reported effects of the interventions, and impressions of study activities to inform future research and clinical implementation. A three-group x four time point repeated measures analysis of covariance will be used to assess changes in measurements. Implementation data will be analyzed using both quantitative and qualitative methods. This will be the first study among older adults to assess the effects of IFM strengthening interventions on long-term fall risk and proprioception, and to use ultrasound imaging to assess IFM size changes. These interventions are simple, safe, and affordable and may have a major impact on functional mobility and reduction of falls for older adults.

Background: Individuals undergoing lung cancer surgery often face significant postoperative challenges, underscoring the importance of identifying effective preoperative rehabilitation strategies to support recovery.

Aim: To identify rehabilitation interventions that can be implemented during the preoperative period for individuals with lung cancer undergoing thoracic surgery.

Design: Scoping review guided by the Arksey and O'Malley methodological framework.

Methods: The research question guiding this review was "What rehabilitation interventions should be implemented in the preoperative period for individuals with lung cancer undergoing surgery?" A comprehensive search was performed across five databases: MEDLINE, Cochrane Central, CINAHL, ScienceDirect, and PubMed. The review included studies that addressed rehabilitation interventions before thoracic surgery for individuals with lung cancer.

Results: A total of 19 articles met the inclusion criteria. The findings indicate that combining aerobic endurance, resistance, and respiratory training with preoperative education improves outcomes. In addition, nutritional counseling and brief relaxation/emotion-regulation strategies appear to be valuable components of multimodal prehabilitation programs, though evidence is limited.

Conclusion: Preoperative rehabilitation interventions have the potential to enhance functional reserve, reduce postoperative complications, and accelerate recovery in individuals undergoing lung resection for lung cancer.

Mesenchymal stem cells (MSCs) exhibit self-renewal and multipotent differentiation capabilities, and play roles in tissue repair and regeneration. However, age-related alterations can impair MSCs functions, potentially contributing to accelerated aging processes. Ferroptosis, a regulated form of cell death involving iron-mediated lipid peroxidation, is implicated in age-related diseases, although its specific role in MSCs aging remains unclear. Herein, the GSE68374 dataset was analyzed to obtain ferroptosis-related differentially expressed genes (FRDEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed, and potential drugs targeting FRDEGs were predicted. Protein-protein interaction (PPI) analysis was conducted and hub genes were identified, which were validated using two independent datasets. Furthermore, an integrated regulatory network of kinases, transcription factors (TFs), and microRNAs was constructed. A total of 131 FRDEGs were screened, which were involved in cellular responses to starvation, oxidative stress, lipid metabolism, cellular senescence, ferroptosis, and cancer pathways. Among twenty hub genes, eight key FRDEGs, including activating transcription factor 3 (ATF3), Enhancer of zeste homolog 2 (EZH2), synuclein alpha (SNCA), prostaglandin-endoperoxide synthase 2 (PTGS2), NADPH oxidase 4 (NOX4), cyclin-dependent kinase inhibitor 2A (CDKN2A), sequestosome 1 (SQSTM1), and interleukin 6 (IL6), were similarly regulated across external datasets, and the expression of these genes was also confirmed by qRT-PCR. These findings highlight the pivotal role of these genes in MSCs aging and ferroptosis, suggesting that targeting them could enhance MSCs regenerative capacity and mitigate the progression of aging-related alterations in MSCs.

Population aging will be on the public health agenda in the coming decades. By 2050, 16% of the world's population will be aged 65 and above, mostly living in middle- and low-income countries. In Brazil, the aged population will triple by 2050, from less than 20 million to approximately 65 million, making it the sixth largest aged population in the world. Population aging is associated with an increase in the prevalence of chronic non-communicable diseases, which in turn promotes a functional decline in people who age. This often leads to limitations in daily life and dependence, with clear implications for the quality of life and health costs. In 2015, the World Health Organization proposed the concept of intrinsic capacity (IC) as a multidimensional health indicator that encompasses the essential physical and mental capabilities for people to perform what they need and like in daily life, regardless of the chronological age. In practice, IC was operationalized in five health domains, namely, cognitive, psychological, sensory, locomotor, and vitality. These domains, which are evaluated together and over time, offer the function parameters necessary to understand different, person-centered aging trajectories. Prevention of age-associated functional decline has not been studied well. Literature lacks studies that indicate the expected values for different IC trajectories related to aging, with or without disability. Few studies have analyzed IC as a risk factor for compromising the functional ability (FA) of the elderly, which is measured by the degree of dependence in activities of daily living, the risk of falls, and early mortality, while controlling for all known risk factors for functional decline. The cohort study proposed here, called "Longevity with Functionality (LONGFUN)," addresses the growing importance of evaluating the indicators of IC in a prospective way, creating a single indicator, and relating it to the FA of the aged population.

Abstract: Alzheimer's disease (AD), the most commonly diagnosed form of senile dementia worldwide, is closely associated with aging and distinct neuropathological features. Recent studies highlight that up to 90% of individuals, either preclinical or clinical, diagnosed with vascular pathology in the context of AD exhibit thickening and hyalinization of the media in small and medium-sized cerebral vessels. Exercise has emerged as a potential, non-pharmaceutical, and cost-effective intervention for the prevention and treatment of AD. However, there is limited research exploring the effects of high-intensity interval training (HIIT) on cerebrovascular function in AD.

Methods: Four-month-old female C57BL/6 J mice and APP/PS1 transgenic mice were initially acclimated to a standard diet for 1 week. The two groups were then divided into sedentary and exercise cohorts, with the exercise group engaging in a 6-week HIIT regimen. Post-intervention, hippocampal specimens were collected for analysis. Aβ and Tau protein levels were measured to assess AD pathology, while cognitive function was evaluated using the eight-arm radial maze and BDNF mRNA expression. Additionally, markers of cerebrovascular function-including VEGF, EPO, eNOS, GPR68, and ET-1-were examined, and HIF-1α was utilized to assess the hippocampal response to AD pathology.

Results: HIIT significantly reduced reference memory errors (p = 0.025) and markedly upregulated Bdnf mRNA expression (p < 0.001) specifically in APP/PS1 mice. Furthermore, HIIT significantly decreased protein levels of AD pathological markers p-TAU (p = 0.001) and APP (p = 0.002) in APP/PS1 mice. HIIT significantly increased the mRNA (p < 0.001) and protein (p = 0.003) levels of EPO and Vegfa mRNA (p < 0.001) levels to stimulate pro-angiogenic signal in APP/PS1 mice. HIIT also significantly increased both the mRNA and proteins levels of eNOS expression (p < 0.001) while decreasing the mRNA and proteins levels of ET-1 (p < 0.001) and GPR68 (p < 0.001) to enhance vasodilation in APP/PS1 mice. Finally, HIIT significantly increased HIF-1α expression at both protein and mRNA levels (p < 0.001), independent of genotype.

Conclusion: HIIT ameliorates cognitive function and reduces hallmark AD pathology. This positive effect is potentially mediated through cerebral microangiogenesis, cerebrovascular function regulation, and hypoxic metabolism. HIIT represents a promising non-pharmacological strategy for targeting multiple aspects of AD pathophysiology.

Allogeneic hematopoietic cell transplantation (HCT) is often the only curative therapy for hematologic malignancies. Immune suppression is necessary for the engraftment of donor cells and prevention of graft-versus-host disease (GVHD). mTOR inhibitors like sirolimus are commonly used for GVHD prophylaxis. Low doses of sirolimus have demonstrated a gerotherapeutic effect, extending lifespan in animals, reducing senescent cell burden, and improving immune function in animals and humans. We hypothesized that the use of sirolimus in GVHD prophylaxis platforms, even at high doses, could have a senotherapeutic effect. We compared senescent cell burden in double umbilical cord blood HCT recipients with available baseline, day 100 and 365 post-HCT samples. All patients received an identical conditioning regimen with different GVHD prophylaxis: sirolimus + mycophenolate mofetil (MMF) or cyclosporine + MMF. At target doses to reduce GVHD risk, neither expression of senescence markers nor the abundance of SASP factors differed significantly in the sirolimus treated cohort compared to cyclosporine control cohort. However, we note a non-significant but perhaps biologically relevant trend of lower relative expression of p16 ^INK4a and p21 ^CIP1 post-HCT in the sirolimus cohort. Further longitudinal analysis including a larger cohort would be useful to determine the true magnitude of differences in senescent cell burden. Our results suggest that the daily administration and dosing used for GVHD prevention are less likely to confer clinical benefits, possibly indicating that the beneficial effects of sirolimus occur within a specific therapeutic window. These findings highlight the need to further investigate senotherapeutic approaches in this setting of accelerated aging.