Frontiers in aging最新文献

Overweight, defined by a body mass index (BMI) between 25 and 30, has been associated with enhanced survival among older adults in some studies. However, whether being overweight is causally linked to longevity remains unclear. To investigate this, we conducted a Mendelian randomization (MR) study of lifespan 85+ years, using overweight as an exposure variable and data from the Health and Retirement Study and the Long Life Family Study. An essential aspect of MR involves selecting appropriate single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). This is challenging due to the limited number of SNP candidates within biologically relevant genes that can satisfy all necessary assumptions and criteria. To address this challenge, we employed a novel strategy of creating additional IVs by pairing SNPs between candidate genes. This strategy allowed us to expand the pool of IV candidates with new "composite" SNPs derived from eight candidate obesity genes. Our study found that being overweight between ages 75 and 85, compared to having a normal weight (BMI 18.5-24.9), significantly contributes to improved survival beyond age 85. Results of this MR study thus support a causal relationship between overweight and longevity in older adults.

Aging is a universal and progressive process involving the deterioration of physiological functions and the accumulation of cellular damage. Gene regulation programs influence how phenotypes respond to environmental and intrinsic changes during aging. Although several factors, including sex, are known to impact this process, the underlying mechanisms remain incompletely understood. Here, we investigate the functional organization patterns of skeletal muscle genes across different sexes and ages using gene co-expression networks (GCNs) to explore their influence on aging. We constructed GCNs for three different age groups for male and female samples, analyzed topological similarities and differences, inferred significant associated processes for each network, and constructed null models to provide statistically robust results. We found that each network is topologically and functionally distinct, with young women having the most associated processes, likely due to reproductive tasks. The functional organization and modularity of genes decline with age, starting from middle age, potentially leading to age-related deterioration. Women maintain better gene functional organization throughout life compared to men, especially in processes like macroautophagy and sarcomere organization. The study suggests that the loss of gene co-expression could be a universal aging marker. This research offers insights into how gene organization changes with age and sex, providing a complementary method to analyze aging.

Chronic pain is a debilitating condition frequently observed in the elderly, involving numerous pathological mechanisms within the nervous system. Diminished local blood flow, nerve degeneration, variations in fiber composition, alterations in ion channels and receptors, accompanied by the sustained activation of immune cells and release of pro-inflammatory cytokines, lead to overactivation of the peripheral nervous system. In the central nervous system, chronic pain is strongly associated with the activation of glial cells, which results in central sensitization and increased pain perception. Moreover, age-related alterations in neural plasticity and disruptions in pain inhibitory pathways can exacerbate chronic pain in older adults. Finally, the environmental influences on the development of chronic pain in the elderly must be considered. An understanding of these mechanisms is essential for developing novel treatments for chronic pain, which can significantly improve the quality of life for this vulnerable population.

The function of General Control Nonderepressible 2 (GCN2), an evolutionary-conserved component of the integrated stress response (ISR), has been well-documented across organisms from yeast to mammals. Recently GCN2 has also gained attention for its role in health and disease states. In this review, we provide a brief overview of GCN2, including its structure, activation mechanisms and interacting partners, and explore its potential significance as a therapeutic target in various age-related diseases including neurodegeneration, inflammatory disorders and cancer. Finally, we summarize the barriers to effectively targeting GCN2 for the treatment of disease and to promote a healthier aging process.

Despite extensive research into extending human healthspan (HS) and compressing morbidity, the mechanisms underlying aging remain elusive. However, a better understanding of the genetic advantages responsible for the exceptional HS of healthy centenarians (HC), who live in good physical and mental health for one hundred or more years, could lead to innovative health-extending strategies. This review explores the role of NLRP3, a critical component of innate immunity that significantly impacts aging. It is activated by pathogen-associated signals and self-derived signals that increase with age, leading to low-grade inflammation implicated in age-related diseases. Furthermore, NLRP3 functions upstream in several molecular aging pathways, regulates cellular senescence, and may underlie the robust health observed in HC. By targeting NLRP3, mice exhibit a phenotype akin to that of HC, the HS of monkeys is extended, and aging symptoms are reversed in humans. Thus, targeting NLRP3 could offer a promising approach to extend HS. Additionally, a paradigm shift is proposed. Given that the HS of the broader population is 30 years shorter than that of HC, it is postulated that they suffer from a form of accelerated aging. The term 'auto-aging' is suggested to describe accelerated aging driven by NLRP3.

Cellular senescence is a diverse phenotype characterised by permanent cell cycle arrest and an associated secretory phenotype (SASP) which includes inflammatory cytokines. Typically, senescent cells are removed by the immune system, but this process becomes dysregulated with age causing senescent cells to accumulate and induce chronic inflammatory signalling. Identifying senescent cells is challenging due to senescence phenotype heterogeneity, and senotherapy often requires a combinatorial approach. Here we systematically collected 119 transcriptomic datasets related to human fibroblasts, forming an online database describing the relevant variables for each study allowing users to filter for variables and genes of interest. Our own analysis of the database identified 28 genes significantly up- or downregulated across four senescence types (DNA damage induced senescence (DDIS), oncogene induced senescence (OIS), replicative senescence, and bystander induced senescence) compared to proliferating controls. We also found gene expression patterns of conventional senescence markers were highly specific and reliable for different senescence inducers, cell lines, and timepoints. Our comprehensive data supported several observations made in existing studies using single datasets, including stronger p53 signalling in DDIS compared to OIS. However, contrary to some early observations, both p16 and p21 mRNA levels rise quickly, depending on senescence type, and persist for at least 8-11 days. Additionally, little evidence was found to support an initial TGFβ-centric SASP. To support our transcriptomic analysis, we computationally modelled temporal protein changes of select core senescence proteins during DDIS and OIS, as well as perform knockdown interventions. We conclude that while universal biomarkers of senescence are difficult to identify, conventional senescence markers follow predictable profiles and construction of a framework for studying senescence could lead to more reproducible data and understanding of senescence heterogeneity.

Background: The aging population in Poland poses significant challenges to social and health systems. By 2050, the percentage of people over 65 in Poland is projected to reach 32.7%. Promoting physical activity among seniors is crucial for preventing chronic diseases, improving quality of life, and reducing healthcare burdens. Local governments play a pivotal role in implementing health-promoting measures.

Objective: The study aims to analyze seniors' satisfaction with local government activities in promoting physical activity and to identify the best activities and future needs of seniors in the Silesia, Mazovia, and Pomerania regions of Poland.

Material and methods: The survey, conducted between May 2023 and May 2024, utilized the Computer Assisted Web Interviewing (CAWI) method to gather data from 1,500 seniors aged 65 and above across the Silesia, Mazovia, and Pomerania regions. The study population was carefully selected to ensure representativeness in terms of gender, age, education, and place of residence. Data analysis included chi-square tests and logistic regression to assess satisfaction levels and identify influencing factors.

Results: The survey revealed regional differences in satisfaction levels. Seniors in the Mazovia region exhibited the highest satisfaction (74% positive ratings), followed by the Silesian (64%) and Pomeranian (56%) regions. Factors influencing satisfaction included gender, age, education, and place of residence. Women, older seniors, those with higher education, and urban residents reported higher satisfaction levels. The most appreciated local government activities were related to sports infrastructure and sports programs. Future needs emphasized the demand for more sports programs and better infrastructure, with regional variations in preferences.

Conclusion: Seniors' satisfaction with local government activities in promoting physical activity varies significantly across regions. Tailoring activities to regional preferences and continuous evaluation of programs are essential for enhancing effectiveness and satisfaction. Increased funding and support for physical activity programs are necessary, especially in less developed regions.

In this paper, we measured B cell function in elderly healthy individuals (E_H) and in elderly patients with Type-2 Diabetes Mellitus (T2DM, E_T2DM), which are treatment-naive, as compared to healthy young (Y_H) individuals. Results show a higher serum inflammatory status of elderly versus young individuals, and especially of E_T2DM versus E_H. This status is associated with a reduced response to the seasonal influenza vaccine and with increased frequencies of the circulating pro-inflammatory B cell subset called Double Negative (DN) B cells. B cells from E_T2DM patients are not only more inflammatory but also hyper-metabolic as compared to those from E_H controls. The results herein are to our knowledge the first to show that T2DM superimposed on aging further increases systemic and B cell intrinsic inflammation, as well as dysfunctional humoral immunity. Our findings confirm and extend our previously published findings showing that inflammatory B cells are metabolically supported.

This study aimed to identify differences among body mass index (BMI) categories of older family caregivers (≥60 years) and their care recipients (≥65 years). Secondly, this study aimed to examine group differences and factors associated with weight change during a nutrition and oral health intervention. This secondary analysis of a randomized controlled trial (ClinicalTrial.gov (NCT04003493)) involved individually tailored nutritional guidance from a clinical nutritionist and oral health guidance from a dental hygienist. Baseline BMI differences were analyzed, followed by further analyses of group differences and associated factors of weight change over a 6-month period using generalized estimating equations. Among the participants (113 family caregivers and 107 care recipients), 36.3% and 35.1% were overweight (BMI >29 kg/m²), while 18.6% and 21.6% were underweight (BMI <24 kg/m²) at baseline, respectively. For family caregivers differences in BMI categories included age, mid-arm and calf circumferences, and plasma prealbumin concentration. For care recipients differences were observed in medication use, mid-arm and calf circumferences, Mini Nutritional Assessment scores, physical function, and number of teeth. During the 6-month intervention, there were no differences in weight change between intervention and control groups for both caregivers and care recipients. Factors significantly associated (p < 0.05) with weight loss included female sex for both caregivers and care recipients, and frailty for caregivers. Family caregivers' characteristics were not significantly associated with weight change in their care recipients. In conclusion, being overweight is a prevalent among older family caregivers and care recipients. Factors such as age, medication use, physical function, number of teeth, and Mini Nutritional Assessment scores varied across BMI categories. Female sex was associated with weight loss in both older family caregivers and care recipients, and frailty was associated with weight loss in caregivers. However, the characteristics of family caregivers did not explain the weight loss of their care recipients. Clinical Trial Registration: [https://www.ClinicalTrial.gov/], identifier [NCT04003493].