npj aging最新文献

Over the past five years, systemic NAD⁺ (nicotinamide adenine dinucleotide) decline has been accepted to be a key driving force of aging in the field of aging research. The original version of the NAD World concept was proposed in 2009, providing an integrated view of the NAD⁺-centric, systemic regulatory network for mammalian aging and longevity control. The reformulated version of the concept, the NAD World 2.0, was then proposed in 2016, emphasizing the importance of the inter-tissue communications between the hypothalamus and peripheral tissues including adipose tissue and skeletal muscle. There has been significant progress in our understanding of the importance of nicotinamide mononucleotide (NMN), a key NAD⁺ intermediate, and nicotinamide phosphoribosyltransferase (NAMPT), particularly extracellular NAMPT (eNAMPT). With these exciting developments, the further reformulated version of the concept, the NAD World 3.0, is now proposed, featuring multi-layered feedback loops mediated by NMN and eNAMPT for mammalian aging and longevity control.

Objective and subjective aging indicators reflect diverse biological and psychosocial processes, yet their combined association with premature mortality remains underexplored. This study aimed to investigate the association between a multidomain framework of aging indicators and premature mortality, addressing gaps in understanding cumulative effects. We included 369,741 UK Biobank participants initially free of cardiovascular disease (CVD) and cancer, followed until December 31, 2022. Four indicators, hearing loss, tooth loss, falls and subjective aging, were counted, and their joint associations with all-cause and cause-specific premature mortality were analyzed using the Cox proportional hazard models. During a median follow-up of 13.74 years, we documented 22,934 premature mortality. Participants with all indicators had an 81% (95%CI: 59-107%), 96% (47-160%), 55% (26-91%), and 114% (73-165%) higher risk of all-cause, CVD, cancer, and other-cause premature mortality, respectively, compared to those without indicators. The associations were particularly elevated among younger participants, those with unhealthy lifestyles, and those of lower socioeconomic status (P for interactions <0.05). Additive interaction with frailty contributed an additional 16.08% (7.91-24.25%) risk of premature mortality. Findings were replicated in the Health and Retirement Study, supporting the robustness of the multidomain aging framework. This study highlights the potential of integrating objective and subjective aging indicators to refine risk assessments and inform interventions targeting aging-related diseases.

We investigated clinical factors and biochemical markers associated with amygdalar metabolic activity evaluated by [¹⁸F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) in 346 subjects without a history of malignant neoplasms. Univariate regression analysis revealed significant relationships between amygdalar metabolic activity and fasting plasma glucose (FPG), glycated hemoglobin, coronary artery disease (CAD) history, aspirin use, oral hypoglycemic agents (OHAs) use, and asymmetric dimethylarginine (ADMA). In multiple stepwise regression analysis, FPG and CAD history were independently associated with amygdalar metabolic activity. Moreover, in 36 patients with type 2 diabetes mellitus (T2DM), additional OHAs treatment significantly improved glycemic and metabolic parameters, and decreased ADMA concentrations. Baseline and Δpigment epithelium-derived factor (PEDF), a marker of insulin resistance, was a significant associate with Δamygdalar metabolic activity. Our study demonstrates that FPG and CAD history were independently associated with amygdalar metabolic activity in subjects without a history of malignant neoplasms. In T2DM patients, PEDF might regulate amygdala metabolic activity.

Age-related declines in cardiac function and exercise tolerance interfere with healthy living and decrease healthy life expectancy in older individuals. Tamogi-take mushrooms (Pleurotus cornucopiae) are known to contain high levels of Ergothioneine (EGT), an antioxidant with potential health benefits. In this study, we assessed the possibility that long-term consumption of Tamogi-take mushrooms might attenuate age-related decline in cardiac and vascular endothelial function in mice. We found that long-term intake of Tamogi-take mushrooms significantly maintained cardiac and vascular endothelial function and improved exercise tolerance in mice. Long-term mushroom consumption also increased levels of Nrf2 (Nuclear factor E2-related factor 2) protein in heart tissues and increased translation of HO-1 (Heme Oxygenase 1) proteins, which have antioxidant effects in heart and aortic tissues. Finally, long-term Tamogi-take mushroom consumption inhibited ROS accumulation with aging and reduced expression of inflammatory biomarkers. We conclude that ingestion of Tamogi-take mushrooms could serve as a dietary intervention to promote cardiovascular health, support healthy aging and slow the progression of age-related diseases.

The development of anti-aging drugs is challenged by both the apparent complexity of the physiological mechanisms involved in aging and the likelihood that many of these mechanisms remain unknown. As a consequence, the development of anti-aging compounds based on the rational targeting of specific pathways has fallen short of the goal. To date, the most impressive compound is rapamycin, a natural bacterial product initially identified as an antifungal, and only subsequently discovered to have anti-aging properties. In this review, we focus on two aminosterols from the dogfish shark, Squalus acanthias, that we discovered initially as broad-spectrum anti-microbial agents. This review is the first to gather together published studies conducted both in vitro and in numerous vertebrate species to demonstrate that these compounds target aging pathways at the cellular level and provide benefits in multiple aging-associated conditions in relevant animal models and in humans. The dogfish aminosterols should be recognized as potential anti-aging drugs.

Extracellular vesicles (EVs) offer valuable diagnostic and prognostic insights for cardiovascular (CV) diseases, but the influence of age-related chronic inflammation ("inflammaging") and sex differences on EV profiles linked to CV risk remains unclear. This study aimed to use EV profiling to predict age and stratify patients by CV risk. We developed an EVaging index by analyzing surface antigen profiles of serum EVs from 625 participants, aged 20 to 94 years, across varying CV risk groups. The EVaging index was associated with age in healthy individuals and distinguished CV risk profiles in patients, correlating with CV outcomes and likelihood of fatal CV events according to the European Society of Cardiology (ESC) SCORE, and reflecting age-associated comorbidities. While changes in disease-related EV fingerprint adds complexity in CV patients, EV profiling may help assess biological aging and CV risk, emphasizing EVs' roles in inflammaging.

The magnitude of benefit of Mediterranean diet in cancer prevention and mortality in older adults is still unclear, therefore we conducted a systematic review and meta-analysis. Outcomes considered were cancer incidence and cancer mortality. In studies evaluating cancer incidence as a time-to-event endpoint and adherence as quantiles, HR was 0.885 (95% CI 0.773-1.013, I² = 44%). Including ORs, exploratory pooled effect size was 0.876 (0.794-0.966, I² = 34%), consistently with results of studies evaluating ORs for adherence as one-point increase (OR 0.744, 0.570-0.972, I² = 90%). No clear benefit was observed on cancer mortality, with pooled HR of 0.935 (0.800-1.093, I² = 0%). Significant differences were observed for ORs according to cancer type but not between medium and high adherence for both outcomes. Certainty of evidence was low. Our findings suggest that MD could play a protective role in cancer incidence in advanced age, but no clear effect on cancer mortality was observed.

There is a growing need to better characterise senescent cells in the CNS and retina. The recently published SenMayo gene panel was developed to identify transcriptomic signatures of senescence across multiple organ systems, but the retina was not included. While other approaches have identified senescent signatures in the retina, these have largely focused on experimental models in young animals. We therefore conducted a detailed single-cell RNA-seq analysis to identify senescent cell populations in the retina of different aged mice and compared these with five comprehensive human and mouse retina and brain transcriptome datasets. Transcriptomic signatures of senescence were most apparent in mouse and human retinal glial cells, with IL4, 13 and 10 and the AP1 pathway being the most prominent markers involved. Similar levels of transcriptional senescence were observed in the retinal glia of young and old mice, whereas the human retina showed significantly increased enrichment scores with advancing age.

Recent advances in single-cell technologies have facilitated studies on age-related alterations in the immune system. However, previous studies have often employed different marker genes to annotate immune cell populations, making it challenging to compare results. In this study, we combined seven single-cell transcriptomic datasets, comprising more than a million cells from one hundred and three donors, to create a unified atlas of human peripheral blood mononuclear cells (PBMC) from both young and old individuals. Using a consistent set of marker genes for immune cell annotation, we standardized the classification of immune cells and assessed their prevalence in both age groups. The integrated dataset revealed several consistent trends related to aging, including a decline in CD8⁺ naive T cells and MAIT cells and an expansion of non-classical monocyte compartments. However, we observed significant variability in other cell types. Our analysis of the long non-coding RNA MALAT1^hi T cell population, previously implicated in age-related T cell exhaustion, showed that this population is highly heterogeneous with a mixture of naïve-like and memory-like cells. Despite substantial variation among the datasets when comparing gene expression between age groups, we identified a high-confidence signature of CD8⁺ naive T cell aging marked by an increased expression of pro-inflammatory genes. In conclusion, our study emphasizes the importance of standardizing existing single-cell datasets to enable the comprehensive examination of age-related cellular changes across multiple datasets.

This study investigates why individuals with multimorbidity-two or more chronic conditions-are more prone to adverse outcomes after surgery. In our cohort, ninety-eight of 144 participants had multimorbidity. The myocardial transcriptome and metabolites involved in energy production were measured in 53 and 57 sequential participants, respectively. Untargeted analysis of the metabolome in blood and myocardium was performed in 30 sequential participants. Mitochondrial respiration in circulating mononuclear cells was measured in 70 participants. Results highlighted four main biological processes associated with multimorbidity: DNA damage with epigenetic changes, mitochondrial energy disruption, cellular aging (senescence) and innate immune response. Histone 2B, its ubiquitination enzymes and AKT3 were upregulated in the multimorbid group. Plasma senescence-associated proteins (IL-1β, GM-CSF) increased with more comorbidities. DNA damage and nucleolar instability were specifically apparent in multimorbid myocardium. We conclude that multimorbidity in cardiovascular patients accelerates biological aging, making them more vulnerable to metabolic stress.