Aging & Longevity

Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a...

The mechanisms underlying the impact of probiotic supplementation on health remain largely elusive. While previous studies primarily focus on the discovery of novel bioactive bacteria and alterations in the microbiome environment to explain potential probiotic effects, our research delves into the role of living Lactiplantibacillus (formerly known as Lactobacillus) and their conditioned media, highlighting that only the former, not dead bacteria, enhance the healthspan of Caenorhabditis elegans...

Impaired muscle mitochondrial oxidative capacity is associated with future cognitive impairment, and higher levels of PET and blood biomarkers of Alzheimer's disease and neurodegeneration. Here, we examine its associations with up to over a decade-long changes in brain atrophy and microstructure. Higher in vivo skeletal muscle oxidative capacity via MR spectroscopy (post-exercise recovery rate, k(PCr)) is associated with less ventricular enlargement and brain aging progression, and less atrophy...

Oxidative modifications can disrupt protein folds and functions, and are strongly associated with human aging and diseases. Conventional oxidation pathways typically involve the free diffusion of reactive oxygen species (ROS), which primarily attack the protein surface. Yet, it remains unclear whether and how internal protein folds capable of trapping oxygen (O(2)) contribute to oxidative damage. Here, we report a hidden pathway of protein damage, which we refer to as O(2)-confined...

Aging is associated with increased tumor metastasis and poor prognosis. However, how an aging immune system contributes to the process is unclear. Here, single-cell RNA sequencing reveals that in male mice, aging shifts the lung immune microenvironment towards a premetastatic niche, characterized by an increased proportion of IL-17-expressing γδT (γδ17) and neutrophils. Mechanistically, age-dependent downregulation of the immune trafficking receptor S1pr1 drives the expansion of γδ17. Compared...

Accumulating evidence indicates that cellular senescence is closely associated with osteoarthritis. However, there is limited research on the mechanisms underlying fibroblast-like synoviocyte senescence and its impact on osteoarthritis progression. Here, we elucidate a positive correlation between fibroblast-like synoviocyte senescence and osteoarthritis progression and reveal that GATD3A deficiency induces fibroblast-like synoviocyte senescence. Mechanistically, GATD3A deficiency enhances the...

The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice. During development, AnkG is also expressed at comparable levels in oligodendrocytes and facilitates the efficient assembly of paranodal junctions. However, the physiological roles of glial AnkG in the mature nervous system, and its...

CONCLUSION: This study highlights the significant impact of thyroid dysfunction on frailty in older adults. Lower fT3 levels and the fT3/fT4 ratio emerged as key indicators of increased frailty, particularly on the SOF and EFS scales. Subgroup analysis further emphasized the importance of age-specific assessments, with a lower fT3/fT4 ratio being a critical indicator of frailty in individuals aged ≥ 80 years, while lower TSH levels were significant in those aged < 80 years. Abnormal TSH levels...

A decline in upper limb strength is common with normal aging. However, whether age-related strength decline is paralleled by reduced excitability of descending motor pathways is unclear. The reticulospinal tract is a key subcortical pathway involved in gross motor output and exhibits increased excitability following resistance training. Here, we sought to determine age-related effects on strength and reticulospinal excitability in flexors and extensors of the upper limb in humans. In 15 younger...

This study employed multivariate analysis to investigate the effects of a 14-week multicomponent training program on sedentary adults and older populations, focusing on improvements in physical fitness, health markers, and anthropometric measures. The data included 376 participants aged 30 to 84 years who had been inactive for at least 3 months. Results showed that participants aged 71 and above had lower systolic blood pressure, height, body mass, elbow flexion and extension, sitting and...

Frailty is one of the most concerning aspects of global population aging, and early identification is crucial to prevent or reverse its progression. Simple, universal, and efficient frailty assessment technologies are essential for the timely detection of frailty in older patients. Various multi-dimensional assessment instruments have been developed to quantify frailty phenotypes; we review the literature on wearable sensor technologies leveraged for older person frailty assessment. This review...

Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the gene transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing. We have...

CONCLUSIONS: Excessive increase in FI was positively associated with an increased risk for all-cause mortality. Approaches to reducing FI may be of great significance in improving the health of older Chinese individuals.

CONCLUSIONS: This fall prevention programme with a single home visit was found to be effective and cost effective. Health policies should establish such a model as a reimbursed standard care to assist in combatting the increasing burden of falls on individuals and societies.

Structural inequality, the uneven distribution of resources and opportunities, influences health outcomes. However, the biological embedding of structural inequality in aging and dementia, especially among underrepresented populations, is unclear. We examined the association between structural inequality (country-level and state-level Gini indices) and brain volume and connectivity in 2,135 healthy controls, and individuals with Alzheimer's disease and frontotemporal lobe degeneration from Latin...

We have previously presented a multidimensional Aging Society Index, a weighted summation of five domains central to successful adaptation to societal aging: well-being, productivity and engagement, equity, cohesion and security, as a tool to assess countries' adaptation to demographic transformation. As the index was based on data from developed countries and some of the individual metrics or weightings may not be well suited for application to low- and middle-income countries, we here present...

The emerging field of senolytics is centered on eliminating senescent cells to block their contribution to the progression of age-related diseases, including cancer, and to facilitate healthy aging. Enhancing the selectivity of senolytic treatments toward senescent cells stands to reduce the adverse effects associated with existing senolytic interventions. Taking advantage of lipofuscin accumulation in senescent cells, we describe here the development of a highly efficient senolytic platform...

Although senescent cells can be eliminated by the immune system, they tend to accumulate with age in various tissues. Here we show that senescent cells can evade immune clearance by natural killer (NK) cells by upregulating the expression of the disialylated ganglioside GD3 at their surface. The increased level of GD3 expression on senescent cells that naturally occurs upon aging in liver, lung, kidney or bones leads to a strong suppression of NK-cell-mediated immunosurveillance. In mice, we...

Significant links between aging and DNA methylation are emerging from recent studies. On the one hand, DNA methylation undergoes changes with age, a process termed as epigenetic drift. On the other hand, DNA methylation serves as a readily accessible and accurate biomarker for aging. A key missing piece of information, however, is the molecular mechanisms underlying these processes and how they are related, if any. Addressing the limitations of previous research due to the limited number of...

Aging is accompanied by multiple molecular changes that contribute to aging associated pathologies, such as accumulation of cellular damage and mitochondrial dysfunction. Tissue metabolism can also change with age, in part, because mitochondria are central to cellular metabolism. Moreover, the cofactor NAD^(+), which is reported to decline across multiple tissues during aging, plays a central role in metabolic pathways such as glycolysis, the tricarboxylic acid cycle, and the oxidative synthesis...