Aging & Longevity

The transcription factors FOXO4 and p53 regulate aging, and their deregulation has been linked to several diseases, including cancer. Under stress conditions, cellular senescence is promoted by p53 sequestration and senescence-associated protein p21 transcriptional upregulation induced by interactions between the FOXO4 Forkhead DNA-binding domain and the p53 transactivation domain. However, the molecular details of these interactions remain unclear. Here, we report that these interactions...

Pancreatic ductal adenocarcinoma (PDAC) is an age-associated malignancy closely linked to the extracellular matrix (ECM). However, the impact of age-related ECM changes in the normal pancreas on PDAC progression remains unclear. Here, we find that increased linear ECM alignment in normal pancreatic tissues from aged PDAC patients is associated with PDAC progression and worse outcomes. Furthermore, serum methylmalonic acid (MMA) levels are elevated in aged PDAC patients and associated with...

Polyamines are abundant and evolutionarily conserved metabolites that are essential for life. Dietary polyamine supplementation extends life-span and health-span. Dysregulation of polyamine homeostasis is linked to Parkinson's disease and cancer, driving interest in therapeutically targeting this pathway. However, measuring cellular polyamine levels, which vary across cell types and states, remains challenging. We introduce a genetically encoded polyamine reporter for real-time measurement of...

Breakdown of calcium network is closely associated with cellular aging. Previously, we found that cytosolic calcium (CytoCa^(2+)) levels were elevated while mitochondrial calcium (MitoCa^(2+)) levels were decreased and associated with metabolic shift in aged intestinal stem cells (ISCs) of Drosophila. How MitoCa^(2+) was decoupled from the intracellular calcium network and whether the reduction of MitoCa^(2+) drives ISC aging, however, remains unresolved. Here, we show that genetically restoring...

Mitochondria rapidly accumulate mutations throughout a lifetime, potentially acting as a molecular clock for aging and disease. We profiled mitochondrial RNA across 47 human tissues from 838 individuals, revealing rapid development of clonal mosaicism with two distinct tissue-specific aging signatures. Tissues with constant cellular turnover such as the gastrointestinal tract or skin exhibit accelerated accumulation of sporadic mutations and clonal expansions, implicating increased...

While memory regulation is predominantly understood as autonomous to neurons, factors outside the brain can also affect neuronal function. In Caenorhabditis elegans, the insulin/IGF-1-like signaling (IIS) pathway regulates longevity, metabolism and memory: long-lived daf-2 insulin/IGF-1 receptor mutants more than double memory duration after a single training session, and it was assumed that memory regulation was strictly neuronal. However, here we show that degradation of DAF-2 in the...

Geroprotectors are compounds that target the underlying mechanisms of ageing to delay the onset of age-related diseases and extend both lifespan and health span. As ageing is driven by the accumulation of cellular damage, DNA instability, epigenetic changes, mitochondrial dysfunction, and chronic inflammation, the concept of geroprotection focuses on compounds that can mitigate these processes. Oleuropein (OLE) and its derivative hydroxytyrosol (HT), both phenolic molecules derived from Olea...

CONCLUSION: The higher the levels of emotional, psychological, and spiritual well-being, the higher the life satisfaction of older persons 60 years and older. However, the higher the level of self-reported physical well-being, the less likely to experience high life satisfaction. Emphasis should be on high physical well-being, promoting high life satisfaction and healthy ageing among older persons in Ghana.

Metformin, a medication primarily used to treat diabetes, has gained attentions for its potential antiaging properties. Although the metabolic and cellular pathways behind its longevity effects have been widely studied, few studies have explored the epigenetic regulatory effects of metformin, which are a crucial factor in aging processes. In this study, we examined the antiaging effects of metformin using the Brachionus rotifer as a model, focusing on the regulation of mRNA N6-methyladenosine...

We conducted a randomized, placebo-controlled trial to assess the safety and biological age (BA) effects of various therapeutic plasma exchange (TPE) regimens in healthy adults over 50. Participants received bi-weekly TPE with or without intravenous immunoglobulin (IVIG), monthly TPE, or placebo. Randomization was based on entry date, and treatments were blinded to maintain objectivity. Primary objectives were to assess long-term TPE safety and changes in biological clocks. Secondary goals...

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing and is caused by excessive fat deposition in the liver due to non-alcoholic factors. Aging is a major risk factor for the development and progression of MASLD. In this study, we investigated the metabolic effects of tilorone, a synthetic small molecule, in a high-fat diet (HFD) mouse model, with a focus on the liver function and signaling. We demonstrate that tilorone attenuated HFD-induced...

BACKGROUND: Healthy ageing is defined as a process of preserving functional capacity to enable well-being in old age. This concept includes both a physical and a psychological component, which can be positively influenced by spending time in nature and being physically active. Mountainous areas offer diverse opportunities to be physically active in a natural environment. However, little research is available on the psychological effects of mountain environments and mountain sports, particularly...

Preeclampsia (PE) is a hypertensive disorder of pregnancy, among the leading global drivers of maternal morbidity. PE can precipitate neuropsychiatric risk, including for peripartum anxiety, depression, and cognitive problems. To investigate mechanisms underlying psycho-obstetric risk in PE, we examined maternal metabolic, placental, brain, and behavioral changes in our chronic vasopressin (AVP) infusion PE mouse model (C57Bl6/J). Elevated maternal AVP secretion predicts PE in humans, and...

Despite the growing interest in developing anti-aging drugs, high costs and low success rates of traditional drug discovery methods pose significant challenges. Aging is a complex biological process associated with numerous diseases, making the identification of compounds that can modulate aging mechanisms critically important. Accelerating the discovery of potential anti-aging compounds is essential to overcome these barriers and enhance lifespan and healthspan. Here, we present ElixirSeeker, a...

Multi-organ biological aging clocks across different organ systems have been shown to predict human disease and mortality. Here, we extend this multi-organ framework to plasma metabolomics, developing five organ-specific metabolome-based biological age gaps (MetBAGs) using 107 plasma non-derivatized metabolites from 274,247 UK Biobank participants. Our age prediction models achieve a mean absolute error of approximately 6 years (0.25

Profiling post-translational modifications face challenges with low-input samples. We developed Iseq-Kac (internal standard-assisted enrichment-free approach for high-throughput quantitative analysis of lysine acetylation) to profile the acetylome in as few as 10³-10⁴ cells. By using a hyperacetylated internal standard, Iseq-Kac can be used in mass spectrometry (MS) to enhance MS1 signals and facilitate MS2 fragmentation of acetylated peptides. Using Iseq-Kac, we quantified 675-1,471 acetylated...

As societies age, policy makers need tools to understand how demographic aging will affect population health and to develop programs to increase healthspan. The current metrics used for policy do not distinguish differences caused by early-life factors, like prenatal care and nutrition, from those caused by ongoing changes in people's bodies that are due to aging and that may be modifiable. Here we introduce an adapted Pace of Aging method designed to quantify differences between individuals and...

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CONCLUSION: The findings of this study indicated that social isolation can predict COVID-19 anxiety in older adults. It is expected that policymakers and family members of older adults will take steps to enhance community-oriented approaches, such as group meetings and face-to-face visits, while adhering to the relevant health protocols.

Aging is associated with cognitive decline, and currently, there are no approved medications that can prevent these impairments. Recently, cannabinoids derived from Cannabis sativa have emerged as promising therapeutic compounds with neuroprotective, anti-inflammatory, and cognitive-enhancing properties. Despite their benefits, further research is needed to fully understand their efficacy across various conditions. This study investigates the effects of cannabidiol (CBD) on memory impairment and...