Aging & Longevity

Age-related macular degeneration (AMD) is a leading cause of blindness in elderly populations, yet the molecular events that initiate the early retinal defects that lead to visual function deficits remain poorly understood. The studies here explored a role for the stress response protein Regulated in Development and DNA damage response 1 (REDD1) in the development of retinal pathology by using the oxidant stressor sodium iodate (NaIO(3)) to model dry AMD in mice. REDD1 protein abundance was...

Alterations in the nuclear envelope are linked to a variety of rare diseases termed laminopathies. A single amino acid substitution at position 12 (A12T) of the human nuclear envelope protein BAF (Barrier to Autointegration Factor) causes Néstor-Guillermo Progeria Syndrome (NGPS). This premature ageing condition leads to growth retardation and severe skeletal defects, but the underlying mechanisms are unknown. Here, we have generated a novel in vivo model for NGPS by modifying the baf-1 locus in...

Mitophagy neutralizes mitochondrial damage, thereby preventing cellular dysfunction and apoptosis. Defects in mitophagy have been strongly implicated in age-related neurodegenerative disorders such as Parkinson's and Alzheimer's disease. While mitophagy decreases throughout the lifespan of short-lived model organisms, it remains unknown whether such a decline occurs in the aging mammalian brain-a question of fundamental importance for understanding cell type- and region-specific susceptibility...

Although most drugs currently approved are meant to treat specific diseases or symptoms, it has been hypothesized that some might bear a beneficial effect on lifespan in healthy older individuals, outside of their specific disease indication. Such drugs include, among others, metformin, SGLT2 inhibitors and rapamycin. Since 2006, the UK biobank has recorded prescription medication and mortality data for over 500'000 participants, aged between 40 and 70 years old. In this work, we examined the...

Recently, it is discovered PF4 is a cognitive enhancer that improved the cognitive abilities of younger mice and gave older animals their middle-aged acuity back. PF4 works by reducing inflammation during the aging process. As we all known, aging is undoubtedly the main risk factor of neurodegenerative diseases. Furthermore, inflammation has been extensively investigated and attracted even more interest. Therefore, the aim of the proposal is to highlight the worth of PF4 in inflammaging of...

Tree growth and longevity trade-offs fundamentally shape the terrestrial carbon balance. Yet, we lack a unified understanding of how such trade-offs vary across the world's forests. By mapping life history traits for a wide range of species across the Americas, we reveal considerable variation in life expectancies from 10 centimeters in diameter (ranging from 1.3 to 3195 years) and show that the pace of life for trees can be accurately classified into four demographic functional types. We found...

Objectives: Death anxiety is feelings of worry and fear regarding death. This study explored the effect of number of chronic conditions on death anxiety in older adults and the moderating effect of age. Methods: This study used the fifth, sixth, seventh, and eighth waves of longitudinal data (2012-2021) collected in Anhui, China (5014 person-year observations). A mixed linear model was used to examine the effect of number of chronic conditions on death anxiety and the moderating effect of age....

Chronic sterile inflammation contributes to aging-associated pathologies/malignancies like cancer and autoimmune disorders. In their recent Nature article, Widjaja et al. established the pro-inflammatory, pro-fibrotic cytokine 11 (IL11) as a regulatory driver/hub of aging-associated inflammation (inflammaging) in mice. Genetic and pharmacological IL11 blockade reduces inflammaging, improving healthspan, lifespan, and longevity in male and female mice, highlighting IL11 as a new inflammatory...

CONCLUSION: The prevalence of frailty in gastric cancer is common and has a significant adverse effect on GC patients' outcomes. Our findings highlight the importance of routine frailty assessment in GC patients, which may provide prognostic outcomes.

Dietary restriction (DR) extends lifespan in various species, but its effect at different ages, especially when started later, is unclear. This study used Caenorhabditis elegans to explore the impact of DR at different ages. Worms were divided into control and DR groups, with daily survival monitored. To confirm the occurrence of DR, the expression of DR-sensitive genes namely acdh-1, pyk-1, pck-2 and cts-1 were determined using RT-qPCR. Liquid chromatography mass spectrometry (LC-MS) was...

Chronic pain remains a significant medical challenge with complex underlying mechanisms, and an urgent need for new treatments. Our research built and utilized the iPain single-cell atlas to study chronic pain progression in dorsal root and trigeminal ganglia. We discovered that senescence of a small subset of pain-sensing neurons may be a driver of chronic pain. This mechanism was observed in animal models after nerve injury and in human patients diagnosed with chronic pain or diabetic painful...

While the activities of certain proteases promote proteostasis and prevent neurodegeneration-associated phenotypes, the protease cathepsin B (CTSB) enhances proteotoxicity in Alzheimer's disease (AD) model mice, and its levels are elevated in brains of AD patients. How CTSB exacerbates the toxicity of the AD-causing Amyloid β (Aβ) peptide is controversial. Using an activity-based probe, aging-altering interventions and the nematode C. elegans, we discovered that the CTSB CPR-6 promotes Aβ...

Ageing is a complex biological process in which a gradual decline in physiological fitness increases susceptibility to diseases such as neurodegenerative disorders and cancer. Cellular senescence, a state of irreversible cell-growth arrest accompanied by functional deterioration, has emerged as a pivotal driver of ageing. In this Review, we discuss how heterochromatin loss, telomere attrition and DNA damage contribute to cellular senescence, ageing and age-related diseases by eliciting genome...

With aging, the body's ability to maintain regular functions declines, increasing susceptibility to age-related diseases. Therapeutic interventions targeting the underlying biological changes of aging hold promise for preventing or delaying multiple age-related diseases. Metformin, a drug commonly used for diabetes treatment, has emerged as a potential gerotherapeutic agent due to its established safety record and preclinical and clinical data on its anti-aging effects. Glycosylation, one of the...

The intrinsic brain functional network organization continuously changes with aging. By integrating spatial and temporal information, the process of how brain networks temporally reconfigure and remain well-organized spatial structure largely reflects the brain function, thereby holds the potential to capture its age-related declines. In this study, we examined the spatiotemporal brain dynamics from resting-state functional Magnetic Resonance Imaging (fMRI) data of healthy young and older adults...

CONCLUSION: The developed SSWTRT reflects the assessment results of neuropsychological tests in cognitive deterioration and was able to detect early cognitive deficits. This test not only relates to visual perception but is likely to have an association with verbal fluency and memory ability, which are frontal lobe functions.

We aimed to examine the white matter changes associated with lexical production difficulties, beginning in midlife with increased naming latencies. To delay lexical production decline, middle-aged adults may rely on domain-general and language-specific compensatory mechanisms proposed by the LARA model (Lexical Access and Retrieval in Aging). However, the white matter changes supporting these mechanisms remains largely unknown. Using data from the CAMCAN cohort, we employed an unsupervised and...

The prevalence of sleep disorders has been reported from 1.6% to 56.0%, worldwide. Sleep deprivation causes cardiovascular diseases (CVDs) including atherosclerosis, vascular aging, hypertension, heart dysfunction, reduced heart rate variability, and cardiac arrhythmia. Reduced tissue oxygen causes various CVDs by activating pro-inflammatory factors and increasing oxidative stress. Sleep disorders are more important and prevalent in older people and cause more severe cardiovascular...

Ageing impairs the ability of neural stem cells (NSCs) to transition from quiescence to proliferation in the adult mammalian brain. Functional decline of NSCs results in the decreased production of new neurons and defective regeneration following injury during ageing^(1-4). Several genetic interventions have been found to ameliorate old brain function^(5-8), but systematic functional testing of genes in old NSCs-and more generally in old cells-has not been done. Here we develop in vitro and in...

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