Aging & Longevity

Cellular senescence plays critical roles in aging, regeneration, and disease; yet, the ability to discern its contributions across various cell types to these biological processes remains limited. In this study, we generated an in vivo genetic toolbox consisting of three p16^(Ink4a)-related intersectional genetic systems, enabling pulse-chase tracing (Sn-pTracer), Cre-based tracing and ablation (Sn-cTracer), and gene manipulation combined with tracing (Sn-gTracer) of defined p16^(Ink4a+) cell...

Obesity is one of the most prevalent and increasing metabolic disorders and is considered one of the twelve risk factors for dementia. Numerous studies have demonstrated that obesity induces pathophysiological changes leading to cognitive decline; however, the underlying molecular mechanisms are yet to be fully elucidated. Various biochemical processes, including chronic inflammation, oxidative stress, insulin resistance, dysregulation of lipid metabolism, disruption of the blood-brain barrier,...

CONCLUSION: In summary, the existing evidence from RCTs suggests that traditional Daoyin therapy, such as Taichi, Baduanjin, and Wuqinxi, is a promising strategy that can improve cognitive function and delay the onset of dementia in older adults with MCI by altering structural and neural activities and modulating other factors.

CONCLUSION: Some mortality prediction models showed promising results for use in practice and most studies were of sufficient quality. However, more uniform methodology and validation studies are needed for clinical implementation.

Complex pathways involving the DNA damage response (DDR) contend with cell-intrinsic and -extrinsic sources of DNA damage. DDR mis-regulation results in genome instability that can contribute to aging and diseases including cancer and neurodegeneration. Recent studies have highlighted key roles for several RNA species in the DDR, including short RNAs and RNA/DNA hybrids (R-loops) at DNA break sites, all contributing to efficient DNA repair. RNAs can undergo more than 170 distinct chemical...

Despite aging being one of the strongest risk factors for cancer, little is known about the biological mechanisms that promote tumor initiation. In this issue of Cancer Cell, Yan et al. address this fundamental question in the context of breast cancer and report that midkine is upregulated during the aging process and can promote tumorigenesis.

Aging is a pivotal risk factor for cancer, yet the underlying mechanisms remain poorly defined. Here, we explore age-related changes in the rat mammary gland by single-cell multiomics. Our findings include increased epithelial proliferation, loss of luminal identity, and decreased naive B and T cells with age. We discover a luminal progenitor population unique to old rats with profiles reflecting precancerous changes and identify midkine (Mdk) as a gene upregulated with age and a regulator of...

CONCLUSION: The developed domain-specific IC scores and the composite IC score effectively discriminated age-related declines in IC. Additionally, the composite IC score was longitudinally associated with functional limitations. By creating this comprehensive and reliable tool for tracking IC, we aim to provide valuable insights into the dynamics of ageing and support more effective strategies for promoting health and well-being throughout later life. These scores establish a foundation for...

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...