Aging & Longevity

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Drugs that eliminate senescent cells, senolytics, can be powerful when combined with prosenescence cancer therapies. Using a CRISPR/Cas9-based genetic screen, we identify here SLC25A23 as a vulnerability of senescent cancer cells. Suppressing SLC25A23 disrupts cellular calcium homeostasis, impairs oxidative phosphorylation, and interferes with redox signaling, leading to death of senescent cells. These effects can be replicated by salinomycin, a cation ionophore antibiotic. Salinomycin prompts a...

Biological aging clocks produce age estimates that can track with age-related health outcomes. This study aimed to benchmark machine learning algorithms, including regularized regression, kernel-based methods, and ensembles, for developing metabolomic aging clocks from nuclear magnetic resonance spectroscopy data. The UK Biobank data, including 168 plasma metabolites from up to N = 225,212 middle-aged and older adults (mean age, 56.97 years), were used to train and internally validate 17...

CONCLUSION: Multimorbidity is strongly associated with accelerated kidney function decline in older age. Individuals with cardiometabolic multimorbidity exhibit a particularly increased risk. Increased monitoring and timely interventions may preserve kidney function and reduce cardiovascular risks in individuals presenting with conditions that are characteristic of high-risk multimorbidity patterns.

Calorie restriction (CR) and physical exercise (EX) are well-established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long-term follow-up. This study compared BioAge biomarkers in 41 middle-aged and older adult long-term CR...

Aging is marked by a decline in tissue regeneration, posing significant challenges to an increasingly older population. Here, we investigate age-related impairments in calvarial bone healing and introduce a novel two-part rejuvenation strategy to restore youthful repair. We demonstrate that aging negatively impacts the calvarial bone structure and its osteogenic tissues, diminishing osteoprogenitor number and function and severely impairing bone formation. Notably, increasing osteogenic cell...

Does precision in auditory perception predict precision in subsequent memory (i.e., mnemonic discrimination) in aging? This study examined if the mismatch negativity (MMN), an electrophysiological marker of change detection and encoding, relates to age differences in mnemonic discrimination. The MMN was recorded in 92 adults (18-86 years, 47 females) in a passive oddball paradigm using tone sequences. Participants then completed a surprise recognition test for presented sequences (i.e., old...

Reduced somatostatin (SST) and SST-expressing GABAergic neurons are well-replicated findings in Alzheimer's disease (AD) and are associated with cognitive deficits. SST cells inhibit pyramidal cell dendrites through α5-GABA-A receptors (α5-GABAA-R). α5-GABAAR positive allosteric modulation (α5-PAM) has procognitive and neurotrophic effects in stress and aging models. We tested whether α5-PAM (GL-II-73) could prevent cognitive deficits and neuronal spine loss in early stages, and reverse them in...

Throughout adulthood and ageing our brains undergo structural loss in an average pattern resembling faster atrophy in Alzheimer's disease (AD). Using a longitudinal adult lifespan sample (aged 30-89; 2-7 timepoints) and four polygenic scores for AD, we show that change in AD-sensitive brain features correlates with genetic AD-risk and memory decline in healthy adults. We first show genetic risk links with more brain loss than expected for age in early Braak regions, and find this extends beyond...

CONCLUSION: Chronic pain is significantly associated with an elevated risk of cognitive frailty among middle-aged and elderly individuals. These findings highlight the importance of managing chronic pain to mitigate the risk of cognitive frailty, thereby potentially enhancing the quality of life for the aging population and alleviating the economic burden on families and society.

The oxidative stress-induced premature senescence of trabecular meshwork (TM) represents a pivotal risk factor for the development of glucocorticoid-induced glaucoma (GIG). This study aimed to elucidate the pathogenesis of TM senescence in GIG. MethodsIntraocular pressure (IOP), transmission electron microscopy and senescence-associated protein expression in TM were evaluated in GIG mice. Protein expression of phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and monoamine oxidase A...

The mitochondrial genome (mtDNA) is an important source of inherited extranuclear variation. Clonal increases in mtDNA mutation heteroplasmy have been implicated in aging and disease, although the impact of this shift on cell function is challenging to assess. Reprogramming to pluripotency affects mtDNA mutation heteroplasmy. We reprogrammed three human fibroblast lines with known heteroplasmy for deleterious mtDNA point or deletion mutations. Quantification of mutation heteroplasmy in the...

INTRODUCTION: Subjective visual impairment (VI) is related to cognition in cognitively unimpaired (CU) older adults, mild cognitive impairment (MCI) patients, and Alzheimer's disease (AD) patients. The utility of subjective VI as an indicator for domain-specific cognitive impairment is unknown.

CONCLUSION: The incorporation of AI methodologies such as GNNs and MLPs into clinical settings holds promise for enhancing the diagnosis and management of Alzheimer's disease and mild cognitive impairment. By deploying these advanced computational techniques, clinicians could see a reduction in diagnostic errors, facilitating earlier, more precise interventions, and likely to lead to significantly improved outcomes for patients.

CONCLUSION: An elevated CMI is linked to increased risk for biological aging. This relationship may inform more effective prevention and treatment strategies for biological aging in the future. CMI be integrated into routine health screenings or aging assessments by healthcare professionals.

Microbial infectivity increases with rising environmental temperature, heightening the risk of infection to host organisms. The host's basal immunity is activated accordingly to mitigate upcoming pathogenic threats; still, how animals sense temperature elevation to adjust their preventive immune response remains elusive. This study reports that high temperature enhances innate immunity differently from pathogen infection. Unlike pathogen invasion requiring the mitochondrial unfolded protein...

CONCLUSIONS AND IMPLICATIONS: Long-term care needs assessment is a complex but necessary task to be performed by long-term care systems. Countries embarking in the design and redesign of their systems can use the existing instruments, frameworks, and the experience from other countries to better adapt this process to their own needs and contexts.

The critical role of some RAB family members in oocyte meiosis has been extensively studied, but their role in oocyte aging remains poorly understood. Here, we report that the vesicle trafficking regulator, RAB9 GTPase, is essential for oocyte meiosis and aging in humans and mice. RAB9 was mainly located at the meiotic spindle periphery and cortex during oocyte meiosis. In humans and mice, we found that the RAB9 protein level were significantly increased in old oocytes. Age-related accumulation...

The immune system is intricately interconnected with all other bodily systems. As individuals age, the immune system undergoes changes known as immunosenescence, increasing susceptibility to disease, and contributing significantly to the morbidity and mortality observed in older populations. Immunosenescence drives systemic aging and therefore represents a key therapeutic target to extend healthy aging. In recent years, the extensive application of omics technologies has broadened our...