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This review delves into the intricate relationship between serotonin signaling, mitophagy and mitochondrial dysfunction in Alzheimer's disease (AD), with a focus on the mechanistic pathways that link these processes and their potential therapeutic implications. A neurodegenerative condition called Alzheimer's disease is marked by cognitive deterioration. It is increasingly recognized as being influenced by impaired mitochondrial function and mitophagy, the selective degradation of damaged...

Alzheimer's disease (AD), the most common cause of dementia, is characterized by amyloid-β deposition, tau hyperphosphorylation, neuroinflammation, and progressive neuronal loss, with no curative therapy currently available. Dental pulp stem cells (DPSCs) derived from third molars represent an ethically accessible, minimally invasive, neural crest-derived mesenchymal stem cell source with self-renewal and multi-lineage differentiation potential. Preclinical evidence suggests that DPSCs exert...

Though interest has grown significantly over the past decades in interventions that may slow the aging process, most evidence for these interventions still comes from experiments in non-human animals. These studies may suffer from design, quality and reporting issues. The quality and reporting of preclinical studies have not yet been studied systematically in anti-aging research. Here we analyzed the DrugAge database, assessing reporting study quality, bias and effect sizes across 667 anti-aging...

Multivitamin and mineral (MVM) supplements are among the most widely used dietary supplements globally, however, their role in promoting healthspan and longevity remains unclear. This review evaluated comprehensive findings from meta-analyses to clarify their health effects. A rapid review of MEDLINE and EMBASE identified 19 eligible meta-analyses published from 2000 to 2025, encompassing 5,535,426 participants, including over 333,943 pregnancies and 904,947 children exposed to maternal MVM...

The 5-HT7 receptor subtype is expressed throughout the brain, including the cortex and hippocampus, and it has been implicated in the molecular mechanisms underlying memory and affective behaviors. Although aging also affects memory and behavior, how 5-HT7 receptor interacts with age-related changes of these phenotypes has not been fully elucidated. To further understand the role of 5-HT7 receptor on memory and affective behaviors across the lifespan, we assessed age-related changes in locomotor...

Obesity poses a significant public health challenge among middle-aged women, driven by physiological changes associated with aging and menopause. This parallel-group, assessor-blinded, four-arm randomized controlled trial investigated the effects of 12-week 8-hour flexible time-restricted eating (flexTRE) and aerobic exercise (EX), alone or in combination (flexTRE+EX), on body composition and metabolic health in a free-living setting. Participant enrolment began on September 1^(st) 2023 and data...

Intestinal P-glycoprotein (P-gp/ABCB1) is a key barrier limiting xenobiotic absorption, yet its functional decline with aging is poorly understood. Here, we show that gut microbiota dysbiosis contributes to age-associated P-gp deficiency. Integrated multi-omics analyses of human cohorts and murine models identify Odoribacter splanchnicus (O. splanchnicus) as a key commensal species whose depletion impairs intestinal P-gp function. Mechanistically, O. splanchnicus encodes GDP-mannose 4,...

Survivors of childhood cancer are prone to neurocognitive impairment and premature aging, raising concerns about early onset dementia. In this cross-sectional study, 1413 survivors of childhood cancer complete a neuropsychological battery. Mean leukocyte telomere length residual (mLTL) and epigenetic age acceleration (EAA) from five different epigenetic clocks, are derived from linear regression of mLTL or epigenetic age on chronological age. Among survivors treated with CNS-directed therapy,...

Synapse dysfunction is tightly linked to cognitive changes during aging. Emerging evidence suggests that microglia and the extracellular matrix (ECM) can potently regulate synapse integrity and plasticity. Yet the brain ECM, and its relationship with microglia, synapses, and cognition during aging remains virtually unexplored. In this study we combine ECM-optimized proteomic workflows with histological analyses in aging mice and discover regional differences in ECM composition and aging-induced...

As Earth's magnetic field weakens, space radiation begins to pose a significant threat to the health of not only space travelers, but the world's population. Space radiation, comprising high-energy and high-charge ions, creates distinct clusters of DNA damage and dense macromolecular damage that result in the accumulation of senescent cells (SnCs) known to play a critical role in promoting multimorbidity. Here, we demonstrate that human fibroblasts exposed to different forms of space radiation...

Many cellular functions rely on multiprotein complexes and their stoichiometric assembly. Reducing the levels of individual complex components can perturb this process and induce corrective stress responses. In addition to local outcomes, cellular stress in one tissue can induce long-distance responses in other tissues. Here, we used muscle-targeted RNAi to examine the systemic stress responses induced by muscle-specific genetic perturbation of four distinct multiprotein complexes: the...

Plasma biomarkers of Alzheimer's disease and related dementias (ADRD) are associated with the risk of dementia. However, the extent to which they could reflect cognitive ageing, and whether this is consistent across factors known to influence biomarkers (e.g. sex and chronic kidney disease) and in different populations, is unknown. Data were from a diverse community-dwelling cohort of older individuals without dementia in Australia (n = 11,930) and the US (n = 1,181). Global cognition, verbal...

The cerebellum, essential for motor coordination and increasingly recognized for its role in cognition, is typically considered more resilient to aging and largely spared from hallmark Alzheimer's disease (AD) pathology. However, transcriptomic analyses across fifteen mouse brain regions revealed that the cerebellum undergoes some of the earliest and most pronounced age-related changes. To investigate cerebellar aging, we applied single-nucleus RNA sequencing (RNA-seq), microglial bulk RNA-seq,...

The end replication problem refers to incomplete replication of parental DNA at telomeres, a process whose molecular depiction is hampered by the complex nature of telomere ends. Here, we recapitulate this process using a synthetic de novo telomere in Saccharomyces cerevisiae and delineate distinct molecular fates of telomere ends in vivo. We show that the lagging-strand telomeres carry a ∼10 nt 3' overhang, while the leading-strand telomeres have a Yku-protected blunt end, a feature that is...

The cerebellum, essential for motor coordination and increasingly recognized for its role in cognition, is typically considered more resilient to aging and largely spared from hallmark Alzheimer's disease (AD) pathology. However, transcriptomic analyses across fifteen mouse brain regions revealed that the cerebellum undergoes some of the earliest and most pronounced age-related changes. To investigate cerebellar aging, we applied single-nucleus RNA sequencing (RNA-seq), microglial bulk RNA-seq,...

Aging or injury to the joints can lead to cartilage degeneration and osteoarthritis (OA), for which there are limited effective treatments. We found that expression of 15-hydroxy prostaglandin dehydrogenase (15-PGDH) is increased in the articular cartilage of aged or injured mice. Both systemic and local inhibition of 15-PGDH with a small molecule inhibitor (PGDHi) led to regeneration of articular cartilage and reduction in OA-associated pain. Using single cell RNA-sequencing and multiplexed...

CONCLUSIONS: The study highlighted the social and financial obstacles hindering the use of ICOPE Monitor and more broadly, the implementation of frailty screening by primary care practitioners.

CONCLUSION: Prolonged MFB-ICSS treatment mitigates cognitive deficits, modulates circulating levels of miRNA-495 and miR-146a, restores hippocampal NRF2 levels, and preserves corpus callosum integrity in the SAD rat model by STZ injection. These findings highlight the therapeutic potential of MFB-ICSS as a non-pharmacological intervention in AD. Furthermore, this study confirms NRF2 as a target of miR-495 in the context of AD.

Studies in laboratory organisms typically minimize all environmental and genetic variation other than the intervention of interest. In aging studies, these highly controlled conditions have yielded profound insights into aging. But even within isogenic cohorts of lab animals in controlled environments, we observe substantial variation in lifespan. Here we exploited the climbing behavior of Drosophila to study variation in mortality among isogenic populations in a controlled environment. We show...

Human umbilical cord blood (HUCB) exhibits distinct characteristics compared to adult blood, offering significant potential for medical applications, particularly in antiaging therapies. However, the metabolic profile of HUCB relative to adult blood remains poorly understood. Moreover, the specific metabolites within HUCB that confer antiaging properties have yet to be identified. Here, we conducted an untargeted metabolomic analysis comparing cord plasma and adult plasma. Our results reveal a...