Aging & Longevity

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Exploring the genomic basis of transcriptional programs has been a long-standing research focus. Here we report a single-cell method, ChAIR, to map chromatin accessibility, chromatin interactions and RNA expression simultaneously. After validating in cultured cells, we applied ChAIR to whole mouse brains and delineated the concerted dynamics of epigenome, three-dimensional (3D) genome and transcriptome during maturation and aging. In particular, gene-centric chromatin interactions and open...

Transposable elements (TEs) are mobile repetitive nucleic acid sequences that have been incorporated into the genome through spontaneous integration, accounting for almost 50% of human DNA. Even though most TEs are no longer mobile today, studies have demonstrated that they have important roles in different biological processes, such as ageing, embryonic development, and cancer. TEs influence these processes through various mechanisms, including active transposition of TEs contributing to...

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Elucidating the regulatory mechanisms of human cardiac aging remains a great challenge. Here, using human heart tissues from 74 individuals ranging from young (≤35 years) to old (≥65 years), we provide an overview of the histological, cellular and molecular alterations underpinning the aging of human hearts. We decoded aging-related gene expression changes at single-cell resolution and identified increased inflammation as the key event, driven by upregulation of ARID5A, an RNA-binding protein....

Theta-gamma transcranial alternating current stimulation (TG tACS) over primary motor cortex (M1) can improve ballistic motor performance in young adults, but the effect on older adults is unknown. This study investigated the effects of TG tACS on motor performance and M1 excitability in 18 young and 18 older adults. High-definition TG tACS (6 Hz theta, 75 Hz gamma) or sham tACS was applied over right M1 for 20 min during a ballistic left-thumb abduction motor training task performed in two...

During aging, microglia - the resident macrophages of the brain - exhibit altered phenotypes and contribute to age-related neuroinflammation. While numerous hallmarks of age-related microglia have been elucidated, the progression from homeostasis to dysfunction during the aging process remains unresolved. To bridge this gap in knowledge, we undertook complementary cellular and molecular analyses of microglia in the mouse hippocampus across the adult lifespan and in the experimental aging model...

Higher cardiorespiratory fitness (CRF) is associated with less deterioration in brain microstructural white matter (WM) integrity in older adults assessed with MRI diffusion tensor imaging (DTI) and brain WM hyperintensities (WMH) volume measured with fluid-attenuated-inversion-recovery (FLAIR) imaging. This study investigated associations of CRF measured with peak oxygen consumption (V̇O(2peak)) with brain WM microstructural integrity and WMH in healthy individuals across the adult lifespan. We...

Biological age (BA), compared to chronological age, offers a more accurate reflection of aging status. In this prospective UK Biobank study, BA acceleration was measured using the Klemera-Doubal method BA (KDM-BA) and Phenotypic age (PhenoAge). Cox models estimated associations of BA acceleration with incident T2D (n = 271,885) and CAD (n = 270,054). Both additive and multiplicative interactions between BA acceleration and polygenic risk score (PRS) were examined. Predictive performance was...

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CONCLUSIONS: Postural imbalance is a common occurrence in a vulnerable older population in Brazil. Importantly, we found that depressive symptomatology was associated with increased odds of having postural imbalance and postural imbalance with falls experienced in the previous 6 months. Notwithstanding our analyses' exploratory nature, these issues should receive greater attention in primary care practice and research.

Aging is a universal biological process that impacts all tissues, leading to functional decline and increased susceptibility to age-related diseases, particularly cardiometabolic disorders. While aging is characterized by hallmarks such as mitochondrial dysfunction, chronic inflammation, and dysregulated metabolism, the molecular mechanisms driving these processes remain incompletely understood, particularly in a tissue-specific context. To address this gap, we conducted a comprehensive...

DNA damage repair is a critical physiological process closely linked to aging. The accumulation of DNA damage in renal proximal tubular epithelial cells (PTEC) is related to a decline in kidney function. Here, we report that DNA double-strand breaks in PTECs lead to systemic metabolic dysfunction, including weight loss, reduced fat mass, impaired glucose tolerance with mitochondrial dysfunction, and increased inflammation in adipose tissues and the liver. Single-cell RNA sequencing analysis...

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CONCLUSIONS: This study highlights that HCBS have not been fully utilised and are influenced by various factors. Moving forward, it is crucial to address the care needs of different income groups, with particular attention to the unique challenges faced by rural older adults. Targeted policies and interventions are necessary to enhance accessibility for those with chronic illnesses and limited family support. Local governments should work in partnership with families to develop higher-quality,...

The quality and quantity of the ovarian reserve are meticulously regulated through various cell death pathways to guarantee the availability of high-quality oocytes for fertilization. While apoptosis is recognized for contributing to maintaining ovarian reserve, the involvement of other cell death pathways remains unclear. Employing chemical genetics and proteomics, this study reveals the crucial involvement of Cathepsin B in maintaining the ovarian reserve. Results indicate that apoptosis and...

CONCLUSION: Decomposing the power spectrum into periodic and aperiodic components allows for the characterization of age-related changes.

Immune resilience as a salutogenic force to preserve healthspan and resilience to challenges. The figure was created with BioRender (https://www.BioRender.com/).

Age is a primary risk factor for chronic conditions, including age-related macular degeneration (AMD). Impairments in autophagy processes are implicated in AMD progression, but the extent of autophagy's contribution and its therapeutic potential remain ambiguous. This study investigated age-associated transcriptomic changes in autophagy pathways in the retinal pigment epithelium (RPE) and evaluated the protective effects of topical trehalose, an autophagy-enhancing small molecule, against...

CONCLUSIONS: The frailty index was cross-sectionally associated with EAA, while only GrimAge and DunedinPoAm38 EAA predicted changes in the frailty index. More research is needed to understand the interplay between pathways.