Aging & Longevity

DNA replication stress responses are guardians of genomic stability critical during development, hematopoiesis, cancer therapy response, aging and disease suppression. Central to these responses are reversed forks (RF), which are distinct four-way DNA structures formed during DNA replication stalling to protect against toxic DNA lesions. Historically, RF detection relies on specialized electron microscopy, precluding studies within their native cellular context. By harnessing intrinsic...

CONCLUSIONS: We propose that aging affects RFT performance through two dissociable mechanisms. A general decline in multisensory integration increases overall errors symmetrically across tilt angles. The clockwise-specific asymmetry, by contrast, may reflect age-related changes in lateralized visuospatial attention-specifically, the well-documented rightward attentional shift that accompanies healthy aging-which differentially affects the weighting of visual cues for clockwise vs....

Cognitive impairment associated with obstructive sleep apnea (OSA) is more prevalent and severe in the elderly, possibly due to age-related increases in neuronal susceptibility to intermittent hypoxia (IH). As telomere dysfunction is a key driver of cellular aging, this study aimed to characterize the interaction between telomere dysfunction and IH, and to explore the associated molecular alterations. Using telomere-damaged PC12 cells and G3 Tert^(-/-) progeria mice exposed to IH, we assessed...

OBJECTIVE: Cerebral microbleeds (CMBs) are small vascular lesions detectable on MRI and are associated with increased stroke risk and cognitive decline. However, imaging-based diagnosis is limited by cost and accessibility. This study aimed to identify serum protein biomarkers for early CMB diagnosis and to elucidate molecular mechanisms underlying CMB subtypes.

Cognitive aging is a highly heterogeneous process, with some individuals preserving stable cognitive performance across the lifespan while others exhibiting pronounced decline. This marked interindividual variability indicates that chronological age alone is a poor predictor of cognitive health. Rather than reflecting uniform degeneration, cognitive aging emerges from divergent biological trajectories spanning molecular, cellular, and network levels. In this review, we synthesize emerging...

Macrophages serve as major defenders against pathogens, playing a crucial role in the initiation and modulation of immune responses. Age-related decline in macrophage functions is attributed to a complex network of cellular senescence and immunosenescence. The onset of cellular senescence is often a consequence of sustained oxidative stress, which is worsened by immunosenescence. Green tea catechin, epigallocatechin gallate (EGCG), has emerged as a promising candidate for promoting healthy aging...

Engineering red blood cells (RBCs) has been widely explored for drug delivery, imaging, vaccination, and other applications. However, effective strategies to directly engineer RBCs in vivo are still lacking. Here, we report successful metabolic glycan labeling of RBCs in vivo. We demonstrate that systemically administered azido-sugars can metabolically label circulating RBCs with azido groups, through labeling of both mature RBCs and RBC precursor cells. The surface azido tags on RBCs can...

Cognitive reserve (CR) and brain maintenance (BM) reflect better than expected cognition despite brain pathology and minimal age-related brain changes that explain stable cognition, respectively. Despite being commonly used, joint quantification of these concepts has been limited; our aim is to derive longitudinal CR and BM measures and investigate CR's relationship with education and functional connectivity. We analyzed longitudinal data from 451 participants (241 female, age(mean) = 68.5...

Life expectancy (LE) at birth has increased in many countries throughout the twentieth and twenty-first centuries. Future LE values are estimated by extrapolating existing data. However, it remains difficult to determine the LE limit using mathematical models such as the Kannisto model and the Gompertz function due to significant random fluctuations in centenarian mortality rates. There are 12 biological hallmarks of ageing, including epigenetic changes and senescent cells. These microscopic...

The microbiota of intestinal origin has a significant impact on the aging process, affecting skin health and overall cell longevity. Aging is marked by physiological alterations, such as enhanced oxidative stress, which is intensified by external factors like UV radiation and environmental pollution. The gut microbiota profoundly influences immune functions and results in reduced inflammation, which contributes to the anti-aging process. The present review is an attempt to showcase the current...

The thymus, a primary lymphoid organ essential for lifelong T cell development, undergoes progressive age-related involution. The thymus is innervated by the sympathetic nervous system (SNS), but the extent of innervation and its relationship to the microenvironment or age-related involution remain unclear. Here, we provide a detailed mapping of thymic sympathetic innervation using advanced imaging methods to characterize its distribution and relationship with vascular structures, capsule, and...

Tendon injuries are common and heal poorly, whereas developing tendons repair with minimal scarring; how this capacity declines with age remains poorly understood. Here, we combine histology, single-nucleus, single-cell, and spatial transcriptomic profiling of human Achilles and quadriceps tendons across embryonic, fetal, and adult stages, including ruptured adult tendons. We identify seven embryonic progenitor states that are predicted to contribute to three tendon-associated...

CONCLUSIONS: A balanced MD-based dietary mix preserves renal structure and function in db/db mice by counteracting oxidative stress, mitochondrial dysfunction, and early fibrotic remodeling. These findings support the MD as a potential nutritional strategy to enhance renal resilience and mitigate metabolic stress-induced kidney aging in the context of diabetes and obesity.

Socio-economic status (SES) impacts life-long health from early development to old age. We review SES differences in biological factors that begin before fertilization and extend into later life, 'egg to exit'. SES gradients are shown in onset and prevalence of chronic conditions including cardiovascular disease, diabetes and dementia, leading up to a 15-year difference in life expectancy in some countries. Our analysis is limited to high-income countries and does not include detailed discussion...

CONCLUSION: In older men, RE improved metabolic flexibility. PRO had a limited benefit. No synergistic effects were observed.

Mitochondria play a central role in cellular energy metabolism and homeostasis, and their dysfunction is closely linked to the progression of age-related diseases. The mitochondrial ubiquitin ligase MITOL (also known as MARCHF5) is a key regulator of mitochondrial dynamics and function, and reduced MITOL expression in the mouse heart has been implicated in mitochondrial dysfunction and cardiac aging. In this study, we identified berberrubine as a compound that promotes MITOL expression and...

For women with diminished ovarian reserve or of advanced age, controlled ovarian stimulation presents a significant challenge during in vitro fertilization cycles. This multi-center, open-label, randomized controlled trial enrolled 318 women with diminished ovarian reserve (defined as an antral follicle count < 5 or anti-Müllerian hormone level of 0.1-1.1 ng/mL) or advanced age (40-45 years) between 2020 and 2023. Participants were assigned to either a modified letrozole protocol (mLP, n = 159)...

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Turquoise killifish (Nothobranchius furzeri) are naturally short-lived vertebrates that recapitulate key aspects of human aging. However, the molecular and cellular causes of systemic aging in killifish are poorly understood. Here we ask whether killifish undergo age-dependent changes in the main hematopoietic organ (kidney marrow), which may contribute to systemic aging. To characterize immune aging in killifish, we used single-cell RNA sequencing, cytometry and functional in vitro assays on...

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