Aging & Longevity

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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CONCLUSION: Losing 15% or more of neuromuscular strength reduces walking speed over time. Therefore, monitoring the percentage change in NS can serve as a useful tool for early detection of the risk of WS decline, allowing for more personalised clinical investigations and timely neuromuscular strengthening interventions to minimise adverse effects on mobility in older adults.

CONCLUSIONS: IFN-β administration to IAV-infected old mice improved overall outcome without worsening lung damage and inhibited neuroinflammatory and brain damage-associated pathways. These results suggest IFN-β warrants further investigation as adjunctive treatment for severe viral infections in select hosts.

To develop and validate a parsimonious risk model for short-term memory decline in older adults and to evaluate its cross-population transportability between Chinese and Japanese cohorts. The model was developed in 5985 cognitively normal older adults from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015). Seven machine learning algorithms were compared, and a Cox proportional hazards (CoxPH) model was selected for its optimal balance between performance and parsimony. The...

Intervertebral Disc Degeneration (IDD) is a common degenerative spinal disease and a leading cause of low back pain and disability. The senescence of nucleus pulposus cells (NPCs) is a central mechanism driving the pathological progression of IDD, though its regulatory mechanisms remain unclear. Bioinformatic analysis identified FGF21 as a key gene regulating NPCs senescence. In both human and rat degenerated intervertebral discs, FGF21 expression was significantly downregulated and closely...

Hematopoietic stem cells (HSCs) self-renew and differentiate into all blood cells maintaining the hematopoietic system. Age-related HSC dysfunction impacts all of hematopoiesis, with DNA methylation alterations in aged HSCs contributing to altered function. Growth Arrest and DNA Damage-inducible proteins (Gadd45a, Gadd45b, and Gadd45g) are expressed in HSC activation, and Gadd45b has been reported to induce DNA demethylation. Thus, we explored the relationship between Gadd45b, DNA methylation...

The rapidly developing search engines for glycopeptide identification and accumulated high-resolution glycoproteomic data underscore the need for robust downstream data mining platforms towards subsequently functional and mechanistic studies. Here, we introduce StrucGAP, a Structural Glycoproteomics Analysis Platform for scalable downstream data mining of site-specific N-glycoproteomics. It integrates modules for data quality control, overall glycan structural characterization, altered glycan...