Aging & Longevity

The elimination of senescent cells can enhance the osteointegration of implants in elderly patients. However, achieving specific clearance of senescent cells without adversely affecting the function of normal cells remains challenging. Here we show an implant surface modification technique to achieve specific clearance of locally senescent cells by modulating their metabolism. Our method involve modifying implants with BPTES, a glutaminase 1 (GLS1) inhibitor, through π-π stacking with dopamine....

While coastal renewable energy-powered seawater electrolysis is highly promising for green H(2) production, the anodic chemical corrosion by aggressive chlorine chemistry and violent bubble release-induced physical damage to anodes are two long-standing issues that lead to inferior stability. Here we pursue integrating triple protection to a monolithic catalyst to concurrently alleviate chlorine chemistry and weaken external forces from bubble escaping/collapsing. The 1^(st) and 2^(nd) defenses...

As a powerful oxidant, atomic oxygen (O) holds considerable promise for a variety of biomedical and industrial applications. However, the inability to quantify solvated oxygen atoms has prevented the determination of the fundamental parameters governing its behaviour in relevant aqueous environments. Here, we directly image ground-state oxygen atoms in water using femtosecond two-photon absorption laser-induced fluorescence. Measurements show that oxygen atoms persist for tens of microseconds in...

Mammalian maximum lifespan (MLS) varies over a hundred-fold, yet the molecular mechanisms underlying this diversity remain unclear. We present a cross-species analysis of alternative splicing (AS) across six tissues in 26 mammals, identifying hundreds of conserved AS events significantly associated with MLS, with the brain containing twice as many tissue-specific events as peripheral tissues. MLS-AS events are enriched in pathways related to mRNA processing, stress response, neuronal functions,...

Age-associated decline in tissue NAD^(+) levels contribute to functional impairments, recognized as aging. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme crucial for NAD^(+) biosynthesis in mammals, is encapsulated in extracellular vesicles (EVs) and secreted into the bloodstream. The importance of extracellular NAMPT-containing EVs (eNAMPT-EVs) in hypothalamic NAD^(+) biosynthesis has been demonstrated in several mouse models. However, whether eNAMPT-EVs derived from...

Skeletal muscle is essential for movement, respiration, and metabolism, with mTORC1 acting as a key regulator of protein synthesis and degradation. In aging muscle, mTORC1 becomes overactivated, contributing to sarcopenia, though the mechanisms remain unclear. Here, we identify DEAF1, a FOXO-regulated transcription factor, as a key upstream driver of mTORC1 in aged muscle. Elevated Deaf1 expression increases mTOR transcription, leading to heightened mTORC1 activity, impaired proteostasis, and...

Fusidic acid (FA) is one of few remaining antibiotics active against Methicillin-resistant Staphylococcus aureus. FusB confers resistance to FA by rescuing the translocation factor Elongation Factor-G (EF-G) from FA-stalled ribosome complexes. FusB induces allosteric effects on dynamics in EF-G, causing significant changes in the conformational flexibility of domain III that result in an increase in a minor, more disordered state, overcoming the steric block induced by FA. We show that...

During brain aging, terminally differentiated neuroglia exhibit metabolic dysfunction and increased oxidative damage, compromising their function. These cellular and molecular alterations impair their ability to maintain myelin sheath integrity, contributing to age-related white matter degradation. Calorie restriction (CR) is a well-established intervention that can slow biological aging and may reduce age-related metabolic alterations, thereby preserving the molecular function of aging glia....

Cellular senescence and necroptosis are two cell fates, which trigger an inflammatory response and increase with age, that have been proposed to play a role in inflammaging. In this study, we performed the first study to directly test the possible interaction between necroptosis and cellular senescence. Using a novel Mlkl-KI mouse model, we were able to specifically induce (~ 4-fold) the overexpression of MLKL, the necroptotic executioner, in hepatocytes (hMlkl-KI mice). The overexpression of...

Bone marrow exhibits functional decline, yet cellular heterogeneity and molecular mechanisms remain unclear due to limitations of traditional research methods. This study aims to characterize age-related changes and identify key drivers in bone marrow. Integrated multi-omics analysis was performed using scRNA-seq, proteomics, pseudo-bulk transcriptomics, weighted gene co-expression network analysis (WGCNA)-based transcription factor (TF) network modeling, and CellChat analysis. Samples included...

The human brain is one of the most metabolically active tissues in the body, due in large part to the activity of trillions of synaptic connections. Under normal conditions, macroautophagy/autophagy at the synapse plays a crucial role in synaptic pruning and plasticity, which occurs physiologically in the absence of disease- or aging-related stressors. Disruption of autophagy has profound effects on neuron development, structure, function, and survival. Neurons are dependent upon maintaining...

Preovulatory follicle aging is the period between formation and ovulation of a mature follicle. Previous studies had shown that mammalian preovulatory follicle aging is associated with chromosomal abnormalities and developmental defects such as decreased implantation, increased malformation and mortality and lower embryonic weight. Our understanding of the molecular events governing this process has been hampered by the difficulty in accessing them in vivo under natural conditions. We...

Type 2 diabetes mellitus (T2DM) is increasingly recognized as a shared pathological substrate for both sarcopenia and cognitive decline, particularly Alzheimer's disease (AD). This review synthesizes current evidence on the converging molecular pathways linking insulin resistance, hyperglycaemia, mitochondrial dysfunction, oxidative stress, and chronic inflammation to muscle wasting and neurodegeneration. Central to this interplay is the muscle-brain axis, a bidirectional communication network...

Meibomian gland dysfunction (MGD) is the leading cause of Dry Eye Disease (DED), accounting for approximately 90% of DED cases worldwide. The transcription factor KROX20 has been shown to mark stem cells that play a critical role in Meibomian gland (MG) development and homeostasis, however, the molecular mechanisms underlying these processes are not well understood. In this report, we used multiple Krox20 lineage tracing and ablation studies to investigate lineage commitment during MG...

Gait performance depends on numerous aspects of brain functioning that are also relevant to key cognitive processes throughout the lifespan. The Timed Up and Go (TUG) test has been shown to be a reliable tool for assessing age-related mobility changes and risk of falls in older adults. This study aimed to predict TUG performance using motor-cognitive inter-network connectivity, cognitive performance and socio-demographics. 189 participants without cognitive impairment were included. Mobility was...

The lifespan of most eukaryotic mRNAs is modulated by the gradual shortening of the poly(A) tail and removal of the associated poly(A)-binding protein. The human PAN2-PAN3 complex catalyzes initial deadenylation by shortening long poly(A) tails associated with PABPC1. Both PAN2-PAN3 and PABPC1 are evolutionarily conserved from fungi to humans. How the human complex has adapted to recognize and act on longer poly(A) tails characteristic of mammalian mRNAs remains unclear. Here, we report a method...

Astrocytes play essential roles in the brain, and their dysfunction is associated with nearly every form of neurological disease. Despite their ubiquity, knowledge of how astrocytes contribute to disease pathogenesis is incomplete; accordingly, harnessing their biology toward therapeutics remains a major challenge. Here we show that the transcription factor Sox9 plays a context-specific role in maintaining astrocyte function and circuit activity in the aging hippocampus and Alzheimer's disease...

CONCLUSION: The Dubousset Functional Test demonstrated relatively good psychometric properties for geriatric functional assessment.

CONCLUSIONS: Health service utilisation among older adults in Tamale was associated with a combination of predisposing, enabling, and need factors. While insurance coverage was high and contributed to health service utilisation, self-employment and living more than 4 km from a facility were major barriers. Community-based outreach, including mobile health clinics or targeted home-based care, may be a cost-effective approach to improving older adults’ access to and utilisation of health services.

CONCLUSIONS: This review highlights the potential of PCC in enhancing the quality of care for older adults in outpatient settings. Building on our findings, a phased approach focusing on older adults with multimorbidity is recommended for LMICs like Iran, with an emphasis on integrating both primary and specialized care. Our proposed seven-dimensional PCC model includes access to care, proactive care, patient empowerment, integration into care pathways, a whole-person approach, coordinated care,...