Aging & Longevity

Ageing dampens the regenerative potential of intestinal epithelium across species including humans, yet the underlying causes remain elusive. Here we characterized the temporal dynamics of regeneration following injury induced by 5-fluorouracil, a commonly used chemotherapeutic agent, using proteomic and metabolomic profiling of intestinal tissues together with functional assays. The comparison of regeneration dynamics in mice of different ages revealed the emergence of proteostasis stress and...

Alzheimer's disease causes progressive cognitive decline, yet some individuals remain resilient despite developing hallmark pathology. A subset of people with Down syndrome (DS), the most common genetic cause of Alzheimer's disease, demonstrates such resilience. Given the elevated risk of hematopoietic mutations in DS, we hypothesize that certain variants may confer microglial resilience. Here, we introduce a myeloid DS-linked CSF2RB A455D mutation into human pluripotent stem cell-derived...

Biomechanical alterations contribute to the decreased regenerative capacity of hematopoietic stem cells (HSCs) upon aging. RhoA is a key regulator of mechanosignaling, but its role in mechanotransduction in stem cell aging remains unclear. Here we show that murine HSCs respond to increased nuclear envelope (NE) tension by inducing NE translocation of P-cPLA2, which cell-intrinsically activates RhoA. Aged HSCs experience physiologically higher intrinsic NE tension, but reducing RhoA activity...

CONCLUSIONS: Unexpected stopping highlights age-related changes in movement strategy. Older adults shift from a distal-driven braking to proximal, multi-joint co-contraction strategy, characterized by increased hip work, reduced knee work, and greater muscle synergy complexity. This proximal engagement reflects a tradeoff along the stability-efficiency continuum: it enhances safety but increases metabolic cost and postural sway. By disrupting the distal-to-proximal control sequence, this...

Aging and diabetes mellitus (DM) are associated with declines in physical fitness, such as reduced muscle strength, balance, and flexibility, increasing the risk of falls and functional limitations. This pilot study used a quasi-experimental design with pre- and post-intervention assessments to evaluate the effects of a 6-month sensorimotor training (SMT) program on physical fitness in older women with type 2 diabetes. Ten women aged 65 and older were divided into an intervention group (IG, n =...

CONCLUSION: Our study reveals volatility in case numbers post-SARS-CoV-2, with males disproportionately affected. A high proportion of elderly patients take anticoagulants. Among the injured, there is a high rate with cerebral injury. Most fractures occur in exposed facial regions. Ongoing surveillance is essential to address increasing geriatric vulnerability.

CONCLUSIONS: Older adults' perceptions of health-promoting activities were influenced by personal, inter-personal and environmental factors. Contextualizing lifestyle modification programs that address their preferences and real-life situations may facilitate engagement. Older adults may also benefit from future initiatives that empower them to choose among feasible options to increase their self-efficacy for preventing frailty.

CONCLUSIONS: The results of the concept analysis of relocation in older adults revealed a comprehensive insight into this concept. Successful relocation in the older adults is achieved by considering the physical, personal, social, economic, and psychological aspects, and the preparation and planning of the older adults.

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...