Aging & Longevity

The global aging trend underscores the urgent need for innovative interventions against aging-related decline. Accumulating evidence identifies Akkermansia muciniphila (A. muciniphila) as a key gut microbiota regulator of aging, with its depletion associated with age-related diseases (ARDs), whereas its abundance is enriched in healthy centenarians. This review summarized current evidence linking A. muciniphila to aging, examining their causal relationship, the roles of its bioactive...

Although aging and cancer share complex molecular mechanisms, distinguishing causative factors from byproducts remains challenging. Here, we investigated the role of tissue transcriptomic entropy-a measure of transcriptional disorder-in aging and cancer processes by analyzing RNA-sequencing data from over 25,000 samples from human and mouse tissues. We found that entropy changes during aging are highly tissue-specific, with some tissues showing increased entropy while others exhibit decreased or...

Protein posttranslational modifications (PTMs) play a central role for regulating protein function and cellular processes, with many PTMs arising from reactions with electrophilic metabolites. Here we extend the known landscape of PTMs with the identification of "lysine C(3)-iminylation," the conjugation of protein lysine residues with propionaldehyde. To stabilize iminylation for mass spectrometric analyses and distinguish it from other isomeric PTMs, we developed a fixation and stable-isotope...

Mitohormesis, whereby transient mitochondrial stress induces adaptive signaling, promotes organismal resilience and longevity in invertebrates, but how this operates in mammals and the underlying metabolic signals involved remain unclear. Using a mouse model of mitohormesis, we show that transient mitochondrial superoxide stress during embryogenesis reprograms the adult heart to enhance mitochondrial biogenesis and antioxidant capacity. These adaptations confer protection against mitochondrial...

Mitochondrial DNA (mtDNA) mutations accumulate with age, but their mechanistic contribution to aging remains unclear. The classical mtDNA mutator mouse expresses a proofreading-deficient mtDNA polymerase (POLG^(D257A)) and accumulates mtDNA mutations across all tissues leading to premature aging. However, this model cannot resolve whether the aging phenotype results from systemic dysfunction or cell-intrinsic effects of somatic mtDNA mutations. To overcome this limitation, we generated...

Photochemical oxidation in the aqueous phase is critical for chemical evolution of secondary organic aerosols (SOA), but it represents one of the most uncertain processes in aerosols and clouds. Here, we show that photoirradiation of SOA derived from biomass burning precursors leads to substantial formation of superoxide. The combination of laboratory measurements and kinetic modeling reveals that superoxide generation is driven by photosensitization reactions in aromatic SOA, while the dominant...

Seed longevity (SL) is vital for ensuring food security worldwide. However, the genetic basis of SL has been scarcely documented. Here, we report the cloning of a major SL locus, qSL6, encoding a fatty acyl-ACP thioesterase type B. SL6 is functionally conserved in regulating palmitic acid synthesis in seeds, conferring higher oxidation durability and SL in various species. Through the VP1-SL6 module, a seed desiccation-derived ABA signal is transmitted via VP1, which directly activates SL6...

INTRODUCTION: Population ageing has increased the prevalence of dementia, often accompanied by mobility impairments. It is essential to develop effective interventions and promote adherence among people with dementia. Culturally meaningful activities may enhance motivation, engagement, and rehabilitation outcomes.

Complement comprises a group of plasma and membrane proteins that provide an effective bridging function for innate and adaptive humoral immunity. Understanding complement pathophysiology is fundamental given that inappropriate complement function in host defence can lead to infectious diseases and inefficient disposal of altered, damaged or senescent cells can lead to or enhance autoimmune neurological processes. Although the rising number of approved drugs targeting complement pathways remains...

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While numerous improvements in cycling stability have been demonstrated for next-generation battery chemistries with metallic anodes, their calendar aging (e.g., capacity loss during idle periods of rest) performance painfully lags behind and remains a critical bottleneck hindering their practical deployment. In contrast to their commercial counterparts, metallic anodes exhibit substantial capacity loss during calendar aging. Despite several recent studies exploring the underlying reasons for...

Peto's paradox underscores the puzzling disconnect between organismal lifespan, body size, and cancer incidence. Here, we investigate this relationship by examining the evolutionary rates of human cancer-associated sites across 58 mammalian species. While overall evolutionary rates at cancer-associated loci do not differ significantly between long-lived and short-lived species, cancer-associated sites show greater evolutionary conservation relative to non-cancer sites within long-lived mammals...

Plasma pTau217 is a leading biomarker for Alzheimer's disease, but evidence from genetically admixed populations in low- and middle-income countries remains limited. We evaluated the diagnostic performance of pTau217 and pTau217/Aβ42 measured using Simoa technology in memory-clinic cohorts from Brazil (Cog-Aging-Study, n = 353) and Argentina (GeNED.ar, n = 134). Here we show that both biomarkers accurately identified cerebrospinal fluid (CSF)-defined amyloid pathology in Cog-Aging-Study-Brazil...

Reactive oxygen species (ROS) have been demonstrated to play central functions as signaling molecules thus extending their role beyond oxidative stress in disease and aging. At inhibitory synapses the scaffolding protein gephyrin clusters glycine and GABA type A receptors. Postsynaptic gephyrin clustering is regulated by post-translational modifications such as phosphorylation, S-palmitoylation, and S-nitrosylation, which all critically impact its scaffolding function. Here, we show that...

CONCLUSIONS AND IMPLICATIONS: These findings suggest that HCBS as an aggregate service category is not associated with reduced elder abuse. Future research is needed to examine the role of individual services in elder abuse prevention.

CONCLUSIONS AND IMPLICATIONS: The evidence is uncertain about the effect of initial EHC participation on the 5-year risk of functional disability or death; the point estimate is compatible with a modest benefit, but the 95% CI included the null. These findings neither support expansion nor justify discontinuation of the EHC program for preventing entry into LTC, and call for replication in additional cohorts before policy changes are considered.

Many older adults prefer aging in place, but complex medical and social care needs and fragmented care systems are barriers to maintaining independence at home. Choose Home was implemented at the Veteran Affairs Boston Health Care System in September 2023 to address a critical care gap for patients who seek to remain independent at home but are at high risk for acute care hospitalizations and institutionalization in long-term care facilities. This report describes a subpopulation (n = 16) of...

The metabolic mechanisms by which aging blunts CD8^(+) T cell antitumor and pathogen defense remain unknown. We demonstrate that the aged microenvironment induces CD8^(+) T cell exhaustion by reducing β-hydroxybutyrate (3HB) bioavailability. Aging represses hepatic BDH1-dependent 3HB synthesis, restricting SLC16A1-mediated 3HB uptake. Hepatic BDH1 ablation recapitulates age-associated CD8^(+) T cell dysfunction, compromising antiviral and antitumor immunity, whereas 3HB supplementation reverses...

Asymptomatic infections are traditionally considered harmless, reflecting effective immune control and the absence of clinical disease. Yet growing evidence shows that these silent encounters with microbes are far from being immunologically neutral. Throughout life, humans are challenged by a remarkably broad spectrum of viruses and bacteria, including latent pathogens that persist, fluctuate, or periodically reactivate without producing significant symptoms. From an evolutionary standpoint,...