Aging & Longevity

Ribbon synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs) in the inner ear are damaged by noise trauma and with aging, causing "synaptopathy" and hearing loss. Cocultures of neonatal denervated organs of Corti and newly introduced SGNs have been developed to find strategies for improving IHC synapse regeneration, but evidence of the physiological normality of regenerated synapses is missing. This study utilizes IHC optogenetic stimulation and SGN recordings,...

Presbycusis is a prevalent condition in older adults characterized by the progressive loss of hearing due to age-related changes in the cochlea, the auditory portion of the inner ear. Many adults also struggle with understanding speech in noise despite having normal auditory thresholds, a condition termed "hidden" hearing loss because it evades standard audiological assessments. Examination of animal models and postmortem human tissue suggests that hidden hearing loss is also associated with...

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The ever-increasing power conversion efficiency of perovskite solar cells has illuminated the future of the photovoltaic industry, but the development of commercial devices is hampered by their poor stability. In this study, we report a scalable stabilization method using vapor-phase fluoride treatment, which achieves 18.1%-efficient solar modules (228 square centimeters) with accelerated aging-projected T(80) lifetimes (time to 80% of efficiency remaining) of 43,000 ± 9000 hours under 1-sun...

Iron-based hexacyanoferrate (Fe-HCF) are promising cathode materials for sodium-ion batteries (SIBs) due to their unique open-channel structure that facilitates fast ion transport and framework stability. However, practical implementation of SIBs has been hindered by low initial Coulombic efficiency (ICE), poor rate performance, and short lifespan. Herein, we report a coordination engineering to synthesize sodium-rich Fe-HCF as cathodes for SIBs through a uniquely designed 10-kg-scale chemical...

The reduced ability of the central nervous system to regenerate with increasing age limits functional recovery following demyelinating injury. Previous work has shown that myelin debris can overwhelm the metabolic capacity of microglia, thereby impeding tissue regeneration in aging, but the underlying mechanisms are unknown. In a model of demyelination, we found that a substantial number of genes that were not effectively activated in aged myeloid cells displayed epigenetic modifications...

Frailty, a multidimensional indicator of suboptimal aging, reflects cumulative declines across multiple physiological systems. Although age-related changes have been reported in gut microbiota, their role in healthy aging remains unclear. In this study, we calculated frailty index (FI) from 33 health-related items to reflect the overall health status of 1,821 older adults (62-96 years, 55% female) and conducted multi-omics analysis using gut metagenomic sequencing data and plasma metabolomic...

In Latin America and the Caribbean (LAC), sociodemographic context, socioeconomic disparities and the high level of urbanization provide a unique entry point to reflect on the burden of cardiometabolic disease in the region. Cardiovascular diseases are the main cause of death in LAC, precipitated by population growth and ageing together with a rapid increase in the prevalence of cardiometabolic risk factors, predominantly obesity and diabetes mellitus, over the past four decades. Strategies to...

Microglia are necessary for central nervous system (CNS) function during development and play roles in ageing, Alzheimer's disease and the response to demyelinating injury^(1-5). The mitochondrial respiratory chain (RC) is necessary for conventional T cell proliferation⁶ and macrophage-dependent immune responses^(7-10). However, whether mitochondrial RC is essential for microglia proliferation or function is not known. We conditionally deleted the mitochondrial complex III subunit Uqcrfs1...

Cell size is tightly controlled in healthy tissues and single-celled organisms, but it remains unclear how cell size influences physiology. Increasing cell size was recently shown to remodel the proteomes of cultured human cells, demonstrating that large and small cells of the same type can be compositionally different. In the present study, we utilize the natural heterogeneity of hepatocyte ploidy and yeast genetics to establish that the ploidy-to-cell size ratio is a highly conserved...

Alzheimer's disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood^(1-3). Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1.3 million cells from 283 post-mortem human brain samples across 48 individuals with and without Alzheimer's disease. We identify 76 cell types, including region-specific subtypes of astrocytes and...

Molecule-based selective contacts have become a crucial component to ensure high-efficiency inverted perovskite solar cells^(1-5). These molecules always consist of a conjugated core with heteroatom substitution to render the desirable carrier-transport capability^(6-9). So far, the design of successful conjugation cores has been limited to two N-substituted π-conjugated structures, carbazole and triphenylamine, with molecular optimization evolving around their derivatives^(2,5,10-12). However,...

Living mammal groups exhibit rapid juvenile growth with a cessation of growth in adulthood¹. Understanding the emergence of this pattern in the earliest mammaliaforms (mammals and their closest extinct relatives) is hindered by a paucity of fossils representing juvenile individuals. We report exceptionally complete juvenile and adult specimens of the Middle Jurassic docodontan Krusatodon, providing anatomical data and insights into the life history of early diverging mammaliaforms. We used...

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Alternative day fasting (ADF) has been shown to enhance the lifespan of animals. However, human trials evaluating the efficacy of ADF have only recently emerged, presenting challenges due to the extreme nature of this dietary regimen. To better understand the effects of ADF, we investigated its impact using Caenorhabditis elegans as a model organism. Our findings reveal that ADF extends the lifespan of worms nourished on animal-based protein source, while those fed with plant-based protein as...

Over a lifetime, hematopoietic stem and progenitor cells (HSPCs) are forced to repeatedly proliferate to maintain hematopoiesis, increasing their susceptibility to DNA damaging replication stress. However, the proteins that mitigate this stress, protect HSPC replication, and prevent aging-driven dysregulation are unknown. We report two evolutionarily conserved, ubiquitously expressed chromatin remodeling enzymes with similar DNA replication fork reversal biochemical functions, Zranb3 and...

Autophagy impairment in Huntington disease (HD) has been reported for almost two decades. However, the molecular mechanisms underlying this phenomenon are still unclear. This is partially because it is challenging to model the impact of the disease-causing mutation, aging, as well as the selective vulnerability of neurons in a single model. Recently developed direct neuronal reprogramming that allows researchers to induce neurons-of-interest retaining biological aging information made it...

It is vital to explore effective ways for prolonging electrode lifespans under harsh electrolysis conditions, such as high current densities, acid environment, and impure water source. Here we report alternating electrolysis approaches that realize promptly and regularly repair/maintenance and concurrent bubble evolution. Electrode lifespans are improved by co-action of Fe group elemental ions and alkali metal cations, especially a unique Co^(2+)-Na^(+) combo. A commercial Ni foam sustains...

How hematopoietic stem cells (HSCs) maintain metabolic homeostasis to support tissue repair and regeneration throughout the lifespan is elusive. Here, we show that CD38, an NAD^(+)-dependent metabolic enzyme, promotes HSC proliferation by inducing mitochondrial Ca^(2+) influx and mitochondrial metabolism in young mice. Conversely, aberrant CD38 upregulation during aging is a driver of HSC deterioration in aged mice due to dysregulated NAD^(+) metabolism and compromised mitochondrial stress...

The senescent microenvironment and aged cells per se contribute to tissue remodeling, chronic inflammation, and age-associated dysfunction. However, the metabolic and epigenomic bases of the senescence-associated secretory phenotype (SASP) remain largely unknown. Here, we show that ATP-citrate lyase (ACLY), a key enzyme in acetyl-coenzyme A (CoA) synthesis, is essential for the pro-inflammatory SASP, independent of persistent growth arrest in senescent cells. Citrate-derived acetyl-CoA...