Aging & Longevity

Although subsets with immunosuppressive properties exist, neutrophils are typically known for their pro-inflammatory role and pathogen clearance capabilities. Here, we reveal that neutrophils can paradoxically aid in resolving inflammation by actively producing anti-inflammatory extracellular vesicles. These large aging-neutrophil-derived vesicles (LAND-Vs) do not fit into classical vesicle categorizations due to their specific size, structure, or biogenesis pathway. They are protected from...

CONCLUSIONS: This Delphi study estimated that dementia already affects roughly 1 in 12 older Brazilians aged 60 and above, with slightly higher prevalence in women and significant geographical variations. These results underscore the urgency for targeted public health strategies in Brazil and offer a framework for similar challenges in other LMICs, especially given that dementia cases are projected to increase by approximately 3.6 times in 4 decades.

Cumulative silicon photovoltaic (PV) waste highlights the importance of considering waste recycling before the commercialization of emerging PV technologies^(1,2). Perovskite PVs are a promising next-generation technology³, in which recycling their end-of-life waste can reduce the toxic waste and retain resources^(4,5). Here we report a low-cost, green-solvent-based holistic recycling strategy to restore all valuable components from perovskite PV waste. We develop an efficient aqueous-based...

In multiple sclerosis (MS), inflammation of the central nervous system results in demyelination, neuroaxonal injury, and cell death. However, the molecular signals responsible for injury and cell death in neurons are not fully characterized. Here, we profile the transcriptome of retinal ganglion cells (RGCs) in experimental autoimmune encephalomyelitis (EAE) mice. Pathway analysis identifies a transcriptional signature reminiscent of aged RGCs with some senescent features, with a comparable...

The limited success of cancer immunotherapy has posed challenges in treating patients with cancer. However, promising strides could be made with a deeper understanding of the factors that cause T cell dysfunction within the tumor microenvironment and by developing effective strategies to counteract tumor-induced immune suppression. Here, we report that tumor-derived extracellular vesicles (tEVs) can induce senescence and suppression in T cells. Programmed death ligand 1 (PD-L1), a key component...

DNA topoisomerases are essential molecular machines that manage DNA topology in the cell and play important roles in DNA replication and transcription. We found that knocking down the enzyme topoisomerase Top2 or its mammalian homolog TOP2B increases the lifespan of S. cerevisiae, C. elegans, and mice. TOP2B reduction also extends the health span of mice and alleviates the pathologies of aging in multiple tissues. At the cellular/molecular level, TOP2B reduction alleviates the major hallmarks of...

Dementia, characterized by loss of cognitive abilities in the elderly, poses a significant global health challenge. This study explores the role of astrocytes, one of most representative glial cells in the brain, in mitigating cognitive decline. Specifically, we investigated the impact of Hevin (also known as SPARC-like1/SPARCL-1), a secreted glycoprotein, on cognitive decline in both normal and pathological brain aging. By using adeno-associated viruses, we overexpressed Hevin in hippocampal...

Despite advances in treatment, the prognosis for patients with pulmonary arterial hypertension (PAH) remains dismal, highlighting the need for further therapeutic advances. By using RNA sequencing on pulmonary artery smooth muscle cells (PASMCs), functional enrichment, and connectivity map analyses, we identify Aurora kinase B (AURKB) as a candidate therapeutic target. We show that AURKB inhibition blocks cell cycle progression and reverses the gene signature of PAH-PASMCs. We also report that...

Aging-related muscle atrophy and weakness contribute to loss of mobility, falls, and disability. Mitochondrial dysfunction is widely considered a key contributing mechanism to muscle aging. However, mounting evidence positions physical activity as a confounding factor, making unclear whether muscle mitochondria accumulate bona fide defects with aging. To disentangle aging from physical activity-related mitochondrial adaptations, we functionally profiled skeletal muscle mitochondria in 51...

Ribophagy is a selective autophagic process that regulates ribosome turnover. Although NUFIP1 has been identified as a mammalian receptor for ribophagy, its homologues do not exist in yeast and nematodes. Here we demonstrate that Rpl12, a ribosomal large subunit protein, functions as a conserved ribophagy receptor in multiple organisms. Disruption of Rpl12-Atg8s binding leads to significant accumulation of ribosomal proteins and rRNA, while Atg1-mediated Rpl12 phosphorylation enhances its...

Loss of epigenetic information during physiological aging compromises cellular identity, leading to de-repression of developmental genes. Here, we assessed the epigenomic landscape of vulnerable neurons in two reference mouse models of Huntington neurodegenerative disease (HD), using cell-type-specific multi-omics, including temporal analysis at three disease stages via FANS-CUT&Tag. We show accelerated de-repression of developmental genes in HD striatal neurons, involving histone re-acetylation...

The ovary is one of the first organs in humans to exhibit age-related functional impairments. As an organ composed of diverse heterogeneous cell types, the ovary exhibits cell-type-specific changes during the aging process, ultimately leading to a decline in female fertility. Investigating the molecular mechanisms of ovarian aging is crucial for understanding age-related fertility dysfunction in females. In this study, we combine scRNA-seq and scATAC-seq from mouse young/aged ovaries to...

CONCLUSION: This study demonstrates a negative and non-linear association between dietary live microbe intake and frailty in older adults. These findings provide evidence of a potential link between live microbe intake and frailty, warranting further longitudinal and interventional studies to explore this relationship and its implications for healthy aging.

Inactivation of telomerase (TERT) in adipocyte progenitor cells (APC) expedites telomere attrition, and the onset of diabetes in mice fed high-fat diet (HFD), which promotes APC over-proliferation and replicative senescence. Here, we show that time-restricted feeding or caloric restriction in the postnatal development of mice subsequently subjected to HFD prevents telomere attrition but not glucose intolerance. This metabolic effect of dietary intervention was not observed for mice with TERT KO...

Despite the high prevalence of age-dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. We investigated the efficacy of long-term oral K(3)Citrate supplementation in ameliorating disc calcification in LG/J mice, a model of spontaneous age-associated disc calcification. K(3)Citrate reduced the incidence of disc calcification without affecting the vertebral bone structure, knee calcification, plasma chemistry, or locomotion in...

Skin aging represents a multifactorial process influenced by both intrinsic and extrinsic factors, collectively known as the skin exposome. Cellular senescence, characterized by stable cell cycle arrest and secretion of pro-inflammatory molecules, has been implicated as a key driver of physiological and pathological skin aging. Increasing evidence points towards the role of senescence in a variety of dermatological diseases, where the accumulation of senescent cells in the epidermis and dermis...

Ensuring long-term reliable contacts in thermoelectric devices is particularly challenging due to their operation under high temperatures and has been one of the large obstacles in the field for application. Typically, thermodynamically driven atomic diffusion and reactions often degrade the contacts, leading to increased contact resistivity and ultimately limiting the device's lifespan. Here, we report an unconventional self-optimized contact resistivity mechanism in the Sb/MgAgSb junction. Mg...

Breast cancer is a leading cause of mortality worldwide. Pharmacological inhibitors of cyclin-dependent kinases (CDK) 4 and 6 (CDK4/6i) inhibit breast cancer growth by inducing a senescent-like state. However, the long-term treatment efficacy remains limited by the development of drug resistance, so clearance of senescent-like cancer cells may extend the durability of treatment. However, we show here that while CDK4/6i-treated breast cancer cells exhibit various senescence-associated phenotypes,...

Chronic, low-grade inflammation is a hallmark of aging and various age-related diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). The prevalence of metabolic dysfunction-associated steatohepatitis (MASH), an advanced form of MASLD, increases with age and contributes to morbidity and mortality among the elderly. This study investigates the role of necroptosis, a programmed cell death pathway that promotes inflammation, in liver inflammaging and age-associated...

Alzheimer's disease (AD) can be identified through biomarkers of amyloid (A) and tau (T) pathology. Frailty, a measure of biological aging, could impact the association between AD neuropathology and its clinical manifestation. We aimed to investigate the relationship between frailty and AD biomarkers among people with mild cognitive impairment (MCI) attending a university memory clinic. Data were collected from a cohort of patients with MCI at the Memory Center of Geneva University Hospital...