Aging, Lifespan & Longevity

Behaviors that rely on the hippocampus are particularly susceptible to chronological aging, with many aged animals (including humans) maintaining cognition at a young adult-like level, but many others the same age showing marked impairments. It is unclear whether the ability to maintain cognition over time is attributable to brain maintenance, sufficient cognitive reserve, compensatory changes in network function, or some combination thereof. While network dysfunction within the hippocampal...

Reduced activity of insulin/insulin-like growth factor signaling (IIS) increases healthy lifespan among diverse animal species. Downstream of IIS, multiple evolutionarily conserved transcription factors (TFs) are required; however, distinct TFs are likely responsible for these effects in different tissues. Here we have asked which TFs can extend healthy lifespan within distinct cell types of the adult nervous system in Drosophila Starting from published single-cell transcriptomic data, we report...

Single-nucleotide variants (SNVs), pertinent to aging and disease, occur sporadically in the human genome, hence necessitating single-cell measurements. However, detection of single-cell SNVs suffers from false positives (FPs) due to intracellular single-stranded DNA damage and the process of whole-genome amplification (WGA). Here, we report a single-cell WGA method termed multiplexed end-tagging amplification of complementary strands (META-CS), which eliminates nearly all FPs by virtue of DNA...

Clinical trials of novel therapeutics for Alzheimer's Disease (AD) have consumed a large amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA) for another indication is a more rapid and less expensive option. We present DRIAD (Drug Repurposing In AD), a machine learning framework that quantifies potential associations between the pathology of AD severity (the Braak stage) and molecular mechanisms as encoded in...

Recent studies have reported a variety of health consequences of climate change. However, the vulnerability of individuals and cities to climate change remains to be evaluated. We project the excess cause-, age-, region-, and education-specific mortality attributable to future high temperatures in 161 Chinese districts/counties using 28 global climate models (GCMs) under two representative concentration pathways (RCPs). To assess the influence of population ageing on the projection of future...

Given the severity of the SARS-CoV-2 pandemic, a major challenge is to rapidly repurpose existing approved drugs for clinical interventions. While a number of data-driven and experimental approaches have been suggested in the context of drug repurposing, a platform that systematically integrates available transcriptomic, proteomic and structural data is missing. More importantly, given that SARS-CoV-2 pathogenicity is highly age-dependent, it is critical to integrate aging signatures into drug...

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary...

Cockayne syndrome (CS) is a segmental premature aging syndrome caused primarily by defects in the CSA or CSB genes. In addition to premature aging, CS patients typically exhibit microcephaly, progressive mental and sensorial retardation and cutaneous photosensitivity. Defects in the CSB gene were initially thought to primarily impair transcription-coupled nucleotide excision repair (TC-NER), predicting a relatively consistent phenotype among CS patients. In contrast, the phenotypes of CS...

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Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types. Results are then meta-analyzed across cohorts. Ten positive...

Aging is a progressive degenerative process involving a chronic low-grade inflammation and the accumulation of senescent cells. One major issue is to reveal the mechanisms which promote the deposition of pro-inflammatory senescent cells within tissues. The accumulation involves mechanisms which increase cellular senescence as well as those inhibiting the clearance of senescent cells from tissues. It is known that a persistent inflammatory state evokes a compensatory immunosuppression which...

Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are...

The mosquito microbiota impacts the physiology of its host and is essential for normal larval development, thereby influencing transmission of vector-borne pathogens. Germ-free mosquitoes generated with current methods show larval stunting and developmental deficits. Therefore, functional studies of the mosquito microbiota have so far mostly been limited to antibiotic treatments of emerging adults. In this study, we introduce a method to produce germ-free Aedes aegypti mosquitoes. It is based on...

T cell rejuvenation by PD-1/PD-L1 blockade, despite emerging as a highly promising therapy for advanced cancers, is only beneficial for a minority of treated patients. There is evidence that a lack of efficient T cell activation may be responsible for the failure. Here, we demonstrate that IL-21 can be targeted to tumor-reactive T cells by fusion of IL-21 to anti-PD-1 antibody. To our surprise, the fusion protein PD-1Ab21 promotes the generation of memory stem T cells (T(SCM)) with enhanced cell...

Integrating the analysis of molecular data from different sources may improve our understanding of the effects of biological aging.

NO(x) abatement has been an indispensable part of environmental catalysis for decades. Selective catalytic reduction with ammonia using V(2)O(5)/TiO(2) is an important technology for removing NO(x) emitted from industrial facilities. However, it has been a huge challenge for the catalyst to operate at low temperatures, because ammonium bisulfate (ABS) forms and causes deactivation by blocking the pores of the catalyst. Here, we report that physically mixed H-Y zeolite effectively protects...

We previously found that B and AGL6 proteins form L (OAP3-2/OAGL6-2/OPI) and SP (OAP3-1/OAGL6-1/OPI) complexes to determine lip/sepal/petal identities in orchids. Here, we show that the functional L' (OAP3-1/OAGL6-2/OPI) and SP' (OAP3-2/OAGL6-1/OPI) complexes likely exist and AP3/PI/AGL6 genes have acquired additional functions during evolution. We demonstrate that the presumed L' complex changes the structure of the lower lateral sepals and helps the lips fit properly in the center of the...

This article reviews some key strands of demographic research on past trends in human longevity and explores possible future trends in life expectancy at birth. Demographic data on age-specific mortality are used to estimate life expectancy, and validated data on exceptional life spans are used to study the maximum length of life. In the countries doing best each year, life expectancy started to increase around 1840 at a pace of almost 2.5 y per decade. This trend has continued until the...

Skeletal aging is a complex process, characterized by a decrease in bone formation, an increase in marrow fat, and stem cell exhaustion. Loss of H3K9me3, a heterochromatin mark, has been proposed to be associated with aging. Here, we report that loss of KDM4B in mesenchymal stromal cells (MSCs) exacerbated skeletal aging and osteoporosis by reducing bone formation and increasing marrow adiposity via increasing H3K9me3. KDM4B epigenetically coordinated β-catenin/Smad1-mediated transcription by...