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Science, Volume 387, Issue 6736, Page 832-832, February 2025.

The latest in science and policy

Stamp-size devices running machine learning models are tackling agricultural, health, and conservation problems in resource-poor regions

“Exceptional” fossil collections housed by the Paleontological Research Institute risk being orphaned

Here’s the story behind the billions in payments to institutions with research grants that NIH wants to cut

Alzheimer's disease (AD) is predominantly the most recurring and devastating neurological condition among the elderly population, characterized by the accumulation of amyloid-β (Aβ) and phosphorylated tau proteins, and is accompanied by progressive decline of learning and memory. Due to its complex and multifactorial etiology, a wide variety of therapeutic interventions have been developed. Despite constant advancements in the field, effective treatments that ameliorate the severity of...

Repurposed drugs provide a rich source of potential therapies for Alzheimer's disease (AD) and other neurodegenerative disorders (NDD). Repurposed drugs have information from non-clinical studies, phase 1 dosing, and safety and tolerability data collected with the original indication. Computational approaches, "omic" studies, drug databases, and electronic medical records help identify candidate therapies. Generic repurposed agents lack intellectual property protection and are rarely advanced to...

Alzheimer's disease (AD) is predominantly the most recurring and devastating neurological condition among the elderly population, characterized by the accumulation of amyloid-β (Aβ) and phosphorylated tau proteins, and is accompanied by progressive decline of learning and memory. Due to its complex and multifactorial etiology, a wide variety of therapeutic interventions have been developed. Despite constant advancements in the field, effective treatments that ameliorate the severity of...

Aging populations worldwide face an increasing burden of age-related chronic conditions, necessitating a deeper understanding of the underlying mechanisms. Purine metabolism has emerged as a crucial player in the pathophysiology of aging, affecting various tissues and organs. Dysregulation of purine metabolism, particularly alterations in extracellular adenosine levels and adenosine receptor signaling, contributes to age-related musculoskeletal problems, cardiovascular diseases, inflammation,...

A fundamental challenge for cancer vaccines is to generate long-lived functional T cells that are specific for tumour antigens. Here we find that mRNA-lipoplex vaccines against somatic mutation-derived neoantigens may solve this challenge in pancreatic ductal adenocarcinoma (PDAC), a lethal cancer with few mutations. At an extended 3.2-year median follow-up from a phase 1 trial of surgery, atezolizumab (PD-L1 inhibitory antibody), autogene cevumeran¹ (individualized neoantigen vaccine with...

Age-related thymic involution precedes aging of all other organs in vertebrates and initiates the process of declining T cell diversity, which leads to eventual immune dysfunction. Whether FGF21, a liver-derived pro-longevity hormone that is also produced in thymic stroma, including by adipocytes, controls the mechanism of thymic demise is incompletely understood. Here, we demonstrate that elevation of FGF21 in thymic epithelial cells (TECs) and in adipocytes protects against thymic aging,...

Ageing of the cardiovascular system is associated with frailty and various life-threatening diseases. As global populations grow older, age-related conditions increasingly determine healthspan and lifespan. The circulatory system not only supplies nutrients and oxygen to all tissues of the human body and removes by-products but also builds the largest interorgan communication network, thereby serving as a gatekeeper for healthy ageing. Therefore, elucidating organ-specific and cell-specific...

Urea is a primary nitrogen source used as fertilizer in agricultural plant production and a crucial nitrogen metabolite in plants, playing an essential role in modern agriculture. In plants, DUR3 is a proton-driven high-affinity urea transporter located on the plasma membrane. It not only absorbs external low-concentration urea as a nutrient but also facilitates nitrogen transfer by recovering urea from senescent leaves. Despite its importance, the high-affinity urea transport mechanism in...

DNA damage promotes mutations that fuel cancer, ageing and neurodegenerative diseases^(1-3), but surprisingly, the causes and types of damage remain largely unknown. There are three identified mechanisms that damage DNA during transcription: collision of RNA polymerase (RNAP) with the DNA-replication machinery head-on and co-directionally^(4-6), and R-loop-induced DNA breakage^(7-10). Here we identify novel DNA damage reaction intermediates^(11,12) and uncover a fourth transcription-related...

Consequences of age-associated thymic atrophy include declining T-cell responsiveness to pathogens and vaccines and diminished T-cell self-tolerance. Cortical thymic epithelial cells (cTECs) are primary targets of thymic aging, and recent studies suggested that their maintenance requires mTOR signaling downstream of medullary TEC (mTEC)-derived growth factors. Here, to test this hypothesis, we generated a knock-in mouse model in which FGF21 and mCherry are expressed by most mTECs. We find that...

Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock...

CONCLUSIONS: Education plays a crucial role in enabling females to overcome disadvantages associated with the gender paradox in China. Enhancing gender equality in educational opportunities is expected to promote healthy longevity among females in the country.

CONCLUSIONS: Elevated NLR status is associated with increased risk of cognitive impairment in Chinese community-dwelling older adults.

Mosquito-borne flaviviruses, such as dengue virus (DENV), Zika virus (ZIKV), West Nile virus, and yellow fever virus, pose significant public health threats globally. Extensive efforts have led to the development of promising highly active compounds against DENV targeting viral non-structural protein 4B (NS4B) protein. However, due to the cocirculation of flaviviruses and to prepare for emerging flaviviruses, there is a need for more broadly acting antivirals. Host-directed therapy where one...

Osteoporosis and bone injury healing in elderly patients are major medical challenges, often exacerbated by the accumulation of senescent cells. Herein, we show that TPE-Gal, which contains a tetraphenylethene unit and a galactose moiety, offers a promising molecular therapy designed to light up and eliminate senescent cells through a hydrolysis reaction catalyzed by β-galactosidase, an enzyme overexpressed in senescent cells. The reaction produces TPE-OH, which, in turn, increases reactive...