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1 month 2 weeks ago
Science, Volume 387, Issue 6736, Page 807-807, February 2025.

H. Holden Thorp

Longitudinal analysis of a dominantly inherited Alzheimer disease mutation carrier protected from dementia

1 month 2 weeks ago
We conducted an in-depth longitudinal study on an individual carrying the presenilin 2 p.Asn141Ile mutation, traditionally associated with dominantly inherited Alzheimer's disease (AD), who has remarkably remained asymptomatic past the expected age of clinical onset. This study combines genetic, neuroimaging and biomarker analyses to explore the underpinnings of this resilience. Unlike typical progression in dominantly inherited AD, tau pathology in this case was confined to the occipital region...
Jorge J Llibre-Guerra

Phospho-tau serine-262 and serine-356 as biomarkers of pre-tangle soluble tau assemblies in Alzheimer's disease

1 month 2 weeks ago
Patients with Alzheimer's disease (AD) with little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those with advanced NFTs. The formation of NFTs can be prevented by targeting the intermediate soluble tau assemblies (STAs). However, biochemical understanding and biomarkers of STAs are lacking. We show that Tris-buffered saline-soluble tau aggregates from autopsy-verified AD brain tissues include the core...
Tohidul Islam

Senescence as a molecular target in skin aging and disease

1 month 2 weeks ago
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...
Henriette Thau

Self-optimized contact in air-robust thermoelectric junction towards long-lasting heat harvesting

1 month 2 weeks ago
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...
Airan Li

Pharmacological CDK4/6 inhibition promotes vulnerability to lysosomotropic agents in breast cancer

1 month 2 weeks ago
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,...
Jamil Nehme

Impact of Mlkl or Ripk3 deletion on age-associated liver inflammation, metabolic health, and lifespan

1 month 2 weeks ago
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...
Sabira Mohammed

Unraveling the link between frailty and Alzheimer's disease biomarkers in patients with mild cognitive impairment

1 month 2 weeks ago
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...
Simona Buscarnera

Active aging education: an effective tool for enhancing knowledge and attitudes of health volunteers: a clinical trial study

1 month 2 weeks ago
CONCLUSION: Trained volunteers can effectively convey critical health and cultural messages, make informed decisions, and enhance the local population's access to primary healthcare. The results of this study demonstrate that the active aging educational intervention improved the knowledge and attitudes of health volunteers. Therefore, leveraging the potential of health volunteers to teach active aging can improve the health and well-being of the elderly population.
Fatemeh Asgharian

Astrocytic EphA4 signaling is important for the elimination of excitatory synapses in Alzheimer's disease

1 month 2 weeks ago
Cell surface receptors, including erythropoietin-producing hepatocellular A4 (EphA4), are important in regulating hippocampal synapse loss, which is the key driver of memory decline in Alzheimer's disease (AD). However, the cell-specific roles and mechanisms of EphA4 are unclear. Here, we show that EphA4 expression is elevated in hippocampal CA1 astrocytes in AD conditions. Specific knockout of astrocytic EphA4 ameliorates excitatory synapse loss in the hippocampus in AD transgenic mouse models....
Xin Yang

Maturation and detoxification of synphilin-1 inclusion bodies regulated by sphingolipids

1 month 2 weeks ago
Due to proteostasis stress induced by aging or disease, misfolded proteins can form toxic intermediate species of aggregates and eventually mature into less toxic inclusion bodies (IBs). Here, using a yeast imaging-based screen, we identified 84 potential synphilin-1 (SY1) IB regulators and isolated the conserved sphingolipid metabolic components in the most enriched groups. Furthermore, we show that, in both yeast cells and mammalian cells, SY1 IBs are associated with mitochondria....
Xiuling Cao

The role of protective genetic variants in modulating epigenetic aging

1 month 2 weeks ago
Several progeroid syndromes' causative mutations have been linked to epigenetic age acceleration as measured via several epigenetic clocks. At the same time, several protective variants have also been discovered that can reduce the risk of developing certain age-related disorders. However, the impact of these protective variants on epigenetic aging has not been well elucidated. Our research, which involved screening over 14,669 healthy individuals enrolled in the Qatar BioBank (QBB) and...
Yosra Bejaoui

Longevity Humans Have Youthful Erythrocyte Function and Metabolic Signatures

1 month 2 weeks ago
Longevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging-related diseases. It has long been speculated that "rejuvenation molecules" exist in their blood to promote extended lifespan. We unexpectedly discovered that longevity individuals exhibit erythrocyte oxygen release function similar to young individuals, whereas most elderly show reduced oxygen release capacity. Untargeted erythrocyte metabolomics profiling revealed that longevity...
Fang Yu