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α-Synuclein Promotes Atherosclerosis by Impairing Macrophage Autophagic Flux

5 hours 23 minutes ago
Atherosclerosis, recognized as a prototypical age-associated vascular disease, is driven by macrophage foam cell formation. Individuals with Parkinson's disease (PD) exhibit an elevated risk for stroke. While α-synuclein (α-Syn) is known for its neuronal role in PD, its presence in the circulation and potential vascular effects remain unexplored. Here, we identify α-Syn as a previously unrecognized circulating factor that promotes atherosclerosis. α-Syn was detected in human atherosclerotic...
Mengting Qin

uPAR-Targeting T Cell Engager Exerts Senolytic Effects in Mice and Non-Human Primates With Serum Aminotransferase Activity as a Safety Monitor

5 hours 23 minutes ago
Senolytic CAR-T cells targeting uPAR induce dose-dependent toxicities. Although dosage adjustment mitigates these toxicities in laboratory mice, clinical translation remains challenging owing to the unpredictability of CAR-T cell proliferation across heterogeneous patient populations. In contrast, bispecific T-cell engagers (BiTEs) offer a safer alternative with superior dose-titratability. Here, we have developed a GFD-CD3 BiTE by employing the growth factor-like domain (GFD) of the natural...
Jian Deng

Kruppel-like factors regulate lipid homeostasis to modulate SKN-1/Nrf activity, oxidative stress resistance and longevity

5 hours 23 minutes ago
Maintenance of lipid and redox homeostasis is essential for stress resistance and longevity, but the transcriptional networks coordinating these processes remain incompletely understood. In Caenorhabditis elegans, the transcription factors SKN-1A/Nrf1 and SKN-1C/Nrf2 mediate distinct stress responses that promote proteostasis, lipid homeostasis, and oxidative stress resistance. Here, we identify the Krüppel-like factor KLF-1 as a regulator of lipid accumulation that modulates SKN-1 activity....
Jorge Iván Castillo-Quan

Ghrelin Alleviates Aging-Related Cognitive Impairment by Regulating Autophagy-Related Signaling via the SHBG/JNK1/Beclin1 Axis in Microglia

5 hours 23 minutes ago
Cognitive impairment (CI) associated with aging and immunosenescence is linked to metabolic alterations. Microglial senescence and dysregulated autophagy have been implicated as major contributors to this process, but the underlying metabolic regulators remain unclear. This study aimed to identify key metabolic regulators of CI and elucidate their underlying mechanisms. Human cohort analyses, older and D-galactose (D-gal)-induced mouse models, and microglial cell models were integrated to...
Lixing Zhou

Scientists just discovered what coffee really does to your gut and brain

1 day 1 hour ago
A new study suggests coffee may influence mood and brain function by changing the activity of microbes in the gut. Both caffeinated and decaf coffee were linked to lower stress, depression, and impulsivity, while also producing measurable changes in gut bacteria and metabolites. Decaf was associated with better learning and memory, while caffeinated coffee appeared to reduce anxiety and improve attention.

Blood tests reveal why astronauts get constipated in space

1 day 2 hours ago
Spaceflight may dramatically change the gut within weeks, causing bacteria to break down more protein as food moves more slowly through the intestines. The shift could help explain astronaut constipation and may have wider effects on health, making it an important concern for future missions to Mars.

Pomegranate compound improves heart function by up to 80% in study

1 day 4 hours ago
A compound the body can make after eating pomegranates, walnuts, and some berries improved measures of heart function by up to 80% in animal models of a difficult-to-treat form of heart failure. Urolithin A helped stiff heart tissue relax and reduced scarring and abnormal enlargement. It also improved relaxation in engineered human heart tissue.

ALKBH5-mediated microglia-neuron crosstalk inhibits sympathetic innervation and adipocyte browning in male mice

1 day 5 hours ago
Interactions between nervous system and adipose tissue are involved in the regulation of adipocyte browning. However, whether microglial activation participates in the regulation of cold exposure-induced sympathetic innervation and adipocyte browning is unclear. Here, we demonstrate that RNA m6A demethylase ALKBH5 in the microglia nucleus of hypothalamus (PVH) region inhibits cold exposure-induced adipocyte browning in the subcutaneous white adipose tissue (sWAT) of male mice. The single...
Yong-Feng Yang

CD38-activated macrophages drive age-related placental senescence by depleting NAD(+) in decidual stromal cells

1 day 5 hours ago
As delayed childbearing becomes increasingly common, elucidating the mechanisms of age-related placental senescence is critical for the development of effective therapeutic strategies. Here, we integrate metabolomics, single-cell RNA sequencing, and spatial transcriptomics to uncover conserved features of aged placentas in humans, mice, and pigs, namely, increased macrophage CD38 expression and NAD⁺ deficiency. Through pharmacological and genetic approaches, we demonstrate that macrophage CD38...
Lun Hua