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In first human test, genetically modified pancreas cells injected into patient’s arm evade immune attack, produce insulin

Discovery of a bacterium could reveal more about massive die-off, perhaps aid recovery

Parkinson's Disease (PD) is an incurable neurodegenerative disease that causes movement disorders. Neurons in PD aggregate α-synuclein and are depleted from the substantia nigra (SN), which is a movement control hub. The presence of α-synuclein-reactive T cells in PD patient blood suggests a role for adaptive immunity in the pathogenesis of PD. However, the characteristics of this response within the brain are not well understood. Here, we employed single-nucleus RNAseq, spatial transcriptomics,...

Caloric restriction slows or prevents Alzheimer's disease in animal models. Calorie restriction is typically implemented in rodents through feeding once per day; as the animals quickly consume their food, they are subject to a prolonged self-imposed fasting period between meals. Here, we examine the distinct contributions of fasting and reduced calories to the beneficial effects of calorie restriction on Alzheimer's disease by placing male and female 3xTg and non-transgenic control mice on a...

The expression levels of telomerase exhibit regulatory heterogeneity across different cell types and various biological stages of cell development. The expression of telomerase is dynamically regulated across cell types and developmental stages, with its activity predominantly determined by the abundance of its catalytic subunit, telomerase reverse transcriptase (TERT). Telomerase levels are typically high in the pluripotent embryonic stem cells, germline cells, and cancer cells, and silenced in...

Lysosomes are membranous organelles that are crucial for cell function and organ physiology. Serving as the terminal stations of the endocytic pathway, lysosomes have fundamental roles in the degradation of endogenous and exogenous macromolecules and particles as well as damaged or superfluous organelles. Moreover, the lysosomal membrane is a docking and activation platform for several signalling components, including mTOR complex 1 (mTORC1), which orchestrates metabolic signalling in the cell....

Frailty is a multifaceted clinical state associated with accelerated aging and adverse health outcomes. Informed etiological models of frailty hold promise for producing widespread health improvements across the aging population. Frailty is currently measured using aggregate scores, which obscure etiological pathways that are only relevant to subcomponents of frailty. Here we perform a multivariate genome-wide association study of the latent genetic architecture between 30 frailty deficits,...

CONCLUSIONS: SARA-OBS results contribute to defining subgroups of older adults at risk of functional decline over 6 months, specifically subjects with SPPB = 8, affecting GS and the 6MWD. Additionally, the SO subpopulation exhibited a relevant deterioration in physical function as evaluated by the 6MWD.

Ribosome-associated quality control (RQC) is a pivotal biological process that governs the fidelity of messenger RNA (mRNA) homeostasis and protein synthesis. Defects in RQC are implicated in cellular dysfunction and proteotoxicity, but their impact on aging remains elusive. Here, we show that Pelota, the ribosome rescue factor, promotes longevity and protects against age-related pathological phenotypes in multiple metazoan species. By performing a targeted genetic screen, we find that Pelota is...

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The degradation of cellular components through autophagy is essential for longevity and healthy aging. However, autophagy function decreases with aging, contributing to age-related diseases. In this study, we characterized a small-molecule activator of autophagy called AA-20 that enhances autophagy and lipid droplet clearance in human cells and in the nematode Caenorhabditis elegans. AA-20 reduces polyglutamine aggregation in an autophagy-dependent manner in both human cells and C. elegans,...

Ribosome-associated quality control (RQC) is a pivotal biological process that governs the fidelity of messenger RNA (mRNA) homeostasis and protein synthesis. Defects in RQC are implicated in cellular dysfunction and proteotoxicity, but their impact on aging remains elusive. Here, we show that Pelota, the ribosome rescue factor, promotes longevity and protects against age-related pathological phenotypes in multiple metazoan species. By performing a targeted genetic screen, we find that Pelota is...

Gut microbial stability typically decreases with physiological aging. This decline may vary between sexes and can potentially be mitigated by adopting a healthy lifestyle. Microbial guilds, defined as functionally coherent groups of bacteria, may serve as meaningful ecological indicators of aging. This study included 2944 participants aged 51-89 years from the Shanghai Men's and Women's Health Studies. Using 16S rRNA gene sequencing and a guild-based approach, we evaluated the associations...

Tissue-resident memory T (T(RM)) cells are a specialised subset of immune cells that remain within tissues, playing a vital role in localised immune defence and long-term immunity. Unlike circulating memory T cells, T(RM) cells do not recirculate to provide rapid and effective responses against previously encountered pathogens at the tissue level. The formation of T(RM) cells is driven by tissue-specific cues, guiding their differentiation and retention within organs such as the skin, lungs and...