Aging & Longevity
Author Correction: In vivo base editing extends lifespan of a humanized mouse model of prion disease
No abstract
Indoor ventilation frequency and cognitive function among Chinese old adults: the multiple mediation effect of anxiety and self-rated health
CONCLUSIONS: Studies have shown that indoor ventilation frequency can improve cognitive function by reducing anxiety and improving self-rated health in older people Chinese. Encouraging older adults to increase the frequency of indoor ventilation will benefit their mental health and cognitive function.
"Loneliness is a sad disease": oldest old adults' empirical definition of loneliness and social isolation from a mixed-method study in Northern Italy
CONCLUSION: The knowledge of the meanings that oldest old give to the two concepts may inspire advanced intervention aimed at buffering the psychological and social consequences of loneliness and social isolation in the older population.
Establishment and application of a zebrafish model of Werner syndrome identifies sapanisertib as a potential antiaging drug
Aging is a complex process that affects multiple organs, and the discovery of a pharmacological approach to ameliorate aging is considered the Holy Grail of medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish and identified an accelerated aging mutant named meteor (met), harboring a mutation in the Werner syndrome RecQ-like helicase (wrn) gene. Loss of wrn leads to a short lifespan and age-related characteristics in the intestine of zebrafish embryos,...
SIV monoclonal antibody administration spanning treatment interruption in macaques delays viral rebound and selects escape variants
HIV-1 envelope broadly neutralizing antibodies represent a promising component of HIV-1 cure strategies. To evaluate the therapeutic efficacy of combination monoclonal antibodies (mAbs) in a rigorous nonhuman primate model, we tested different combinations of simian immunodeficiency virus (SIV) neutralizing mAbs in SIVmac251-infected rhesus macaques. Antiretroviral therapy-suppressed animals received anti-SIV mAbs targeting multiple Env epitopes spanning analytical treatment interruption (ATI)...
Sex in aging matters: exercise and chronic stress differentially impact females and males across the lifespan
Assessing sex as a biological variable is critical to determining the influence of environmental and lifestyle risks and protective factors mediating behavior and neuroplasticity across the lifespan. We investigated sex differences in affective behavior, memory, and hippocampal neurogenesis following short- or long-term exposure to exercise or chronic mild stress in young and aged mice. Male and female mice were assigned control, running, or chronic stress rearing conditions for 1 month (young)...
Cognitive trajectories and their relationships with education and diets among older adults: a network-based 10-year cohort study
CONCLUSION: Years of education are longitudinally associated with the diet of older adults in the slow cognitive decline group. Food diversity partially mediates the relationship between years of education and cognitive trajectories. Interventions targeting education and dietary behaviors may help alleviate cognitive decline in older adults.
The role of vitamin K2 in cognitive impairment: linking vascular health to brain health
Cognitive impairment, marked by a decline in essential mental aspects such as attention, memory, and problem-solving, is significantly correlated with advancing age. This condition presents a major challenge for the elderly, adversely affecting quality of life, diminishing independence, and imposing substantial burdens on healthcare systems. Recent research indicates that vitamin K2 may be vital for preserving brain health and cognitive function. Traditionally recognized primarily for its role...
The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity
Ubiquitin-conjugating enzymes (E2s) are key for protein turnover and quality control via ubiquitination. Some E2s also physically interact with the proteasome, but it remains undetermined which E2s maintain proteostasis during aging. Here, we find that E2s have diverse roles in handling a model aggregation-prone protein (huntingtin-polyQ) in the Drosophila retina: while some E2s mediate aggregate assembly, UBE2D/effete (eff) and other E2s are required for huntingtin-polyQ degradation. UBE2D/eff...
Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior T cells for cancer immunotherapy
Cellular therapies are living drugs whose efficacy depends on persistence and survival. Expansion of therapeutic T cells employs hypermetabolic culture conditions to promote T cell expansion. We show that typical in vitro expansion conditions generate metabolically and functionally impaired T cells more reliant on aerobic glycolysis than those expanding in vivo. We used dichloroacetate (DCA) to modulate glycolytic metabolism during expansion, resulting in elevated mitochondrial capacity,...
Convergence of orphan quality control pathways at a ubiquitin chain-elongating ligase
Unassembled and partially assembled subunits of multi-protein complexes have emerged as major quality control clients, particularly under conditions of imbalanced gene expression such as stress, aging, and aneuploidy. The factors and mechanisms that eliminate such orphan subunits to maintain protein homeostasis are incompletely defined. Here, we show that the UBR4-KCMF1 ubiquitin ligase complex is required for the efficient degradation of multiple unrelated orphan subunits from the chaperonin,...
Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation
No abstract
The inflammatory profiling in a cohort of older patients suffering from cognitive decline and dementia
CONCLUSIONS: Our data showed similar associations between AD and MD, supporting the concept that late-onset dementia is a complex outcome of aging, intimately linked to the individual's health status as well as frailty.
C-terminal amides mark proteins for degradation via SCF-FBXO31
During normal cellular homeostasis, unfolded and mislocalized proteins are recognized and removed, preventing the build-up of toxic byproducts¹. When protein homeostasis is perturbed during ageing, neurodegeneration or cellular stress, proteins can accumulate several forms of chemical damage through reactive metabolites^(2,3). Such modifications have been proposed to trigger the selective removal of chemically marked proteins^(3-6); however, identifying modifications that are sufficient to...
Integrating single-cell RNA and T cell/B cell receptor sequencing with mass cytometry reveals dynamic trajectories of human peripheral immune cells from birth to old age
A comprehensive understanding of the evolution of the immune landscape in humans across the entire lifespan at single-cell transcriptional and protein levels, during development, maturation and senescence is currently lacking. We recruited a total of 220 healthy volunteers from the Shanghai Pudong Cohort (NCT05206643), spanning 13 age groups from 0 to over 90 years, and profiled their peripheral immune cells through single-cell RNA-sequencing coupled with single T cell and B cell receptor...
Single-cell profiling of the immune landscape across the human lifespan
No abstract
Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells
Somatic stem cell pools comprise diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased hematopoietic stem cells (myHSCs) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but, at the same time, become irreversibly damaged during inflammation and aging. Here we identify an extrinsic factor, semaphorin 4A (Sema4A), which non-cell-autonomously confers myHSC...
Author Correction: Heterochronic parabiosis reprograms the mouse brain transcriptome by shifting aging signatures in multiple cell types
No abstract
PEBP1 amplifies mitochondrial dysfunction-induced integrated stress response
Mitochondrial dysfunction is involved in numerous diseases and the aging process. The integrated stress response (ISR) serves as a critical adaptation mechanism to a variety of stresses, including those originating from mitochondria. By utilizing mass spectrometry-based cellular thermal shift assay (MS-CETSA), we uncovered that phosphatidylethanolamine-binding protein 1 (PEBP1), also known as Raf kinase inhibitory protein (RKIP), is thermally stabilized by stresses which induce mitochondrial...
Raman Spectroscopy in Cellular and Tissue Aging Research
The establishment of various molecular, physiological, and genetic markers for cellular senescence and aging-associated conditions has progressed the aging study. To identify such markers, a combination of optical, proteomic-, and sequencing-based tools is primarily used, often accompanying extrinsic labels. Yet, the tools for clinical detection at the molecular, cellular, and tissue levels are still lacking which profoundly hinders advancements in the specific detection and timely prevention of...
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