Aging & Longevity

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)...

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.

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...

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...

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,...

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,...

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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.

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...

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...

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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...

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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...

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...

Lower episodic memory capability, as seen in development and aging compared with younger adulthood, may partly depend on lower brain network segregation. Here, our objective was twofold: (1) test this hypothesis using within- and between-network functional connectivity (FC) during episodic memory encoding and retrieval, in two independent samples (n = 734, age 7-82 years). (2) Assess associations with age and the ability to predict memory comparing task-general FC and memory-modulated FC. In a...

Fate decisions during immune cell development require temporally precise changes in gene expression. Evidence suggests that the dynamic modulation of these changes is associated with the formation of diverse, membrane-less nucleoprotein assemblies that are termed biomolecular condensates. These condensates are thought to orchestrate fate-determining transcriptional and post-transcriptional processes by locally and transiently concentrating DNA or RNA molecules alongside their regulatory...

High-density lipoprotein (HDL) particle diameter distribution is informative in the diagnosis of many conditions, including Alzheimer's disease (AD). However, obtaining an accurate HDL size measurement is challenging. We demonstrated the utility of measuring the diameter of more than 1,800,000 HDL particles with the deep learning model YOLOv7 (you only look once) from micrographs of 183 HDL samples, including patients with dementia or normal cognition (controls). This method was shown to be more...

Parkinson's disease (PD) is the second most common central neurodegenerative disease in the world after Alzheimer's disease (AD), which mainly occurs in middle-aged and elderly people, and is increasing with the aging of the population. With the increasing incidence of PD, it is particularly important to explore its pathology and provide effective interventions and treatments. The pathogenesis of PD involves a variety of factors such as genetics, environment, and age, and is not yet fully...

Immunity declines with age. This results in a higher risk of age-related diseases, diminished ability to respond to new infections and reduced response to vaccines. The causes of this immune dysfunction are cellular senescence, which occurs in both lymphoid and non-lymphoid tissue, and chronic, low-grade inflammation known as 'inflammageing'. In this Review article, we highlight how the processes of inflammation and senescence drive each other, leading to loss of immune function. To break this...