Aging & Longevity
Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice
The prevalent itching condition associated with aging, historically referred to as senile pruritus, diminishes quality of life. Despite its impact, effective treatments remain elusive, largely due to an incomplete understanding of its pathological cause. In this study, we reveal a subset of dorsal root ganglion neurons enriched with Zn2+ that express the vesicular Zn2+ transporter TMEM163. These neurons form direct synapses with and modulate the activity of spinal NPY+ inhibitory interneurons....
Sexually dimorphic differences in angiogenesis markers are associated with brain aging trajectories in humans
Aberrant angiogenesis could contribute to the development of cognitive impairment and represent a therapeutic target for preventing dementia. However, most studies addressing angiogenesis and cognitive impairment focus on model organisms. To test the relevance of angiogenesis to human cognitive aging, we evaluated associations of circulating blood markers of angiogenesis with brain aging trajectories in a pooled two-center sample from deeply phenotyped longitudinal human cohorts (n = 435; female...
Plasma triacylglycerol length and saturation level mark healthy aging groups in humans
Complex lipids, essential components in biological processes, exhibit conserved age-related changes that alter membrane properties and cellular functions and are implicated as biomarkers and contributors to longevity and age-related diseases. While physical activity alleviates age-related comorbidities and physical impairments, comprehensive exploration of the underlying biological mechanisms, particularly at the level of complex lipids, remains limited. However, clinical studies suggest that...
Slowed epigenetic aging in Olympic champions compared to non-champions
The lifestyle patterns of top athletes are highly disciplined, featuring strict exercise regimens, nutrition plans, and mental preparation, often beginning at a young age. Recently, it was shown that physically active individuals exhibit slowed epigenetic aging and better age-related outcomes. Here, we investigate whether the extreme intensity of physical activity of Olympic champions still has a beneficial effect on epigenetic aging. To test this hypothesis, we examined the epigenetic aging of...
Use of Medications With Somnolence Adverse Effects and Somnolence Symptoms Among Older Adults in the U.S
OBJECTIVES: Nearly half of older adults experience somnolence, but the link between medications with somnolence as an adverse effect and somnolence is unclear. This study investigated the association between polypharmacy and somnolence symptoms (excessive sleepiness or long sleep duration).
Expression of alpha smooth muscle actin decreases with ageing and increases upon lumen obstruction in mouse brain pericytes
Cerebral pericytes are mural cells covering brain microvessels, organized as ensheathing, mesh and thin-strand pericytes. These latter two, together called capillary pericytes, have low levels of alpha smooth muscle actin (α-SMA), regulating basal vascular tone and applying a slow influence on cerebral blood flow. Pericytes are subject to alterations in ageing which may be even more pronounced in age-related pathologies, including microinfarcts, which usually affect a large number of vessels in...
Decoding senescence of aging single cells at the nexus of biomaterials, microfluidics, and spatial omics
Aging has profound effects on the body, most notably an increase in the prevalence of several diseases. An important aging hallmark is the presence of senescent cells that no longer multiply nor die off properly. Another characteristic is an altered immune system that fails to properly self-surveil. In this multi-player aging process, cellular senescence induces a change in the secretory phenotype, known as senescence-associated secretory phenotype (SASP), of many cells with the intention of...
Noninvasive rejuvenation strategy of nickel-rich layered positive electrode for Li-ion battery through magneto-electrochemical synergistic activation
Nickel-rich layered oxides are one of the most promising positive electrode active materials for high-energy Li-ion batteries. Unfortunately, the practical performance is inevitably circumscribed by the structural deterioration deriving from the Ni/Li antisite disorder, leading to severe capacity loss and life attenuation. Herein, we propose an economical and facile rejuvenation strategy by employing the magneto-electrochemical synergistic activation targeting the positive electrode in assembled...
Quantitative determination of the spatial distribution of components in single cells with CellDetail
The distribution of biomolecules within cells changes upon aging and diseases. To quantitatively determine the spatial distribution of components inside cells, we built the user-friendly open-source 3D-cell-image analysis platform Cell Detection and Analysis of Intensity Lounge (CellDetail). The algorithm within CellDetail is based on the concept of the dipole moment. CellDetail provides quantitative values for the distribution of the polarity proteins Cdc42 and Tubulin in young and aged...
Age-related decline in CD8<sup>+</sup> tissue resident memory T cells compromises antitumor immunity
Aging compromises antitumor immunity, but the underlying mechanisms remain elusive. Here, we report that aging impairs the generation of CD8^(+) tissue resident memory T (T(RM)) cells in nonlymphoid tissues in mice, thus compromising the antitumor activity of aged CD8^(+) T cells, which we also observed in human lung adenocarcinoma. We further identified that the apoptosis regulator BFAR was highly enriched in aged CD8^(+) T cells, in which BFAR suppressed cytokine-induced JAK2 signaling by...
Inhibition of zDHHC7-driven protein S-palmitoylation prevents cognitive deficits in an experimental model of Alzheimer's disease
Protein post-translational modifications (PTM) play a crucial role in the modulation of synaptic function and their alterations are involved in the onset and progression of neurodegenerative disorders. S-palmitoylation is a PTM catalyzed by zinc finger DHHC domain containing (zDHHC) S-acyltransferases that affects both localization and activity of proteins regulating synaptic plasticity and amyloid-β (Aβ) metabolism. Here, we found significant increases of both zDHHC7 expression and protein...
Using the phenotype differences model to identify genetic effects in samples of partially genotyped sibling pairs
The identification of causal relationships between specific genes and social, behavioral, and health outcomes is challenging due to environmental confounding from population stratification and dynastic genetic effects. Existing methods to eliminate environmental confounding leverage random genetic variation resulting from recombination and require within-family dyadic genetic data (i.e., parent-child and/or sibling pairs), meaning they can only be applied in relatively small and selected...
Coordination between the eIF2 kinase GCN2 and p53 signaling supports purine metabolism and the progression of prostate cancer
Cancers invoke various pathways to mitigate external and internal stresses to continue their growth and progression. We previously reported that the eIF2 kinase GCN2 and the integrated stress response are constitutively active in prostate cancer (PCa) and are required to maintain amino acid homeostasis needed to fuel tumor growth. However, although loss of GCN2 function reduces intracellular amino acid availability and PCa growth, there is no appreciable cell death. Here, we discovered that the...
Educational Disparities in Preventable Deaths: Do They Explain the Longevity Gap Between Mexico and Spain?
OBJECTIVE: Determine how preventable causes of death contribute to the life expectancy gap between Mexico and Spain.
A mortality timer based on nucleolar size triggers nucleolar integrity loss and catastrophic genomic instability
Genome instability is a hallmark of aging, with the highly repetitive ribosomal DNA (rDNA) within the nucleolus being particularly prone to genome instability. Nucleolar enlargement accompanies aging in organisms ranging from yeast to mammals, and treatment with many antiaging interventions results in small nucleoli. Here, we report that an engineered system to reduce nucleolar size robustly extends budding yeast replicative lifespan in a manner independent of protein synthesis rate or rDNA...
Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer
Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. In this study, we investigated how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single-cell resolution, yielding a comprehensive resource for aging and cancer biology. Aged epithelial cells exhibit epigenetic and transcriptional changes in metabolic, pro-inflammatory and cancer-associated genes. Aged stromal cells...
Asparagine prevents intestinal stem cell aging via the autophagy-lysosomal pathway
The age-associated decline in intestinal stem cell (ISC) function is a key factor in intestinal aging in organisms, resulting in impaired intestinal function and increased susceptibility to age-related diseases. Consequently, it is imperative to develop effective therapeutic strategies to prevent ISC aging and functional decline. In this study, we utilized an aging Drosophila model screening of amino acids and found that asparagine (Asn), a nonessential amino acid in vivo, exhibits its profound...
Leveraging research into sex differences and steroid hormones to improve brain health
Sex differences, driven in part by steroid hormones, shape the structure and function of the brain throughout the lifespan and manifest across brain health and disease. The influence of steroid hormones on neuroplasticity, particularly in the adult hippocampus, differs between the sexes, which has important implications for disorders and diseases that compromise hippocampus integrity, such as depression and Alzheimer disease. This Review outlines the intricate relationship between steroid...
Views of aging and subjective cognition in middle-aged and older adults: A systematic review
CONCLUSION: Most studies supported associations between views of aging and subjective cognition. More longitudinal as well as qualitative research is needed to advance understanding of factors that influence these relationships.
Does the digital divide accelerate cognitive function decline related to the poor management of diabetes in later life?
INTRODUCTION: The objective is to investigate the role of digital exclusion in the association between diabetes and cognitive function among adults aged 50 and above.
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