Aging & Longevity

Neuronal microstructural changes in the human brain are associated with neurocognitive aging

4 weeks 1 day ago
Gray matter (GM) alterations play a role in aging-related disorders like Alzheimer's disease and related dementias, yet MRI studies mainly focus on macroscopic changes. Although reliable indicators of atrophy, morphological metrics like cortical thickness lack the sensitivity to detect early changes preceding visible atrophy. Our study aimed at exploring the potential of diffusion MRI in unveiling sensitive markers of cortical and subcortical age-related microstructural changes and assessing...
Kavita Singh

Association between epigenetic age and type 2 diabetes mellitus or glycemic traits: A longitudinal twin study

4 weeks 1 day ago
Epigenetic clocks based on DNA methylation have been known as biomarkers of aging, including principal component (PC) clocks representing the degree of aging and DunedinPACE representing the pace of aging. Prior studies have shown the associations between epigenetic aging and T2DM, but the results vary by epigenetic age metrics and people. This study explored the associations between epigenetic age metrics and T2DM or glycemic traits, based on 1070 twins (535 twin pairs) from the Chinese...
Ke Miao

Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK

1 month ago
The accumulation of lipid droplets (LDs) in aging and Alzheimer's disease brains is considered a pathological phenomenon with unresolved cellular and molecular mechanisms. Utilizing stimulated Raman scattering (SRS) microscopy, we observed significant in situ LD accumulation in microglia of tauopathy mouse brains. SRS imaging, combined with deuterium oxide (D(2)O) labeling, revealed heightened lipogenesis and impaired lipid turnover within LDs in tauopathy fly brains and human neurons derived...
Yajuan Li

Single-cell analysis reveals context-dependent, cell-level selection of mtDNA

1 month ago
Heteroplasmy occurs when wild-type and mutant mitochondrial DNA (mtDNA) molecules co-exist in single cells¹. Heteroplasmy levels change dynamically in development, disease and ageing^(2,3), but it is unclear whether these shifts are caused by selection or drift, and whether they occur at the level of cells or intracellularly. Here we investigate heteroplasmy dynamics in dividing cells by combining precise mtDNA base editing (DdCBE)⁴ with a new method, SCI-LITE (single-cell combinatorial indexing...
Anna V Kotrys

High clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue

1 month ago
Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: 'pseudo-diploid' cells harboring few SCNAs and highly...
Ning Zhang

Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo

1 month ago
Three-dimensional organoid culture technologies have revolutionized cancer research by allowing for more realistic and scalable reproductions of both tumour and microenvironmental structures^(1-3). This has enabled better modelling of low-complexity cancer cell behaviours that occur over relatively short periods of time⁴. However, available organoid systems do not capture the intricate evolutionary process of cancer development in terms of tissue architecture, cell diversity, homeostasis and...
L Francisco Lorenzo-Martín

Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina

1 month ago
Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated...
Yidan Liu

Elimination of subtelomeric repeat sequences exerts little effect on telomere essential functions in <em>Saccharomyces cerevisiae</em>

1 month ago
Telomeres, which are chromosomal end structures, play a crucial role in maintaining genome stability and integrity in eukaryotes. In the baker's yeast Saccharomyces cerevisiae, the X- and Y'-elements are subtelomeric repetitive sequences found in all 32 and 17 telomeres, respectively. While the Y'-elements serve as a backup for telomere functions in cells lacking telomerase, the function of the X-elements remains unclear. This study utilized the S. cerevisiae strain SY12, which has three...
Can Hu

The senescence-associated secretory phenotype and its physiological and pathological implications

1 month ago
Cellular senescence is a state of terminal growth arrest associated with the upregulation of different cell cycle inhibitors, mainly p16 and p21, structural and metabolic alterations, chronic DNA damage responses, and a hypersecretory state known as the senescence-associated secretory phenotype (SASP). The SASP is the major mediator of the paracrine effects of senescent cells in their tissue microenvironment and of various local and systemic biological functions. In this Review, we discuss the...
Boshi Wang

Downregulation of PLIN2 in human dermal fibroblasts impairs mitochondrial function in an age-dependent fashion and induces cell senescence via GDF15

1 month ago
Perilipin 2 (PLIN2) is a lipid droplet (LD)-coating protein playing important roles in lipid homeostasis and suppression of lipotoxicity in different tissues and cell types. Recently, a role for PLIN2 in supporting mitochondrial function has emerged. PLIN2 dysregulation is involved in many metabolic disorders and age-related diseases. However, the exact consequences of PLIN2 dysregulation are not yet completely understood. In this study, we knocked down (KD) PLIN2 in primary human dermal...
Antonio Chiariello

The impact of the senescent microenvironment on tumorigenesis: Insights for cancer therapy

1 month ago
The growing global burden of cancer, especially among people aged 60 years and over, has become a key public health issue. This trend suggests the need for a deeper understanding of the various cancer types in order to develop universally effective treatments. A prospective area of research involves elucidating the interplay between the senescent microenvironment and tumor genesis. Currently, most oncology research focuses on adulthood and tends to ignore the potential role of senescent...
Wenqiang Zhang

Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence

1 month ago
Increasing evidence indicates that terminally differentiated neurons in the brain may recommit to a cell cycle-like process during neuronal aging and under disease conditions. Because of the rare existence and random localization of these cells in the brain, their molecular profiles and disease-specific heterogeneities remain unclear. Through a bioinformatics approach that allows integrated analyses of multiple single-nucleus transcriptome datasets from human brain samples, these rare cell...
Deng Wu

Comprehensive profiling of L1 retrotransposons in mouse

1 month ago
L1 elements are retrotransposons currently active in mammals. Although L1s are typically silenced in most normal tissues, elevated L1 expression is associated with a variety of conditions, including cancer, aging, infertility and neurological disease. These associations have raised interest in the mapping of human endogenous de novo L1 insertions, and a variety of methods have been developed for this purpose. Adapting these methods to mouse genomes would allow us to monitor endogenous in vivo L1...
Xuanming Zhang

Antipsychotic-induced epigenomic reorganization in frontal cortex of individuals with schizophrenia

1 month ago
Genome-wide association studies have revealed >270 loci associated with schizophrenia risk, yet these genetic factors do not seem to be sufficient to fully explain the molecular determinants behind this psychiatric condition. Epigenetic marks such as post-translational histone modifications remain largely plastic during development and adulthood, allowing a dynamic impact of environmental factors, including antipsychotic medications, on access to genes and regulatory elements. However, few...
Bohan Zhu

Evolutionarily conserved neural responses to affective touch in monkeys transcend consciousness and change with age

1 month ago
Affective touch-a slow, gentle, and pleasant form of touch-activates a different neural network than which is activated during discriminative touch in humans. Affective touch perception is enabled by specialized low-threshold mechanoreceptors in the skin with unmyelinated fibers called C tactile (CT) afferents. These CT afferents are conserved across mammalian species, including macaque monkeys. However, it is unknown whether the neural representation of affective touch is the same across...
Joey A Charbonneau

Changes in well-being among socially isolated older people during the COVID-19 pandemic: An outcome-wide analysis

1 month ago
Older adults experienced major changes during the COVID-19 pandemic and ensuing restrictions, and it might be expected that those who were already socially isolated before the pandemic were particularly vulnerable. We apply an outcome-wide longitudinal design on 4,636 participants (mean age 66.8 y) from the English Longitudinal Study of Ageing, observed in 2018/19 and early (June/July 2020) and later (November/December 2020) in the pandemic. Social isolation is defined using an index including...
Claryn S J Kung

Exacerbated atherosclerosis in progeria is prevented by progerin elimination in vascular smooth muscle cells but not endothelial cells

1 month ago
Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by the expression of progerin, a mutant protein that accelerates aging and precipitates death. Given that atherosclerosis complications are the main cause of death in progeria, here, we investigated whether progerin-induced atherosclerosis is prevented in HGPSrev-Cdh5-CreERT2 and HGPSrev-SM22α-Cre mice with progerin suppression in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), respectively....
Ignacio Benedicto

Multimodal cell atlas of the ageing human skeletal muscle

1 month ago
Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people¹. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing². Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples^(3,4). Here we...
Yiwei Lai

Targeting dysregulated phago-/auto-lysosomes in Sertoli cells to ameliorate late-onset hypogonadism

1 month ago
Age-related changes in testicular function can impact health and well-being. The mechanisms underlying age-related testicular dysfunction, such as late-onset hypogonadism (LOH), remain incompletely understood. Using single-cell RNA sequencing on human testes with LOH, we delineated Sertoli cells (SCs) as pivotal metabolic coordinators within the testicular microenvironment. In particular, lysosomal acidity probing revealed compromised degradative capacity in aged SCs, hindering autophagy and...
Zhiwen Deng
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