A subset of human dermal fibroblasts overexpressing Cockayne syndrome group B protein resist UVB radiation-mediated premature senescence.

Ultraviolet B (UVB) radiation is a major contributor to skin photoaging. Although mainly absorbed by the epidermis, UVB photons managing to penetrate the upper dermis affect human dermal fibroblasts (HDFs), leading, among others, to the accumulation of senescent cells. In vitro studies have shown that repeated exposures to subcytotoxic UVB radiation doses provoke HDFs' premature senescence shortly after the end of the treatment period.

Age-Dependent Bi-Phasic Dynamics of Ly49CD8 Regulatory T Cell Population.

Aging is tightly associated with reduced immune protection but increased risk of autoimmunity and inflammatory conditions. Regulatory T cells are one of the key cells to maintaining immune homeostasis. The age-dependent changes in CD4Foxp3 regulatory T cells (Tregs) have been well documented.

Multi-omic analysis of biological aging biomarkers in long-term calorie restriction and endurance exercise practitioners: A cross-sectional study.

Calorie restriction (CR) and physical exercise (EX) are well-established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long-term follow-up.

Role of PI3K/AKT/MAOA in glucocorticoid-induced oxidative stress and associated premature senescence of the trabecular meshwork.

The oxidative stress-induced premature senescence of trabecular meshwork (TM) represents a pivotal risk factor for the development of glucocorticoid-induced glaucoma (GIG). This study aimed to elucidate the pathogenesis of TM senescence in GIG. MethodsIntraocular pressure (IOP), transmission electron microscopy and senescence-associated protein expression in TM were evaluated in GIG mice.

Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny.

The mitochondrial genome (mtDNA) is an important source of inherited extranuclear variation. Clonal increases in mtDNA mutation heteroplasmy have been implicated in aging and disease, although the impact of this shift on cell function is challenging to assess. Reprogramming to pluripotency affects mtDNA mutation heteroplasmy.

Age-associated accumulation of RAB9 disrupts oocyte meiosis.

The critical role of some RAB family members in oocyte meiosis has been extensively studied, but their role in oocyte aging remains poorly understood. Here, we report that the vesicle trafficking regulator, RAB9 GTPase, is essential for oocyte meiosis and aging in humans and mice. RAB9 was mainly located at the meiotic spindle periphery and cortex during oocyte meiosis.

Organellar quality control crosstalk in aging-related disease: Innovation to pave the way.

Organellar homeostasis and crosstalks within a cell have emerged as essential regulatory and determining factors for the survival and functions of cells. In response to various stimuli, cells can activate the organellar quality control systems (QCS) to maintain homeostasis. Numerous studies have demonstrated that dysfunction of QCS can lead to various aging-related diseases such as neurodegenerative, pulmonary, cardiometabolic diseases and cancers.

Associations of combined accelerated biological aging and genetic susceptibility with incidence of heart failure in a population-based cohort study.

The global aging population raises concerns about heart failure (HF), yet its association with accelerated biological age (BA) remains inadequately understood. We aimed to examine the longitudinal association between BA acceleration and incident HF risk, assess its modifying effect on genetic susceptibility, and how much BA acceleration mediates the impact of modifiable health behaviors on incident HF. We analyzed 274,608 UK Biobank participants without HF at baseline.

Telomerase reverse transcriptase gene knock-in unleashes enhanced longevity and accelerated damage repair in mice.

While previous research has demonstrated the therapeutic efficacy of telomerase reverse transcriptase (TERT) overexpression using adeno-associated virus and cytomegalovirus vectors to combat aging, the broader implications of TERT germline gene editing on the mammalian genome, proteomic composition, phenotypes, lifespan extension, and damage repair remain largely unexplored. In this study, we elucidate the functional properties of transgenic mice carrying the Tert transgene, guided by precise gene targeting into the Rosa26 locus via embryonic stem (ES) cells under the control of the elongation factor 1α (EF1α) promoter. The Tert knock-in (TertKI) mice harboring the EF1α-Tert gene displayed elevated telomerase activity, elongated telomeres, and extended lifespan, with no spontaneous genotoxicity or carcinogenicity.

Estradiol deficiency as a consequence of aging contributes to the depletion of the satellite cell pool in female mice.

The effects of aging on the satellite cell pool have primarily been studied in male mice, where the role of cell-intrinsic versus environmental changes on satellite cell function remains contentious. Estradiol is necessary for maintenance of satellite cell pool size in adult female mice-here we investigate the hypothesis that in females, estradiol is a major environmental driver of age-associated effects on satellite cells. In 24-26 month-old ovarian senescent mice, we find the satellite cell pool size is severely diminished in certain muscles (TA and EDL) but only marginally affected in others (soleus and gastrocnemius).

Phenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity.

Centenarians and their relatives possess a notable survival advantage, with higher longevity and reduced susceptibility to major age-related diseases. To date, characteristic omics profiles of centenarians have been described, demonstrating that these individuals with exceptional longevity regulate their metabolism to adapt and incorporate more resilient biomolecules into their cells. Among these adaptations, the lipidomic profile stands out.

Skeletal muscle mitochondrial fragmentation predicts age-associated decline in physical capacity.

Ageing substantially impairs skeletal muscle metabolic and physical function. Skeletal muscle mitochondrial health is also impaired with ageing, but the role of skeletal muscle mitochondrial fragmentation in age-related functional decline remains imprecisely characterized. Here, using a cross-sectional study design, we performed a detailed comparison of skeletal muscle mitochondrial characteristics in relation to in vivo markers of exercise capacity between young and middle-aged individuals.

Gut microbiota metabolism of branched-chain amino acids and their metabolites can improve the physiological function of aging mice.

The metabolism of branched-chain amino acids by gut microbiota can improve overall health and may reverse aging. In this study, we investigated Parabacteroides merdae, a gut microbe that is known to catabolise branched-chain amino acids (BCAAs). Three metabolites of BCAAs isovalerate, 2-methylbutyrate, and isobutyrate were used to treat D-gal induced aging mice.

The ultrastructural and proteomic analysis of mitochondria-associated endoplasmic reticulum membrane in the midbrain of a Parkinson's disease mouse model.

Recent studies indicated that the dysregulation of mitochondria-associated endoplasmic reticulum membrane (MAM) could be a significant hub in the pathogenesis of Parkinson's disease (PD). However, little has been known about how MAM altered in PD. This study was aimed to observe morphological changes and analyze proteomic profiles of MAM in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models.

Piezo1 exacerbates inflammation-induced cartilaginous endplate degeneration by activating mitochondrial fission via the Ca/CaMKII/Drp1 axis.

Mitochondrial homeostasis plays a crucial role in degenerative joint diseases, including cartilaginous endplate (CEP) degeneration. To date, research into mitochondrial dynamics in IVDD is at an early stage. Since Piezo1 is a novel Ca-permeable channel, we asked whether Piezo1 could modulate mitochondrial fission through Ca signalling during CEP degeneration.

Knockdown of RUVBL2 improves hnRNPA2/B1-stress granules dynamics to inhibit perioperative neurocognitive disorders in aged mild cognitive impairment rats.

Perioperative neurocognitive disorders (PND) is common in aged mild cognitive impairment (MCI) patients and can accelerate the progression to dementia. This process involves heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1)-mediated aggregates of stress granules (SGs), while RUVBL2 influences the dynamics of these SGs. Our research explored a new target for modulating hnRNAPA2/B1-SGs dynamics to accelerate their disassembly and potentially delay MCI progression due to PND.

Overlooked histories in ageing research: Pioneering women at the foundation of our field.

A list of this decade's most prominent names in ageing research would undoubtedly include many women who have led the field in recent years. While the field, and science in general, still have far to go in achieving gender parity in opportunities and recognition, we can celebrate the progress made to date. However, the longer 'history of the field' that many of us present in our classrooms, conference halls and writings often tends to be dominated by men.

Epigenetic age acceleration predicts subject-specific white matter degeneration in the human brain.

Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. A specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individual's brain affected by their unique white matter hyperintensity location and volume.