Aging & Longevity

A galactose-tethered tetraphenylethene prodrug mediated apoptosis of senescent cells for osteoporosis treatment

5 months 1 week ago
Osteoporosis and bone injury healing in elderly patients are major medical challenges, often exacerbated by the accumulation of senescent cells. Herein, we show that TPE-Gal, which contains a tetraphenylethene unit and a galactose moiety, offers a promising molecular therapy designed to light up and eliminate senescent cells through a hydrolysis reaction catalyzed by β-galactosidase, an enzyme overexpressed in senescent cells. The reaction produces TPE-OH, which, in turn, increases reactive...
Xin Gao

Large-Scale Clustered Transcriptional Silencing Associated With Cellular Senescence

5 months 1 week ago
Senescence is a cell fate associated with age-related pathologies; however, senescence markers are not well-defined. Using single cell multi-isotope imaging mass spectrometry (MIMS), we identified hypercondensed, transcriptionally silent DNA globules in a senescence model induced by dysfunctional telomeres. This architectural phenomenon was associated with geographically clustered transcriptional repression across somatic chromosomes with over-representation of cell cycle genes....
Aditi U Gurkar

Rejuvenating the gut: young plasma therapy improves cell proliferation, IGF-I and IGF-IR expression, and immune defense in aged male rats jejunum

5 months 1 week ago
It is well known that aging affects many systems in the body. The digestive system is one of the systems most affected by aging. In our study, we examined the effects of young plasma treatment on cell proliferation, growth factors, immune defense and histological parameters in the jejunum of aged male rats. For this purpose, aged male Sprague Dawley rats (24 months, n = 7) were treated with pooled plasma (0.5 ml/day, intravenously for 30 days) collected from young (5 weeks, n = 51) rats. Aged...
Ender Deniz Asmaz

Plasma homocysteine level and trajectories in association with longitudinal increase in plasma neurofilament light among urban adults

5 months 1 week ago
We tested whether homocysteine (Hcy) was linked to longitudinal change in plasma neurofilament light chain (NfL) overall and differentially across sex and race in a sample of middle-aged urban adults. We used data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study [n = 690, Age at visit 1 (v(1):2004-2009): 30-66y, 42.1% male, 55.4% African American] to evaluate relationships between NfL levels and both visit 1 Hcy (Hcy(v1)) and time-dependent Hcy...
May A Beydoun

Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST

5 months 1 week ago
Ergothioneine (EGT) is a diet-derived, atypical amino acid that accumulates to high levels in human tissues. Reduced EGT levels have been linked to age-related disorders, including neurodegenerative and cardiovascular diseases, while EGT supplementation is protective in a broad range of disease and aging models. Despite these promising data, the direct and physiologically relevant molecular target of EGT has remained elusive. Here, we use a systematic approach to identify how mitochondria...
Hans-Georg Sprenger

HypoxyStat, a small-molecule form of hypoxia therapy that increases oxygen-hemoglobin affinity

5 months 1 week ago
We have previously demonstrated that chronic inhaled hypoxia is remarkably therapeutic in the premier animal model of mitochondrial Leigh syndrome, the Ndufs4 knockout (KO) mouse. Subsequent work has extended this finding to additional mitochondrial diseases and more common conditions. However, challenges inherent to gas-based therapies have hindered the rapid translation of our findings to the clinic. Here, we tested a small molecule (hereafter termed HypoxyStat) that increases the binding...
Skyler Y Blume

Regulatory Roles of Exosomes in Aging and Aging-Related Diseases

5 months 1 week ago
Exosomes are small vesicles with diameters ranging from 30 to 150 nm. They originate from cellular endocytic systems. These vesicles contain a rich payload of biomolecules, including proteins, nucleic acids, lipids, and metabolic products. Exosomes mediate intercellular communication and are key regulators of a diverse array of biological processes, such as oxidative stress and chronic inflammation. Furthermore, exosomes have been implicated in the pathogenesis of infectious diseases, autoimmune...
Nanyin Xiao

Immune genes involved in synaptic plasticity during early postnatal brain development contribute to post-stroke damage in the aging male rat brain

5 months 1 week ago
Stroke remains a leading cause of mortality and long-term disability worldwide, underscoring the urgent need to identify novel therapeutic targets to enhance brain circuitry repair and functional recovery. This study explores the concept of longevity assurance genes, which primarily function within genetic pathways responsible for repair and maintenance. These pathways encompass molecular and metabolic processes as well as organ- and system-level functions. To investigate this, we employed...
Denisa F V Pirscoveanu

Intact embodiment during perspective-taking in older adults is not affected by focal tDCS

5 months 1 week ago
Embodied processing is crucial for visual perspective taking (VPT), with evidence from non-invasive transcranial direct current stimulation (tDCS) suggesting a causal role of the right temporoparietal junction (rTPJ). However, it is not known whether such embodied factors are maintained in older adults or whether rTPJ-tDCS has comparable effects in advanced age. We employed a balanced and sham-tDCS controlled, double-blinded, cross-over design, including two randomized experimental groups of...
Mandy Roheger

Innovations in aging biology: highlights from the ARDD emerging science & technologies workshop

5 months 1 week ago
The field of biogerontology has established itself through significant lines of research in recent decades. However, despite early breakthroughs, progress in understanding the aging process has been slow. To push the field forward, new methodologies and technologies are likely needed to unravel the complexity of aging. This meeting brought together leading scientists and innovators to explore some emerging approaches, presenting groundbreaking advancements in four key sessions, culminating in a...
Maximilian Unfried

ImmuneLENS characterizes systemic immune dysregulation in aging and cancer

5 months 1 week ago
Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with...
Robert Bentham

Exploring morphological and microstructural signatures across the Alzheimer's spectrum and risk factors

5 months 2 weeks ago
Neural alterations, including myelin degeneration and inflammation-related iron burden, may accompany early Alzheimer's disease (AD) pathophysiology. This study aims to identify multi-modal signatures associated with MRI-derived atrophy and quantitative MRI (qMRI) measures of myelin and iron in a unique dataset of 158 participants across the AD spectrum, including those without cognitive impairment, at familial risk for AD, with mild cognitive impairment, and with AD dementia. Our results...
Aurélie Bussy

Cell enlargement modulated by GATA4 and YAP instructs the senescence-associated secretory phenotype

5 months 2 weeks ago
Dynamic changes in cell size are associated with development and pathological conditions, including aging. Although cell enlargement is a prominent morphological feature of cellular senescence, its functional implications are unknown; moreover, how senescent cells maintain their enlargement state is less understood. Here we show that an extensive remodeling of actin cytoskeleton is necessary for establishing senescence-associated cell enlargement and pro-inflammatory senescence-associated...
Joae Joung

BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress

5 months 2 weeks ago
In contrast to mammals, adult zebrafish achieve complete heart regeneration via proliferation of cardiomyocytes. Surprisingly, we found that regenerating cardiomyocytes experience DNA replication stress, which represents one reason for declining tissue regeneration during aging in mammals. Pharmacological inhibition of ATM and ATR kinases revealed that DNA damage response signaling is essential for zebrafish heart regeneration. Manipulation of Bone Morphogenetic Protein (BMP)-Smad signaling...
Mohankrishna Dalvoy Vasudevarao
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