Aging & Longevity
Enhancer Rewiring Orchestrates Inflammation and Loss of Cell Identity During Muscle Stem Cell Aging
Loss of regeneration is a key feature of aging organs, often linked to stem cell exhaustion. Skeletal muscle stem cells (MuSCs) undergo age-related numerical and functional decline, contributing to reduced regenerative potential. Using low-input multi-omics, we systematically profiled the epigenome, transcriptome, and 3D genome of MuSCs from individual mice across 3 age groups (young, old, and geriatric) and both sexes. At baseline, young male MuSCs showed reduced expression of cell...
Different Pattern in Circulating MicroRNA-22-3p Levels Between Patients With Primary Versus Secondary Sarcopenia
Sarcopenia, characterized by decreased skeletal muscle mass and strength, is classified as "primary" (due to aging) or "secondary" (due to diseases). MicroRNA-22-3p (miR-22) regulates muscle differentiation and function. We assessed the diagnostic value of circulating miR-22 levels in patients with primary and secondary sarcopenia. miR-22 levels were evaluated in 61 older adults from the "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) study and...
Unlocking rejuvenating potential of mesenchymal progenitor cells
Age-dependent exhaustion of endogenous stem cell pools-and the resulting decline in tissue regeneration and homeostatic maintenance-is a hallmark of organismal aging and age-related pathology. In a study published in Cell, Liu and collaborators engineered human ESC-derived mesenchymal progenitor cells to give the ability to resist senescence, environmental stress, and malignant transformation.
Targeted clearance of senescent cells alleviates alcohol-associated liver disease by restoring cellular function and immune balance
The liver is one of the organs most affected by alcohol consumption, and its interaction with aging is particularly significant. Chronic alcohol consumption accelerates liver aging through mechanisms such as oxidative stress, inflammation, fibrosis, and impaired regeneration. It is still unknown whether senescent cell clearance orchestrates innate and adaptive immune responses during the alcohol-induced old liver damage process. To investigate this, we used INK-ATTAC transgenic mice treat with...
Factors predicting holistic nursing competence in a sample of nurses caring for older adults
CONCLUSIONS: The findings of this study indicate that HNC in the care of older adults is influenced by ethical competencies, attitudes towards aging, professional training, and work-related environmental factors. Therefore, developing structured in-service training programs, promoting ethical conduct in nursing, and reducing ageist attitudes are considered effective strategies for enhancing HNC. The results of this research can inform policies in nursing education and human resource development.
Bridging single cells to organs: Mesoscale modules as fundamental units of tissue function
Recent studies at molecular and genomic scales have enriched our understanding of life's most fundamental building block: the cell. However, bridging the gap between single-cell phenotypes and the emergent functions of tissues and organs remains a formidable challenge. Here, we suggest that the conceptual span from cells to tissues and organs is so large as to warrant intermediate stepping stones. Drawing inspiration from "network motifs"-discrete units of cell-level function that emerge from...
Telomerase-Active Urine-Derived Stem Cells: Regenerative Solutions for Aging
Aging is a complex process that leads to various pathologies and poses a significant socioeconomic challenge. Stem cell therapies offer a promising avenue for intervention, primarily through mechanisms like telomere maintenance and cellular rejuvenation. However, conventional stem cell sources often come with limitations such as invasive collection, ethical concerns, safety risks, and high costs, which impede their clinical application. Urine-derived stem cells (USCs), in contrast, present an...
Fibroblast growth factor signaling induces a chondrocyte-like state of peripheral nerve fibroblast during aging
During aging, peripheral nerves undergo structural and cellular changes that trigger loss of function, impair quality of life, and increase disease risk. During peripheral nerve aging there are cellular and molecular changes, such as increased extracellular matrix deposition. The mechanisms behind these aging-induced alterations remain unclear. Here, we profile mouse sciatic nerves using single nucleus transcriptomics and unravel changes in macrophage subtypes during nerve aging. Phagocytic...
AAV-mediated BDNF and GAS6 muscle delivery delays disease onset in SOD1<sup>G93A</sup> ALS mice
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, with limited treatments. Gene therapy offers an alternative strategy for treating a large portion of ALS patients, however, the disparate genetic alterations in ALS complicate the development of gene therapies. Tyrosine receptor kinase B (TRKB) and Tyro3 receptors are highly expressed in mouse spinal cord motor neurons, suggesting that their ligands, brain-derived neurotrophic factor (BDNF) and growth arrest-specific 6...
Sex differences in behavior, immune function, and redox state throughout life, and their effect on the longevity of Swiss mice
Homeostatic systems (nervous, immune, and endocrine) are crucial for maintaining health throughout life and, consequently, relevant for the rate of aging and the longevity achieved. In many species, male and female mammals show different lifespans, attributed to distinct redox states, but it is scarcely known whether sex differences in the functioning of these systems are involved. This study investigated, in an integrative view, sex differences in the nervous and immune systems of Swiss strain...
Role of age in the association of chronic conditions and multimorbidity with incident ADL disability: multicohort analyses of 108,810 adults
Chronic conditions and multimorbidity are increasingly prevalent in ageing populations, and their impact on disability remains poorly understood. This study investigated the association of chronic conditions and multimorbidity at ages 50, 60, 70, and 80 years with the subsequent onset of disability. Data from 108,810 participants (54% women, mean age 61.2 ± 9.8 at baseline) from the Health and Retirement Study, the English Longitudinal Study of Ageing, and the Survey of Health, Ageing, and...
Early loss of astrocyte p38alpha MAPK reduces hippocampal neuroinflammation, enhances synaptic strength, and increases non-synaptic mitochondrial uncoupling in female mice during non-pathological aging
The p38 mitogen-activated protein kinase has a well-characterized role in modulation of inflammatory processes throughout the body. In the central nervous system, p38 is primarily studied within neurons and microglia, most commonly in the context of neurological insult. The present study was designed to determine its function in astrocytes during non-pathological aging. We generated a conditional knockout model in which a tamoxifen-inducible Aldh1l1 promoter drives Cre recombinase expression in...
CD21 primes extrafollicular differentiation of autoreactive B cells in a TLR7-driven lupus model
The extrafollicular (EF) B cell differentiation pathway has emerged as a prominent source of autoantibody-secreting cells (ASCs) in systemic lupus erythematosus (SLE). CD21^(lo)CD11c^(+) B cells are associated with aging, infection, and autoimmunity. They are key contributors to EF ASCs, yet their developmental trajectory and receptor programming are unclear. To study EF mechanics of autoreactive B cells, we adoptively transferred naïve B cell populations into 564Igi mice, which act as an...
Blocking nuclear receptor Nr4a3 unlocks the senescence barrier to promote direct cardiac reprogramming
Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) offers a regenerative strategy for heart repair, but efficiency declines in adult and aged cells. Transcriptomic and epigenetic profiling identified cellular senescence as a major barrier limiting cardiac fibroblast (CF) plasticity and cardiogenic conversion. Postneonatal fibroblasts exhibited impaired activation of cardiac gene programs and persistent expression of fibrotic and inflammatory signatures. A loss-of-function...
Elevated DNA damage without signs of aging in the short-sleeping Mexican cavefish
Dysregulated sleep has widespread health consequences, including the accumulation of DNA damage. The Mexican tetra, Astyanax mexicanus, provides a powerful model to study the evolution and consequences of sleep loss. Multiple cave-adapted populations of this species have independently evolved reduced sleep compared to surface populations, yet show no obvious decline in healthspan or longevity. To examine whether evolved sleep loss is associated with DNA damage, we compared DNA damage response...
Contrasting negative stereotypes against aging through a silent disco event: an ecological study
CONCLUSIONS: Silent Disco events show potential in challenging stereotypes and fostering inclusivity, but additional strategies are needed to promote deeper intergenerational engagement and social inclusion.
An intricate relationship: stress markers and associative memory in a laboratory experiment in older adults
INTRODUCTION: Researchers working in the field of cognitive aging frequently encounter highly motivated yet nervous older participants during data collection in the laboratory. Such anecdotal experiences raise the question of whether the affective or physiological response of older participants to psychological laboratory experiments differs to that of young adults, who might be less motivated but also less nervous, as they may be more used to the environment and to learning and memory tests.
Successful aging among older adults with and without disability
OBJECTIVES: Disability is a common experience in older adulthood, yet biomedical perspectives do not accommodate successful aging within the context of disability. Our study integrates disability into the concept of successful aging and utilizes subjective well-being and self-rated health as indicators of successful aging. Further, we establish the link between disability and successful aging. Finally, we consider the potential for modifiable factors that hold promise in fostering successful...
Age, caste, and social context shape ovarian morphology and transcriptomic profiles in red harvester ants
The reproductive division of labor defines eusocial insects like ants, where queens reproduce and workers remain sterile. Yet, some workers retain rudimentary ovaries, raising questions about latent reproductive potential. We examined morphological and transcriptomic differences in Pogonomyrmex barbatus queen and worker ovaries at different maturation stages and social contexts. Queens had large, yolk-rich oocytes, while worker ovaries showed regression. Callow workers (<5 days) had more...
Mitochondrial dysfunction drives age-related degeneration of the thoracic aorta
This study investigated the role of mitochondrial function in aortic aging. As the aorta ages, it becomes stiffer and less compliant, increasing the risk of aneurysmal disease, hypertension, and diastolic dysfunction. Given the role of mitochondrial dysfunction in non-age related aortopathies and as a hallmark of aging, we investigated its contribution to the aging aorta. Both male and female young (5-6 month) and aged (24-25 month) C57Bl/6 J mice received mitochondrial-targeted peptide...
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