Aging & Longevity

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...

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...

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...

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...

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...

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...

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.

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.

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...

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...

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...

CONCLUSIONS: Notwithstanding psychometric and measurement issues, this review provides a comprehensive summary of existing instruments assessing subjective VoA, which have clinical and applied utility in promoting healthy aging, especially for older adults at risk of pathological aging. The development and validation of new VoA scales, particularly to assess views on age-related cognitive changes with aging, is warranted.

Coffee is one of the most widely consumed beverages in the world and is a rich source of caffeine, a methylxanthine. Here we show that exposure to caffeine significantly reduces ionizing radiation (IR) induced DNA breaks and resulted in no or minimal G2/M arrest within the human cell, in contrast to IR alone. At the molecular level, we demonstrate that when naked plasmid DNA or oligomeric DNA was irradiated, the number of breaks was significantly less in the presence of caffeine. The observed...

Healthspan, the disease-free period of life, has become a central focus in aging research. Cuscuta chinensis seed and Eucommia ulmoides bark extracts, two traditional Chinese medicine (TCM) remedies, have shown promising healthspan-extending effects in Caenorhabditis elegans. In this study, RNA-seq analysis of aged worms treated with these extracts revealed significant transcriptomic alterations. Gene ontology and KEGG pathway analyses indicated upregulation of genes involved in immune defense,...

Aging is associated with skeletal muscle weakness and oxidative stress. Here, we hypothesized that aging may lead to alterations in adrenoceptor (AR)-dependent regulation of muscle contractility. These changes can aggravate muscle contractile dysfunction and correlate with redox disturbances. Glycolytic extensor digitorum longus (EDL) and oxidative soleus muscles from young adult (3 months), middle-aged (12 months), and old (24 months) mice were used. Contractile responses were elicited by...

CONCLUSION: The study highlights the gradual loss of the significant directed causal connections between the control and motor networks in different stages of PD. The governing influence of control network over the motor and attentional networks diminishes, leading to the isolation of the somatomotor network. The ability of TPDC-derived features to distinguish prodromal from Parkinson's patients underscores its value for identifying potential biomarkers of disease onset and progression.

In human populations, cognitive performance in early life has been identified as a strong predictor of future dementia risk. If cognitive ability were a stable trait across the adult lifespan of mice, then this species would provide an excellent framework for understanding the biology underlying this modifiable risk factor. To address this issue, longitudinal cognitive testing was performed in female C57BL/6J mice aged between 4 and 18 months of age. By tracking individuals, we were able to...

Entropy, a measure of disorder and randomness, is an essential feature of thermodynamics, chemistry, and information theory, but there has been little study of entropy in human aging. Entropy arises from random molecular interactions or other forms of damage and will manifest at all levels of human biology. It should also progress in concert across many systems and increase the risk of numerous aging-related conditions. Illustrating these principles, research by Hong in this issue of Aging Cell...

Telomerase, crucial for maintaining telomere integrity and genomic stability, is typically silenced in somatic cells with advancing age. In this study, we identify circHERC1 as a regulator of telomerase reverse transcriptase (TERT) transcription. Specifically, circHERC1 binds to the TERT promoter, facilitating the recruitment of RNA polymerase II and c-Fos, thereby activating TERT expression. Notably, circHERC1 expression exhibits a decline with age, which correlates with reduced telomerase...

Glycogen storage disease (GSD) type IX γ2 is a rare inborn error of metabolism where a defect in glycogenolysis leads to the inability to break down glycogen in the liver. Patients with GSD IX γ2 develop hypoglycemia and advanced liver disease, placing them at risk for liver transplantation. This study evaluates the efficacy of liver-directed AAV gene therapy in a murine model of GSD IX γ2. Phkg2^(-/-) mice underwent treatment with AAV gene therapy (AAV9-LSP-mPhkg2, 5 × 10^(12) vg/kg,...