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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...
CHCHD2 mutant mice link mitochondrial deficits to PD pathophysiology
Mitochondrial dysfunction is a hallmark of Parkinson's disease (PD), but the mechanisms by which it drives autosomal dominant and idiopathic forms of PD remain unclear. To investigate this, we generated and performed a comprehensive phenotypic analysis of a knock-in mouse model carrying the T61I mutation in the mitochondrial protein CHCHD2 (coiled-coil-helix-coiled-coil-helix domain-containing 2), which causes late-onset symptoms indistinguishable from idiopathic PD. We observed pronounced...
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...
Mammoth mummies up to 50,000 years old yield oldest RNA yet found
Ancient RNA promises to shed light on how genes functioned in extinct animals
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.