Aggregator

Beyond their role in energy production, mitochondria also interact with other organelles through forming membrane contacts that serve as central hubs of cellular metabolism and signaling. Aberrant mitochondria-organelle communication has been implicated in various neurodegenerative diseases, but the underlying mechanisms and their pathological consequences remain poorly understood. Here, we reveal that tauopathy synapses exhibit excessive tethering of autophagosome/autophagic vacuole...

CONCLUSION: Higher SES was associated with higher QOL. Older age and widowhood were also associated with lower QOL. Thus, enhancing financial support, expanding social services, and prioritizing the socioeconomically disadvantaged and widowed elderly may contribute to promoting equitable and healthy aging.

CONCLUSIONS: Artificial intelligence holds significant promise for mitigating the global geriatric healthcare crisis exacerbated by demographic aging and nursing shortages. However, realizing its full potential requires a coordinated, multi-stakeholder approach to overcome the entrenched systemic, human, and social obstacles. The proposed roadmaps provide an actionable framework that may facilitate the development of artificial intelligence systems that are more efficient, equitable, and...

No abstract

CONCLUSION: These findings identify gaze fixation as a key determinant of increased spin-turn use during turning in older adults, whereby constraining gaze to the near walking surface alters visual information available for step planning and promotes maladaptive turning strategy selection.

Scientists may have uncovered a hidden trigger behind Alzheimer’s disease. Instead of plaques being the root cause, amyloid beta appears to interfere with tau, a protein that helps keep neurons functioning properly. This disruption could set off the damage that eventually leads to the disease’s most recognizable brain changes.

Plague was already a deadly killer 5,500 years ago, long before cities, farming, or the rat-infested conditions usually linked to historic outbreaks. By analyzing ancient DNA from hunter-gatherer cemeteries in Siberia, researchers discovered early plague strains in nearly 40% of the individuals studied and found evidence of rapid family-based outbreaks that wiped out many children and young teenagers.

In this issue of Molecular Cell, Sohn et al.¹ explore how endogenous dsRNAs influence organismal aging and identify an unexpected function of the aminoacyl-tRNA synthetase FARS-1/FARSA in regulating mitochondrial dsRNA homeostasis to balance longevity and innate immunity.

Increasing evidence suggests that epigenetic dysregulation is both a hallmark and a potential driving force of aging. As a multifactorial, non-linear, and systemic biological process, aging likely results from a progressive imbalance in a complex epigenetic network involving DNA, histones, RNA, and non-coding sequences. These interconnected alterations collectively lead to core aging features such as genomic instability, heightened inflammation, and loss of cellular identity. In this review, we...

CONCLUSIONS: Cardiometabolic biomarker domains, particularly glycaemic dysfunction, were reproducibly associated with incident mobility limitation. A simple biomarker-burden score captured a relevant but incomplete component of functional ageing risk.

Obesity increases the risk of common diseases and mortality, placing a significant burden on our aging society. Bariatric surgery results in significant weight loss; however, the amount of associated health gain is currently less studied, particularly in the first two years. We modelled mortality-associated biological age according to established blood markers in a prospective cohort of 505 patients that underwent bariatric surgery. The difference between biological age and chronological age...

Cellular senescence is a highly heterogeneous state of cell stress response that deleteriously accumulates with age and contributes to age-related dysfunction. While the heterogeneity across cell types is well documented, variation within the same cell type is only beginning to be understood. Here, we show primary human lung fibroblasts from either donors who are healthy or diagnosed with idiopathic pulmonary fibrosis (IPF) exhibit a subtle form of heterogeneity over time after DNA damage....

Hippocampal volume is associated with memory and is critical in Alzheimer's disease, but few studies have examined hippocampal subfield volume changes during healthy aging. Herein, we utilize submillimeter MRI to examine age- and sex-specific subfield volumetric changes in 206 participants (M(age) = 53.05 years, range = 21-87, N(female) = 110). Total intracranial volume was regressed out and hierarchical regression was performed to examine subfield volume changes with age. To identify inflection...

Radiotherapy (RT) efficacy is limited by RT-induced immune resistance. Here we show that RT upregulates programmed death ligand 1 (PD-L1) on senescent tumor cells (STCs) via bromodomain-containing protein 4 (BRD4) signaling, thereby promoting immune evasion. To counter this, we develop POLY-Senolytic, a polymeric senolytic nanoparticle formed by conjugating an acid-responsive polymer to a peptide-based BRD4 PROteolysis-TArgeting Chimera via a reduction-cleavable disulfide bond. The...

Life is a constant struggle against disorder. As we age, our ability to maintain internal order declines. In the healthy human brain, order is observable in the form of functionally segregated brain network communities that exhibit spatial consistency. These communities associate with distinct cognitive and physical functions. When mapped into the brain, they form a functional "landscape". We assessed the spatial disorder of these landscapes in older adults with a wide range of mobility using a...

Phosphatidylinositol 3-kinase (PI3K) integrates insulin/IGF signaling (IIS) and Ras inputs to control lifespan, metabolism and growth. Yet the organismal consequences of selective structural perturbations remain poorly understood. Using structure-guided CRISPR/Cas9-dependent genome editing, we dissected functions of AGE-1, the sole Class IA PI3K catalytic subunit in Caenorhabditis elegans. An endogenously tagged AGE-1, containing a long flexible linker, epitope and fluorescent tag, retained full...

Reducing protein synthesis extends lifespan across taxa, but pharmacological strategies to safely attenuate translation remain limited. Tetracyclines are clinically used antibiotics long observed to exert beneficial effects in age-associated diseases and extend lifespan in model organisms, though the underlying mechanisms remain unclear. Here, we systematically profiled commercially available tetracyclines and show that translation attenuation is a general property of the tetracycline class....

Deterioration of the blood-brain barrier (BBB), including impaired neurovascular uncoupling, contributes to cognitive decline in aging. The BBB is formed principally by brain microvascular endothelial cells (ECs), and ECs throughout the body are enriched for the transcription factor Krüppel-like factor 4 (KLF4). Because KLF4 levels in ECs decrease with age, we tested whether that decline contributes to aging-related BBB deterioration, neurovascular dysfunction, and cognitive impairment. Using...

Age and early life adversity (ELA) are key determinants of health, but whether they affect similar physiological mechanisms across tissues is unknown. We generated DNA methylation (DNAm) profiles across 14 tissues in 237 semi-free-ranging rhesus macaques with naturally occurring ELA. Age-associated DNAm was predominantly tissue dependent, yet tissue-specific epigenetic clocks showed that epigenetic aging was relatively consistent within individuals. ELA effects were adversity dependent, but each...