Aging & Longevity

Regulated cell death (RCD) shapes neoplastic transformation, tumor progression, and response to treatment. While apoptosis was long viewed as the only RCD variant, additional modalities, including necroptosis, pyroptosis, and ferroptosis, have been characterized. These interconnected pathways operate in a context-dependent manner to influence the dynamic interplay between malignant and non-malignant cells that governs disease progression or regression, both naturally and during therapy. Major...

Age-related muscle dysfunction is a major contributor to disability, frailty, and poor clinical outcomes in older adults. Skeletal Muscle Function Deficit (SMFD) framework integrates multiple domains as: muscle mass, muscle density, strength, and power to capture a broader spectrum of age-related muscle dysfunction. The primary aims of these analyses are to develop and validate a composite SMFD score and evaluate its association with key geriatric outcome. This study used data from the InCHIANTI...

Myocytes are exceptionally long-lived cells that must maintain proteome integrity over decades while adjusting for changes in functional output and metabolic demand. We used in vivo stable isotope labeling combined with mass spectrometry proteomics and correlated multi-isotope imaging mass spectrometry to quantify and visualize protein turnover across cardiac, fast-twitch, and slow-twitch skeletal muscles, creating a resource of hundreds of individual protein turnover rates from each tissue. We...

Cells terminally arrested in the cell cycle that exhibit a distinct secretory phenotype are referred to as senescent. These cells play a complex role during tumor progression; they can inhibit or promote tumor growth depending on disease stage. We developed a mouse model that allows monitoring and selective elimination of cells expressing high levels of the cyclin-dependent kinase inhibitor p16 and interleukin-6. These mice, termed SuSe (suicidal senescence), were crossed with the mouse mammary...

CONCLUSION: Adherence to a healthy diet may contribute to reducing the premature aging risk in adult survivors of childhood cancer. Interventions that support healthy eating in this population could potentially have benefits for long-term health outcomes.

Defective nucleocytoplasmic transport (NCT) has emerged as a contributing factor in the pathogenesis of neurodegenerative diseases and aging. Valosin-containing protein (VCP) is an AAA+ATPase required for disassembly of protein complexes, and mutations in VCP cause neurodegenerative and neuromuscular diseases. We find that VCP is required for quality control of nuclear pore complexes (NPCs) by extracting selected nucleoporins from NPCs for proteasome-mediated degradation. Pathogenic VCP variants...

CONCLUSION: Our findings suggest a bidirectional relationship between MetS and EAA, with biological aging potentially mediating metabolic deterioration. EAA may serve as both a marker and mediator of metabolic health, and a promising target for prevention and intervention.

Insulin action on the skeleton is essential for bone development and whole-body energy metabolism, however a global view of signaling in this tissue is lacking. Furthermore, whether there are signaling differences that drive the gene-specific activation under insulin-resistant (IR) or ageing conditions is unknown. Here, we perform a phosphoproteomic analysis of insulin signaling in the bones of young, lean, insulin-sensitive versus old, obese, IR mice revealing a rewiring of phosphorylation. We...

Anopheles gambiae is one of the principal vectors of human malaria. Over the past two decades, transgenic mosquito strains have been essential tools for studying mosquito biology and developing genetic control strategies such as gene drives. Mosquito transformants are typically identified using fluorescent markers, which are assumed to be phenotypically neutral. While generating CRISPR-based gene drive strains carrying an OpIE2-DsRed marker we unexpectedly found that transgenic females were...

CONCLUSIONS: ε4 contributes to literacy decline among older adults, presumably due in part to the accumulation of neuropathologies associated with ε4. We discuss the potential clinical implications of ε4-related literacy decline.

CONCLUSIONS: A decision support tool for caregivers of PLwD that provides education about transitions in care site, along with support for the emotional aspects of decision making, is highly acceptable and supports caregivers' ability to engage with what can be a challenging topic.

CONCLUSIONS: In the Rugao Aging Cohort, significant gender differences of thickness of all macular layers between males and females were identified, with males exhibiting thicker inner rings and thinner outer rings compared to females. Notably, cognitive decline was associated with the thinning of the central part and inner ring of macula exclusively in females. These results suggest that when macular thickness is used as a risk marker for cognitive decline, its gender bias should be carefully...

Memory functions are susceptible to age-related cognitive decline, making it essential to explore the underlying neurophysiological mechanisms that contribute to memory function during healthy ageing. Resting-state EEG (rsEEG) parameters, particularly the aperiodic exponent, a marker of cortical excitation-inhibition balance, and individual alpha peak frequency, a correlate of neural processing efficiency, have demonstrated associations with ageing and cognitive functions. This study...

Aging is a progressive process characterized by cellular and molecular damage leading to mitochondrial dysfunction and cognitive decline. Mitochondrial dysfunction is a critical factor in memory impairment in aging and neurodegenerative diseases. While sex differences in aging have been observed across various species, the underlying cellular and molecular mechanisms remain poorly understood, mainly focused on mitochondrial proteostasis. This study examined hippocampal-dependent cognitive...

CONCLUSIONS: The population of nonagenarians was specific in causes of death and comorbidities. Improving end-of-life care for these patients can include a high access to specialist palliative care and symptoms management.

Chemotherapy-induced bone loss is a debilitating and common side effect of cancer treatment, though its underlying mechanisms remain poorly understood. Here, we show that, despite the systemic administration of chemotherapy, cellular senescence is restricted to bone marrow adipo-lineage cells specifically Cxcl12-abundant reticular (CAR) cells and bone marrow adipocytes (BMAds). Induction of senescence within these populations promotes RANK ligand (RANKL)-mediated osteoclastogenesis, leading to...

Aging is closely associated with cardiovascular diseases, the leading cause of mortality worldwide. Mitochondrial dysfunction is a hallmark of cardiovascular aging. Most of the heart's ATP is produced at the cristae, specialized subcompartments where oxidative phosphorylation (OXPHOS) takes place. In this study, we used multiple-scale electron microscopy approaches to evaluate age-related mitochondrial and ultrastructural alterations of cristae in human and mouse hearts. We found that aged...

Quantifying individual deviations in brain morphology from normative references is useful for understanding neurodiversity and facilitating personalized management of brain health. Here we report Chinese brain normative references using morphological imaging scans of 24,061 healthy volunteers from 105 sites, revealing later peak ages of lifespan neurodevelopmental milestones (1.2-8.9 years) than European/North American populations. We model individual brain deviation scores in 3,932 individuals...

CONCLUSIONS: Current research on MCR management is in its early stages and does not fully align with the integrated, proactive principles of the PHM framework. The evidence base is dominated by risk stratification and preliminary intervention studies, while foundational areas like health literacy and technological monitoring are less developed. Future work could focus on standardizing MCR assessment, addressing key gaps in the underrepresented PHM dimensions, and developing and testing...

Older adults are disproportionately affected by infectious diseases like influenza (flu) due to immune declines and poor vaccine responses. Senolytics have been shown to improve various age-related conditions and positively influence infection outcomes, yet their potential to enhance vaccine responses has not yet been explored. Here, we evaluated the potential of senolytic combination Dasatinib (D) and Quercetin (Q) treatment prior to influenza vaccination to potentiate immune responses in aged...