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Such prescient planning started 50,000 years earlier than thought, study finds

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Parkinson's disease (PD) is characterised by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Lewy bodies- the defining neuropathological hallmark of PD-are chiefly composed of aggregated forms of α-synuclein (α-syn). Despite the widespread presence of α-syn pathology, neurodegeneration is often selective, and the mechanisms underlying the vulnerability of specific neuronal populations in PD remain poorly understood. This review critically...

Ferroptosis promotes the progression of Parkinson's disease (PD) through its unique regulatory pathways. Biochanin A (Bioch A) has long attracted the attention of researchers due to its neuroprotective effects. However, whether Bioch A can treat PD by inhibiting ferroptosis and the underlying mechanism remain unclear. This study aimed to investigate whether Bioch A exerts a neuroprotective effect on PD by activating the Sirt1/Nrf2/GPX4 signaling pathway to inhibit ferroptosis. Behavior was...

Chronic systemic inflammation and DNA methylation changes are two major hallmarks of aging, yet their interaction is poorly known. We investigated the relation between circulating inflammatory proteome and epigenetic age acceleration as assessed by DNA methylation in four independent cohorts of different ages and health conditions. Epigenetic age scores known to predict human health span (GrimAge and PhenoAge) were more strongly associated with age-associated inflammatory proteins, frailty, and...

Inundations of pelagic Sargassum plague the tropical Atlantic, with size and impacts steadily increasing to surpass 30 million tons in 2025. Understanding the drivers of Sargassum growth in the so-called Great Atlantic Sargassum Belt is fundamental to developing effective mitigation strategies for affected nations. We present a nonlinear regression model that both explains the seasonal and interannual variability observed between 2011 and 2022 and predicts Sargassum concentrations in 2023 and...

Adipose tissues are highly dynamic in response to environmental temperature changes. During aging, subcutaneous white adipose tissues (WAT) decreases, yet whether this atrophy exacerbates cold stress and triggers systemic aging remains unclear. Here we show that adipocyte-specific expression of the Lmna^(G609G) mutation in male mice leads to progressive WAT atrophy, accelerates aging, and shortens lifespan, whereas female mice remain unaffected. This lipoatrophy exacerbates cold stress,...

CONCLUSIONS: The NCDs exacerbate healthcare inequities with socio-economically vulnerable older adult households at greater risk of CHE, impoverishment and worsened economic condition. Public funded health insurance programmes offered limited protection compared to private schemes.

CONCLUSION: Engaging in physical activity among the elderly South Asian population is affected by a complex mixture of individual, social, and cultural factors. For South Asians, it is important that interventions be implemented in a manner that meets the needs regarding capabilitymotivation, and support.

Spatial disorientation represents a clinically meaningful vulnerability during aging and is an early manifestation along the Alzheimer's disease continuum. Understanding how aging-related central nervous system (CNS) changes affect the neural computations required for spatial perspective taking (SPT) is essential for characterizing early neurodegenerative processes. In this study, older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD) completed a simplified...

Mitochondrial dysfunction is a prominent hallmark of aging contributing to the decline of metabolic plasticity in late life. While genetic distortions of mitochondrial integrity elicit premature aging, the mechanisms leading to "natural" aging of mitochondria are less clear. Here we use proteomics, lipidomics, genetics and functional tests in wild type Caenorhabditis elegans and long-lived clk-1(qm30) and isp-1(qm150) mitochondrial mutants to identify molecular pathways that support longevity...

Children who had cerebral malaria or severe malaria anemia have lower scores on tests measuring general cognition and math achievement

The nicotinamide adenine dinucleotide (NAD^(+)) hydrolase sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) is the central executioner of pathological axon degeneration and is allosterically activated by an increased nicotinamide mononucleotide (NMN)/NAD^(+) ratio. DNA damage induces NAD^(+) loss and an increased NMN/NAD^(+) ratio by hyperactivating poly(ADP-ribose) polymerase 1 (PARP1), which triggers the parthanatos cell death pathway. Multiple mechanistically distinct...

PINK1/Parkin-mediated mitophagy and other related mitochondrial quality control pathways are critical to maintaining cellular homeostasis and neuronal health, and indeed, mutations in PINK1 and PRKN that disrupt this pathway cause early-onset Parkinson's disease. While PINK1-dependent Parkin recruitment to damaged mitochondria has been established for over a decade, recent structural and biochemical advances have illuminated the mechanisms governing their allosteric activation and integration...

The spatiotemporal dynamics of hydrogen peroxide (H(2)O(2)) signaling and its effects on gene expression and cell fitness remain unclear. Using fission yeast, we applied genetic tools to control and monitor intracellular H(2)O(2) levels. We expressed the H(2)O(2) biosensor HyPer7 in four subcellular compartments, overexpressed D-amino acid oxidase (Dao1) in specific locations to induce localized H(2)O(2) production, and modulated H(2)O(2) detoxification or sensing. H(2)O(2) concentrations showed...

Cerebral ischemic small vessel disease (SVD) is a leading cause of vascular dementia and stroke. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common monogenic SVD, is caused by dominant missense mutations in Notch3 expressed in smooth muscle cells (SMCs) and pericytes. However, cell-type-specific contributions driving CADASIL remain unknown. Here, we generate two conditional knockin mouse models carrying the CADASIL-causing...