Senescent glia link mitochondrial dysfunction and lipid accumulation.

Senescence is a cellular state linked to ageing and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumour formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. Whereas senescent cells are active targets for anti-ageing therapy, why these cells form in vivo, how they affect tissue ageing and the effect of their elimination remain unclear.

Cell type-specific regulation of m A modified RNAs in the aging Drosophila brain.

The aging brain is highly vulnerable to cellular stress, and neurons employ numerous mechanisms to combat neurotoxic proteins and promote healthy brain aging. The RNA modification m A is highly enriched in the Drosophila brain and is critical for the acute heat stress response of the brain. Here we examine m A in the fly brain with the chronic stresses of aging and degenerative disease.

TDP-43 impairs sleep in through -dependent metabolic disturbance.

Neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia are associated with substantial sleep disruption, which may accelerate cognitive decline and brain degeneration. Here, we define a role for trans-activation response element (TAR) DNA binding protein 43 (TDP-43), a protein associated with human neurodegenerative disease, in regulating sleep using . Expression of TDP-43 severely disrupts sleep, and the sleep deficit is rescued by knockdown.

dTrmt10A impacts Hsp70 chaperone mA levels and the stress response in the Drosophila brain.

Chronic cellular stress has a profound impact on the brain, leading to degeneration and accelerated aging. Recent work has revealed the vital role of RNA modifications, and the proteins responsible for regulating them, in the stress response. In our study, we defined the role of CG14618/dTrmt10A, the Drosophila counterpart of human TRMT10A a N-methylguanosine methyltransferase, on mA regulation and heat stress resilience in the Drosophila brain.

A neural circuit for vocal production responds to viscerosensory input in the songbird.

Motor performance is monitored continuously by specialized brain circuits and used adaptively to modify behavior on a moment-to-moment basis and over longer time periods. During vocal behaviors, such as singing in songbirds, internal evaluation of motor performance relies on sensory input from the auditory and vocal-respiratory systems. Sensory input from the auditory system to the motor system, often referred to as auditory feedback, has been well studied in singing zebra finches (), but little is known about how and where nonauditory sensory feedback is evaluated.

mA in CAG repeat RNA binds to TDP-43 and induces neurodegeneration.

Microsatellite repeat expansions within genes contribute to a number of neurological diseases. The accumulation of toxic proteins and RNA molecules with repetitive sequences, and/or sequestration of RNA-binding proteins by RNA molecules containing expanded repeats are thought to be important contributors to disease aetiology. Here we reveal that the adenosine in CAG repeat RNA can be methylated to N-methyladenosine (mA) by TRMT61A, and that mA can be demethylated by ALKBH3.

Mettl3-dependent mA modification attenuates the brain stress response in Drosophila.

N-methyladenosine (mA), the most prevalent internal modification on eukaryotic mRNA, plays an essential role in various stress responses. The brain is uniquely vulnerable to cellular stress, thus defining how mA sculpts the brain's susceptibility may provide insight to brain aging and disease-related stress. Here we investigate the impact of mA mRNA methylation in the adult Drosophila brain with stress.

Toxicity of pathogenic ataxin-2 in Drosophila shows dependence on a pure CAG repeat sequence.

Spinocerebellar ataxia type 2 is a polyglutamine (polyQ) disease associated with an expanded polyQ domain within the protein product of the ATXN2 gene. Interestingly, polyQ repeat expansions in ATXN2 are also associated with amyotrophic lateral sclerosis (ALS) and parkinsonism depending upon the length of the polyQ repeat expansion. The sequence encoding the polyQ repeat also varies with disease presentation: a pure CAG repeat is associated with SCA2, whereas the CAG repeat in ALS and parkinsonism is typically interrupted with the glutamine encoding CAA codon.