Aging & Longevity

Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles

8 hours 15 minutes ago
The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, metabolomics and RNAseq of cardiac tissue from naked mole-rats was compared to other African mole-rat genera (Cape, Cape dune, Common, Natal, Mahali, Highveld and Damaraland mole-rats) and evolutionarily divergent mammals (Hottentot golden mole and...
Chris G Faulkes

The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease

8 hours 15 minutes ago
We have previously identified a network of higher-order brain regions particularly vulnerable to the ageing process, schizophrenia and Alzheimer's disease. However, it remains unknown what the genetic influences on this fragile brain network are, and whether it can be altered by the most common modifiable risk factors for dementia. Here, in ~40,000 UK Biobank participants, we first show significant genome-wide associations between this brain network and seven genetic clusters implicated in...
Jordi Manuello

Formation of memory assemblies through the DNA-sensing TLR9 pathway

8 hours 15 minutes ago
As hippocampal neurons respond to diverse types of information¹, a subset assembles into microcircuits representing a memory². Those neurons typically undergo energy-intensive molecular adaptations, occasionally resulting in transient DNA damage^(3-5). Here we found discrete clusters of excitatory hippocampal CA1 neurons with persistent double-stranded DNA (dsDNA) breaks, nuclear envelope ruptures and perinuclear release of histone and dsDNA fragments hours after learning. Following these early...
Vladimir Jovasevic

Single-cell multiplex chromatin and RNA interactions in ageing human brain

8 hours 15 minutes ago
Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA^(1-3). Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells^(4-7). Here we introduce the multinucleic acid interaction mapping in single cells (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression and...
Xingzhao Wen

Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity

8 hours 15 minutes ago
Ageing of the immune system is characterized by decreased lymphopoiesis and adaptive immunity, and increased inflammation and myeloid pathologies^(1,2). Age-related changes in populations of self-renewing haematopoietic stem cells (HSCs) are thought to underlie these phenomena³. During youth, HSCs with balanced output of lymphoid and myeloid cells (bal-HSCs) predominate over HSCs with myeloid-biased output (my-HSCs), thereby promoting the lymphopoiesis required for initiating adaptive immune...
Jason B Ross

The HEAT repeat protein HPO-27 is a lysosome fission factor

8 hours 15 minutes ago
Lysosomes are degradation and signalling centres crucial for homeostasis, development and ageing¹. To meet diverse cellular demands, lysosomes remodel their morphology and function through constant fusion and fission^(2,3). Little is known about the molecular basis of fission. Here we identify HPO-27, a conserved HEAT repeat protein, as a lysosome scission factor in Caenorhabditis elegans. Loss of HPO-27 impairs lysosome fission and leads to an excessive tubular network that ultimately...
Letao Li

Fructose-1,6-bisphosphatase 1 dephosphorylates and inhibits TERT for tumor suppression

8 hours 15 minutes ago
Telomere dysfunction is intricately linked to the aging process and stands out as a prominent cancer hallmark. Here we demonstrate that telomerase activity is differentially regulated in cancer and normal cells depending on the expression status of fructose-1,6-bisphosphatase 1 (FBP1). In FBP1-expressing cells, FBP1 directly interacts with and dephosphorylates telomerase reverse transcriptase (TERT) at Ser227. Dephosphorylated TERT fails to translocate into the nucleus, leading to the inhibition...
Min Li

TREM1 disrupts myeloid bioenergetics and cognitive function in aging and Alzheimer disease mouse models

8 hours 15 minutes ago
Human genetics implicate defective myeloid responses in the development of late-onset Alzheimer disease. A decline in peripheral and brain myeloid metabolism, triggering maladaptive immune responses, is a feature of aging. The role of TREM1, a pro-inflammatory factor, in neurodegenerative diseases is unclear. Here we show that Trem1 deficiency prevents age-dependent changes in myeloid metabolism, inflammation and hippocampal memory function in mice. Trem1 deficiency rescues age-associated...
Edward N Wilson

TP53INP2-dependent activation of muscle autophagy ameliorates sarcopenia and promotes healthy aging

8 hours 15 minutes ago
Sarcopenia is a major contributor to disability in older adults, and thus, it is key to elucidate the mechanisms underlying its development. Increasing evidence suggests that impaired macroautophagy/autophagy contributes to the development of sarcopenia. However, the mechanisms leading to reduced autophagy during aging remain largely unexplored, and whether autophagy activation protects from sarcopenia has not been fully addressed. Here we show that the autophagy regulator TP53INP2/TRP53INP2 is...
David Sebastián

The cryo-EM structure of ASK1 reveals an asymmetric architecture allosterically modulated by TRX1

1 day 8 hours ago
Apoptosis signal-regulating kinase 1 (ASK1) is a crucial stress sensor, directing cells toward apoptosis, differentiation, and senescence via the p38 and JNK signaling pathways. ASK1 dysregulation has been associated with cancer and inflammatory, cardiovascular, and neurodegenerative diseases, among others. However, our limited knowledge of the underlying structural mechanism of ASK1 regulation hampers our ability to target this member of the MAP3K protein family towards developing therapeutic...
Karolina Honzejkova

Autophagy maintains endosperm quality during seed storage to preserve germination ability in Arabidopsis

2 days 8 hours ago
To preserve germination ability, plant seeds must be protected from environmental stresses during the storage period. Here, we demonstrate that autophagy, an intracellular degradation system, maintains seed germination ability in Arabidopsis thaliana. The germination ability of long-term (>5 years) stored dry seeds of autophagy-defective (atg) mutant and wild-type (WT) plants was compared. Long-term stored (old) seeds of atg mutants showed lower germination ability than WT seeds, although...
Daiki Shinozaki

Fire suppression makes wildfires more severe and accentuates impacts of climate change and fuel accumulation

2 days 8 hours ago
Fire suppression is the primary management response to wildfires in many areas globally. By removing less-extreme wildfires, this approach ensures that remaining wildfires burn under more extreme conditions. Here, we term this the "suppression bias" and use a simulation model to highlight how this bias fundamentally impacts wildfire activity, independent of fuel accumulation and climate change. We illustrate how attempting to suppress all wildfires necessarily means that fires will burn with...
Mark R Kreider

Risk factors associated with heatwave mortality in Chinese adults over 65 years

2 days 8 hours ago
Aging populations are susceptible to heat-related mortality because of physiological factors and comorbidities. However, the understanding of individual vulnerabilities in the aging population is incomplete. In the Chinese Longitudinal Healthy Longevity Survey, we assessed daily heatwave exposure individually for 13,527 participants (median age = 89 years) and 3,249 summer mortalities during follow-up from 2008 to 2018. The mortality risk during heatwave days according to relative temperature is...
Di Xi

Combinatorial transcriptomic and genetic dissection of insulin/IGF-1 signaling-regulated longevity in Caenorhabditis elegans

2 days 8 hours ago
Classical genetic analysis is invaluable for understanding the genetic interactions underlying specific phenotypes, but requires laborious and subjective experiments to characterize polygenic and quantitative traits. Contrarily, transcriptomic analysis enables the simultaneous and objective identification of multiple genes whose expression changes are associated with specific phenotypes. Here, we conducted transcriptomic analysis of genes crucial for longevity using datasets with...
Seokjin Ham

Human alpha-synuclein overexpression upregulates SKOR1 in a rat model of simulated nigrostriatal ageing

2 days 8 hours ago
Parkinson's disease (PD) is characterised by progressive loss of dopaminergic (DA) neurons from the substantia nigra (SN) and α-synuclein (αSyn) accumulation. Age is the biggest risk factor for PD and may create a vulnerable pre-parkinsonian state, but the drivers of this association are unclear. It is known that ageing increases αSyn expression in DA neurons and that this may alter molecular processes that are central to maintaining nigrostriatal integrity. To model this, adult female...
Noelia Morales-Prieto

Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan in Saccharomyces cerevisiae

3 days 8 hours ago
A major consequence of aging and stress, in yeast to humans, is an increased accumulation of protein aggregates at distinct sites within the cells. Using genetic screens, immunoelectron microscopy, and three-dimensional modeling in our efforts to elucidate the importance of aggregate annexation, we found that most aggregates in yeast accumulate near the surface of mitochondria. Further, we show that virus-like particles (VLPs), which are part of the retrotransposition cycle of Ty elements, are...
K L Schneider
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