Aging & Longevity

PURE-seq integrates FACS and PIP-seq for single-cell genomics of ultra-rare cells

1 month ago
Single-cell transcriptomics is valuable for uncovering individual cell properties, particularly in heterogeneous systems. However, this technique often results in the reanalysis of many well-characterized cells, increasing costs and diluting rare cell populations. To address this, we develop PIP-seq for Rare-cell Enrichment and Sequencing (PURE-seq). PURE-seq allows direct FACS sorting of cells into PIP-seq reactions, minimizing handling and reducing cell loss. PURE-seq reliably sequences...
Sixuan Pan

Common variation in meiosis genes shapes human recombination and aneuploidy

1 month ago
The leading cause of human pregnancy loss is aneuploidy, often tracing to errors in chromosome segregation during female meiosis^(1,2). Although abnormal crossover recombination is known to confer risk for aneuploidy^(3,4), limited data have hindered understanding of the potential shared genetic basis of these key molecular phenotypes. To address this gap, we performed retrospective analysis of pre-implantation genetic testing data from 139,416 in vitro fertilized embryos from 22,850 sets of...
Sara A Carioscia

Ageing promotes microglial accumulation of slow-degrading synaptic proteins

1 month ago
Neurodegenerative diseases affect 1 in 12 people globally and remain incurable. Central to their pathogenesis is a loss of neuronal protein maintenance and the accumulation of protein aggregates with ageing^(1,2). Here we engineered bioorthogonal tools³ that enabled us to tag the nascent neuronal proteome and study its turnover with ageing, its propensity to aggregate and its interaction with microglia. We show that neuronal protein half-life approximately doubles on average between 4-month-old...
Ian H Guldner

Blood Cell Mitochondrial Respiration Increases With Age and Varies by Sex in Healthy Adults

1 month ago
Mitochondrial dysfunction is recognized as a biological hallmark of aging; however, bioenergetic capacity across the healthy human life course remains insufficiently characterized. While aging is generally associated with a systemic decline in mitochondrial function ("age-related bioenergetic decline"), recent research suggests that age-related bioenergetic differences are context dependent. Blood cells are extensively utilized as accessible samples for human bioenergetic profiling; therefore,...
Howard J Phang

Aging Reshapes gamma/delta T-Cell Immunity Through a Type I Interferon-Foxo1 Axis

1 month ago
Aging is associated with profound alterations in immune cell composition and function, yet the impact on peripheral γ/δ T-cell subsets remains incompletely understood. Here, we show that the peripheral γ/δ T-cell compartment is markedly remodeled with age in mice. Specifically, innate-like Ly-6C^(-) CD44^(hi) γ/δ T cells expand in secondary lymphoid organs (SLOs) of aged mice, while adaptive-like subsets decline. This age-related shift is accompanied by enhanced functionality, with Ly-6C^(-)...
Aurélie Durand

Proteolysis-targeting chimera (PROTAC): a promising senolytic strategy

1 month ago
Senescent cells (SCs) accumulate with aging and contribute to the development of age-related pathologies. These cells evade apoptosis through upregulation of senescent cell anti-apoptotic pathways (SCAPs), making their selective elimination, a strategy termed senolysis, a promising therapeutic avenue. Proteolysis-targeting chimeras (PROTACs) represent an emerging class of bifunctional molecules that exploit the ubiquitin-proteasome system to degrade specific target proteins. By concurrently...
Gang Fan

Behavioral and psychophysical characterization of proprioceptive impairment in healthy aging: a hyper-illusory experience of movement

1 month ago
Age-related deterioration of the sensorimotor system can impair proprioception. This study aimed to characterize age-related changes in the sense of position and movement. Three experiments involved two groups of participants (29 young adults and 26 older adults) to i) evaluate the performance in a position matching task (Experiment 1), ii) assess the perception and reproduction of an illusory movement evoked by proprioceptive stimulation (mechanical muscle-tendon vibration) (Experiment 2), and...
Francesco Mirabelli

Early-onset Palmijihwang-hwan treatment modulates phospholipid metabolism and gut microbiota for healthy aging: reducing adipose inflammation and oxidative stress

1 month ago
Aging is characterized by progressive physiological decline and increased vulnerability to metabolic and inflammatory disturbances. Palmijihwang-hwan (PM), a traditional East Asian herbal formula, has been used empirically for age-related complaints, but its mechanistic basis remains unclear. Here, we evaluated the effects of early-onset PM administration (starting at 2 months of age) on longevity-related phenotypes and metabolic regulation. PM significantly prolonged lifespan in Caenorhabditis...
So Min Lee

Conserved shifts in sperm small non-coding RNA profiles during mouse and human aging

1 month ago
Sperm aging impacts male fertility and offspring health, highlighting the need for reliable aging biomarkers to guide reproductive decisions. However, the molecular determinants of sperm fitness during aging remain ill-defined. Here, we profiled sperm small non-coding RNAs (sncRNAs) using PANDORA-seq, which overcomes RNA modification-induced detection bias to capture previously undetectable sncRNA species associated with mouse and human spermatozoa throughout the lifespan. We identified an...
Junchao Shi

Older adults can outperform younger adults in creative problem solving

1 month ago
CONCLUSION: These findings suggest that while aging is associated with some types of cognitive decline, it also fosters unique cognitive strengths that can enhance certain aspects of creativity. The findings of the current study underscore the need to reconsider stereotypes about aging and creativity and highlights the interplay of executive and associative processes in creative ideation.
Barbara Ozkalp-Poincloux

The Ess1 prolyl isomerase represses TERRA transcription and promotes telomere replication in Saccharomyces cerevisiae

1 month ago
The conserved Ess1 prolyl isomerase (PIN1 in human) binds the carboxy-terminal domain (CTD) of RNA Pol II, and plays multiple roles in transcription regulation. Consistent with an essential role of the human PIN1 in telomere maintenance, previous screenings have identified the yeast Ess1 as a telomere length maintenance gene. Here, we provide evidence that Ess1 is involved in regulating both telomere transcription and replication. We find that depletion of Ess1 leads to a failure in...
Juxiu Chen

Aging populations threaten conservation goals of zoos

1 month ago
Improvements in wildlife husbandry mean that many zoo animals are living longer. This has put pressure on the finite holding capacity of zoos, which has often been addressed through a curtailing of reproduction to reduce population growth rates. Here, we explore how such actions have impacted the demographic trends of 774 mammal populations in European and North American zoo populations between 1970 and 2023. Irrespective of whether the data are clustered by region, taxonomic group, conservation...
João Pedro Meireles
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