Aging & Longevity

Evaluating Senescence-Targeted Approaches in Alzheimer's Disease: What We Know and What Lies Ahead

4 days 1 hour ago
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, which represents the most prevalent dementia worldwide. Although amyloid-β (Aβ) and tau pathology have been the classic focus of treatment, accumulating evidence indicates that ageing-associated cellular senescence plays a central role in AD pathogenesis. Senescent neurons, astrocytes, microglia and endothelial cells accumulate in the ageing and Alzheimer's brain and adopt a senescence-associated secretory...
Pratik Prashant Doshi

Divergent aging of nulliparous and parous mammary glands reveals IL33+ hybrid epithelial cells

4 days 1 hour ago
Aging increases breast cancer risk while an early first pregnancy reduces a woman's life-long risk. Several studies have explored the effect of either aging or pregnancy on mammary stem/progenitor cells, however, the combined effect of both remains unclear. Here, we interrogate the functional and transcriptomic changes at single-cell resolution in the mammary gland of aged nulliparous and parous mice to discover that pregnancy normalizes age-related imbalances in lineage composition, while also...
Andrew Olander

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

4 days 1 hour 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

4 days 1 hour 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

4 days 1 hour 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

4 days 1 hour 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

4 days 1 hour 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

5 days 1 hour 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

5 days 1 hour 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

5 days 1 hour 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

5 days 1 hour 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

5 days 1 hour 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
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