Aging & Longevity

A chaperone-proteasome-based fragmentation machinery is essential for aggrephagy

1 month ago
Perturbations in protein quality control lead to the accumulation of misfolded proteins and protein aggregates, which can compromise health and lifespan. One key mechanism eliminating protein aggregates is aggrephagy, a selective type of autophagy. Here we reveal that fragmentation is required before autophagic clearance of various types of amorphous aggregates. This fragmentation requires both the 19S proteasomal regulatory particle and the DNAJB6-HSP70-HSP110 chaperone module. These two...
Mario Mauthe

The interplay between circadian rhythms and aging: molecular mechanisms and therapeutic strategies

1 month ago
Circadian rhythms are essential biological systems operating on a 24-h cycle, playing a crucial role in regulating sleep, cognitive function, immune responses, and hormone secretion. This review explores the intricate relationship between circadian rhythms and aging, with a focus on the underlying molecular mechanisms. It discusses age-related changes in sleep patterns and the role of circadian disruption in the progression of neurodegenerative diseases such as Parkinson's and Alzheimer's....
Prashant Dhaka

JC Stand-by-U- development and evaluation of an in-home respite service model using mixed-method quasi-experimental design: study protocol

1 month ago
BACKGROUND: In an ageing society, most older adults who require long-term care are still living in their homes and communities. Their families are burdened by caregiving duties, but their unique needs are often overlooked. In response to the increasing needs of respite care, the Jockey Club Stand-by-U (JC Stand-by-U) Caregivers Community Support Project aims to study the family caregivers' needs and how to best support them in the context of Hong Kong.
Nga-Yan Hui

Heterozygous variants in <em>PLCG1</em> affect hearing, vision, cardiac, and immune function

1 month ago
Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP(2)) into inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG), important signaling molecules involved in many cellular processes including Ca^(2+) release from the endoplasmic reticulum (ER). PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here, we describe seven...
Mengqi Ma

Alteration of long- and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesis

1 month ago
Myeloid-biased hematopoiesis is a well-known age-related alteration. Several possibilities, including myeloid-biased hematopoietic stem cell (HSC) clones, may explain this. However, the precise mechanisms remain controversial. Utilizing the Hoxb5 reporter system to prospectively isolate long-term HSCs (LT-HSCs) and short-term HSCs (ST-HSCs), we found that young and aged LT-HSCs co-transplanted into the same recipients demonstrated nearly equivalent myeloid lineage output, contrary to the theory...
Katsuyuki Nishi

Zuogui and Yougui pills extend lifespan and improve ageing biomarkers via kaempferol-mediated mitophagy in Caenorhabditis elegans

1 month ago
Zuogui pill (ZGP) and Yougui pill (YGP) are classical kidney-tonifying formulas in Traditional Chinese Medicine, widely used clinically but with their potential to delay ageing and improve ageing biomarkers remaining unclear. This study combined network pharmacology and Caenorhabditis elegans models to investigate the anti-ageing effects and mechanisms of ZGP and YGP. Both formulas significantly extended lifespan (ZGP dose-dependently at 5-20 mg/mL; YGP at 20 mg/mL) and improved ageing...
Wendi Chen

An age-related decrease in leptin contributes to CD8(+) T cell aging in the tumor microenvironment

1 month 1 week ago
T cell dysfunction with age underlies an increased incidence of cancer in elderly individuals; however, how T cell aging is triggered in the tumor microenvironment is unclear. Here, we show that an age-associated reduction in adipocyte-derived leptin contributes to the accumulation of tumor-infiltrating senescent CD8^(+) T cells. Single-cell profiling of human and mouse cancer tissues reveals that the frequency of intratumoral senescent CD8^(+) T cells increases with age, leading to a weak...
Feixiang Wang

ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in mice

1 month 1 week ago
TANK-Binding Kinase 1 (TBK1) is involved in autophagy and immune signaling. Dominant loss-of-function mutations in TBK1 have been linked to Amyotrophic Lateral Sclerosis (ALS), Fronto-temporal dementia (FTD), and ALS/FTD. However, pathogenic mechanisms remain unclear, particularly the cell-type specific disease contributions of TBK1 mutations. Here, we show that deleting Tbk1 from mouse motor neurons does not induce transcriptional stress, despite lifelong signs of autophagy deregulations....
Isadora Lenoel

Mevalonate metabolites boost aged oocyte quality through prenylation of small GTPases

1 month 1 week ago
Declining oocyte quality is the major contributor to female subfertility in aged mammals. Currently, there are no effective interventions to ameliorate aged oocyte quality. Here we found that oocytes at metaphase I from the cumulus-oocyte complexes of aged mice showed reduced cortical F-actin and lower levels of mevalonate (MVA) pathway metabolites, including MVA, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate. We further showed that MVA supplementation improved FPP levels,...
Chuanming Liu

Digital exclusion and loneliness in older people: panel data analysis of three longitudinal cohort studies

1 month 1 week ago
CONCLUSION: Our findings indicate that a substantial proportion of older adults experience digital exclusion, particularly in China. Digital exclusion demonstrates a positive association with loneliness, suggesting that enhancing digital inclusion may serve as a critical strategy for alleviating loneliness and mitigating psychological distress in ageing populations.
Senda Zhong

Revisiting obesity thresholds for cardiovascular disease and mortality risk in Chinese adults: Age- and gender-specific insights

1 month 1 week ago
Current obesity classifications may not adequately reflect age- and gender-specific risks in diverse populations. In a prospective cohort study of 166,285 Chinese adults aged ≥40 years without prior cardiovascular disease (CVD) or cancer, we evaluate optimal thresholds of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) for predicting incident CVD and all-cause mortality. We observe monotonically increasing dose-response associations of BMI, WC, and WHR with CVD risk...
Xiaojing Jia

A redox switch in p21-CDK feedback during G2 phase controls the proliferation-cell cycle exit decision

1 month 1 week ago
Reactive oxygen species (ROS) influence cell proliferation and fate decisions by oxidizing cysteine residues (S-sulfenylation) of proteins, but specific targets and underlying regulatory mechanisms remain poorly defined. Here, we employ redox proteomics to identify cell-cycle-coordinated S-sulfenylation events and investigate their functional role in proliferation control. Although ROS levels rise during cell cycle progression, the overall oxidation of the proteome remains constant, with dynamic...
Julia Vorhauser

Integrative analysis of inhibition of advanced glycation end-products accumulation and prevention of aging muscle deterioration in animals and human models

1 month 1 week ago
CONCLUSIONS: Aerobic exercise mitigates AGEs-induced muscle deterioration through molecular and structural improvements. SAF and CML may serve as noninvasive biomarkers of functional decline in older adults. These findings highlight the potential of exercise to counteract sarcopenia associated with AGEs accumulation.
Moon Jin Lee

Early-life infectious disease exposure, the "hygiene hypothesis," and lifespan: Evidence from hookworm disease

1 month 1 week ago
Exposure to infectious disease in early life may have long-term ramifications for health and lifespan. However, reducing pathogen exposure may not be uniformly beneficial. The rise of modern sanitation and reduction of infectious diseases has been implicated in increasing levels of allergy and immune dysregulation: termed, the "hygiene hypothesis." This study leverages quasi-experimental variation from combining precampaign hookworm exposure with the Rockefeller Sanitary Commission's deworming...
Ralph Lawton

An exploration of basic human values in 38 million obituaries over 30 years

1 month 1 week ago
How societies remember the dead can reveal what people value in life. We analyzed 38 million obituaries from the United States to examine how personal values are encoded in individual and collective legacies. Using Schwartz's theory of basic human values, we found that tradition and benevolence dominated legacy reflections, while values like power and stimulation appeared less frequently. Major cultural events-the terrorist attacks of September 11th, the 2008 financial crisis, and the COVID-19...
David M Markowitz

Haematopoietic ageing in health and lifespan

1 month 1 week ago
Ageing of the haematopoietic system is characterized by phenotypic and functional impairments that are driven by alterations of haematopoietic stem cells and of the bone marrow niche. Haematopoietic stem cells are responsible for the production of all the different cell types that constitute the blood, and their maintenance and differentiation must be tightly regulated during the whole life of an organism. Exciting new data emphasize that central aspects of blood ageing, ranging from...
Rebecca Andersson

Chronic inflammation and cognitive frailty in older adults: A narrative review

1 month 1 week ago
Cognitive Frailty (CF) is a clinical syndrome characterized by the co-occurrence of physical frailty and cognitive impairment in the absence of dementia. This geriatric condition has emerged as a significant contributor to compromised health status and diminished quality of life among aging populations, yet its underlying pathological mechanisms remain incompletely elucidated. Chronic low-grade inflammation, recognized as a hallmark of biological aging, has been implicated in the pathogenesis of...
Qiqi Jiang
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