Aging & Longevity

Cellular senescence by loss of Men1 in osteoblasts is critical for age-related osteoporosis

8 months ago
Recent evidence suggests an association between age-related osteoporosis and cellular senescence in the bone; however, the specific bone cells that play a critical role in age-related osteoporosis and the mechanism remain unknown. Results revealed that age-related osteoporosis is characterized by the loss of osteoblast Men1. Osteoblast-specific inducible knockout of Men1 caused structural changes in the mice bones, matching the phenotypes in patients with age-related osteoporosis....
Yuichiro Ukon

Lens capsule advanced glycation end products induce senescence in epithelial cells: Implications for secondary cataracts

8 months ago
Posterior capsule opacification (PCO) is a common complication after cataract surgery. Residual lens epithelial cells (LECs) on the anterior lens capsule, after cataract surgery, migrate to the posterior lens capsule and undergo transdifferentiation into myofibroblast-like cells. Those cells synthesize excessive amounts of extracellular matrix and contribute to fibrosis during PCO. Cellular senescence, a phenomenon that increases with aging, has been implicated in several fibrotic diseases....
Grace Cooksley

β-synuclein regulates the phase transitions and amyloid conversion of α-synuclein

8 months ago
Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates...
Xi Li

Dietary restriction impacts health and lifespan of genetically diverse mice

8 months ago
Caloric restriction extends healthy lifespan in multiple species¹. Intermittent fasting, an alternative form of dietary restriction, is potentially more sustainable in humans, but its effectiveness remains largely unexplored^(2-8). Identifying the most efficacious forms of dietary restriction is key for developing interventions to improve human health and longevity⁹. Here we performed an extensive assessment of graded levels of caloric restriction (20% and 40%) and intermittent fasting (1 and 2...
Andrea Di Francesco

Spatial and functional separation of mTORC1 signalling in response to different amino acid sources

8 months ago
Amino acid (AA) availability is a robust determinant of cell growth through controlling mechanistic/mammalian target of rapamycin complex 1 (mTORC1) activity. According to the predominant model in the field, AA sufficiency drives the recruitment and activation of mTORC1 on the lysosomal surface by the heterodimeric Rag GTPases, from where it coordinates the majority of cellular processes. Importantly, however, the teleonomy of the proposed lysosomal regulation of mTORC1 and where mTORC1 acts on...
Stephanie A Fernandes

Hippocampal rejuvenation by a single intracerebral injection of one-carbon metabolites in C57BL6 old wild-type mice

8 months ago
The Izpisua-Belmonte group identified a cocktail of metabolites that promote partial reprogramming in cultured muscle cells. We tested the effect of brain injection of these metabolites in the dentate gyrus of aged wild-type mice. The dentate gyrus is a brain region essential for memory function and is extremely vulnerable to aging. A single injection of the cocktail containing four compounds (putrescine, glycine, methionine and threonine) partially reversed brain aging phenotypes and epigenetic...
Alejandro Antón-Fernández

CaMKIIalpha-TARPgamma8 signaling mediates hippocampal synaptic impairment in aging

8 months ago
Aging-related decline in memory and synaptic function are associated with the dysregulation of calcium homeostasis, attributed to the overexpression of voltage-gated calcium channels (VGCC). The membrane insertion of AMPAR governed by the AMPAR auxiliary proteins is essential for synaptic transmission and plasticity (LTP). In this study, we demonstrated the hippocampal expression of the transmembrane AMPAR regulatory proteins γ-8 (TARPγ8) was reduced in aged mice along with the reduced CaMKIIα...
Zhao JianHua

The Combined Effect of Green Tea, Saffron, Resveratrol, and Citicoline against Neurodegeneration Induced by Oxidative Stress in an <em>In Vitro</em> Model of Cognitive Decline

8 months ago
During ageing, the brain is vulnerable to a growing imbalance of the antioxidant defence system, resulting in increased oxidative stress. This condition may be mainly responsible for cognitive decline, resulting in synaptic transmission disruptions and the onset of neuronal dysfunction. In this context, developing efficient preventive and therapeutic strategies against increased oxidative stress and decreased antioxidant defence mechanisms should be considered a public health priority to promote...
Simone Mulè

Brain activation in older adults with hypertension and normotension during standing balance task: an fNIRS study

8 months ago
CONCLUSION: The standing balance function of older adults with HT does not appear to be worse based on COP parameters than those of older adults with NT. This study revealed that the changes in the central cortex related to standing balance appear to be more indicative of balance control deficits in older adults with HT than changes in peripheral COP parameters, suggesting the importance of the early evaluation of cortical activation in older adults with HT at risk of falls.
Weichao Fan

A germline-to-soma signal triggers an age-related decline of mitochondrial stress response

8 months ago
The abilities of an organism to cope with extrinsic stresses and activate cellular stress responses decline during aging. The signals that modulate stress responses in aged animals remain to be elucidated. Here, we discover that feeding Caenorhabditis elegans (C. elegans) embryo lysates to adult worms enabled the animals to activate the mitochondrial unfolded protein response (UPR^(mt)) upon mitochondrial perturbations. This discovery led to subsequent investigations that unveil a hedgehog-like...
Liankui Zhou

The brain-body energy conservation model of aging

8 months ago
Aging involves seemingly paradoxical changes in energy metabolism. Molecular damage accumulation increases cellular energy expenditure, yet whole-body energy expenditure remains stable or decreases with age. We resolve this apparent contradiction by positioning the brain as the mediator and broker in the organismal energy economy. As somatic tissues accumulate damage over time, costly intracellular stress responses are activated, causing aging or senescent cells to secrete cytokines that convey...
Evan D Shaulson

Skeletal stem and progenitor cells in bone physiology, ageing and disease

8 months ago
Skeletal stem cells (SSCs) and related progenitors with osteogenic potential, collectively termed skeletal stem and/or progenitor cells (SSPCs), are crucial for providing osteoblasts for bone formation during homeostatic tissue turnover and fracture repair. Besides mediating normal bone physiology, they also have important roles in various metabolic bone diseases, including osteoporosis. SSPCs are of tremendous interest because they represent prime future targets for osteoanabolic therapies and...
Seppe Melis

Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25-57% elevation in risk

8 months ago
The incidence of colorectal cancer (CRC) has been steadily rising, and obesity has been identified as a significant risk factor. Numerous studies suggest a strong correlation between excess body weight and increased risk of CRC, but comprehensive quantification through pooled analysis remains limited. This study aims to systematically review and meta-analyze the existing literature to evaluate the association between obesity and CRC risk, considering variations across sex and study designs. A...
Zoltan Ungvari

Hyperactive mTORC1/4EBP1 signaling dysregulates proteostasis and accelerates cardiac aging

8 months ago
The mechanistic target of rapamycin complex 1 (mTORC1) has a major impact on aging by regulation of proteostasis. It is well established that mTORC1 signaling is hyperactivated with aging and age-related diseases. Previous studies have shown that partial inhibition of mTOR signaling by rapamycin reverses age-related deteriorations in cardiac function and structure in old mice. However, the downstream signaling pathways involved in this protection against cardiac aging have not been established....
Weronika Zarzycka

GWAS of multiple neuropathology endophenotypes identifies new risk loci and provides insights into the genetic risk of dementia

8 months ago
Genome-wide association studies (GWAS) have identified >80 Alzheimer's disease and related dementias (ADRD)-associated genetic loci. However, the clinical outcomes used in most previous studies belie the complex nature of underlying neuropathologies. Here we performed GWAS on 11 ADRD-related neuropathology endophenotypes with participants drawn from the following three sources: the National Alzheimer's Coordinating Center, the Religious Orders Study and Rush Memory and Aging Project, and the...
Lincoln M P Shade
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