“Unlocking longevity with GLP-1: A key to turn back the clock?”
DOI: doi:10.1016/j.maturitas.2024.108028
This sounds like a good study but I cannot find it on Research Gate or Anna’s Archive.
Does anyone have any other methods of finding studies?
Thank you. How did you get that?
My university library has access through licensing. If you sent the citation to your local library, plausibly, they could get you the article through ILL (Inter-library Loan). Not immediate gratification though.
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Thank you for the assistance. I find it sad that information is hidden behind paywalls when it could be spread further and generate more insights.
I’ve never considered my local library I might see if they have a service like that.
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Most likely doesn’t but can’t hurt to check. It’s university libraries that do. And yes I think it’s bullshit.
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I will email my local library right now and see if they can do this. I’m honestly just curious and it might be useful in the future.
I tried there as well but it wasn’t available there. I usually check Research Gate, and then Anna’s Archive, then Reddit. I have also directly emailed authors and sometimes they are kind enough to give it to me.
Parts I thought were good from the study:
Mitochondrial biogenesis and protection
Studies have explored the ability of GLP-1 to stimulate mitochondrial biogenesis in pancreatic β-cells, where mitochondrial function is critical for optimal insulin secretion. GLP-1 increases mitochondrial ATP production by driving greater utilisation of glucose and fatty acids and promotes the growth and fission of mitochondria, yielding more of these energy-generating organelles inside cells. It also protects mitochondria by reducing reactive oxygen species (ROS), stimulating mitochondrial dynamics, and shielding against mitochondrial damage.
Marco et al. examined the effect of a GLP-1 receptor agonist on mitochondrial function in patients with type 2 diabetes. Participants were divided into two groups, with or without GLP-1 treatment. Therapy with the agonist benefited polymorphonuclear neutrophils (PMNs) by lowering oxidative stress, boosting cellular energy production, and reducing inflammation and inter-cellular adhesion—findings that suggest therapeutic potential in disorders linked to inflammation and immune dysfunction.
Antiproliferative effects in hepatocellular carcinoma
Krause et al. investigated the antiproliferative actions of liraglutide (a GLP-1 analogue) in HepG2 hepatocellular carcinoma cells at concentrations of 10–20 µM for 24–48 h. Liraglutide induced cellular senescence and autophagy through increased TGF-β1 expression, indicating possible utility as a liver-cancer therapy [20].
Context-dependent effects on autophagy
GLP-1 can both activate and inhibit autophagy, depending on cell type and context. It triggers autophagy via AMPK/mTOR signalling, ROS reduction, and endoplasmic-reticulum stress mitigation, but it can also suppress autophagy through glucagon inhibition, mitochondrial protection, and other tissue-specific mechanisms.
Stem-cell modulation
The interaction between GLP-1 and stem-cell biology holds promise for regenerative medicine and age-related disease. GLP-1 enhances stem-cell proliferation, differentiation, migration, homing, mitochondrial function, and survival. In diabetic rats with nephropathy, Habib et al. showed that exenatide (a GLP-1 agonist) improved the renal-protective functions of adipose-derived mesenchymal stem cells after four weeks [23, 24].
Cardiovascular benefits
GLP-1 receptor agonists (GLP-1 RAs) were first adopted for glycaemic control but also improve classic cardiovascular-disease (CVD) risk factors such as dyslipidaemia, weight, and hypertension. Emerging evidence indicates that GLP-1 RAs may further enhance endothelial function, improve coronary perfusion under stress, and mitigate heart-failure progression.
Neurodegenerative disease mechanisms
Modulating GLP-1 activity can influence dopamine levels in Parkinson’s disease and amyloid-β aggregation in Alzheimer’s disease. GLP-1 RAs reduce oxidative stress, inflammation, and apoptosis, lessening cerebral infarct size and neurological deficits in stroke models. By enhancing synaptic plasticity, they may also improve diabetes- or obesity-related cognitive decline, bolstering memory and learning [29].
APP/PS1 mouse data
In 14-month-old APP/PS1 mice, liraglutide (25 nmol kg⁻¹ i.p. for two months) improved spatial memory, increased neuronal progenitor cells in the dentate gyrus, reduced inflammation and amyloid-plaque load, elevated cortical and hippocampal synapse counts, and markedly enhanced long-term potentiation.
Cancer-risk meta-analysis
Wang et al. compared cancer incidence in 619,340 metformin-treated patients versus 64,230 GLP-1 RA users over five years. GLP-1 RA exposure was associated with lower risks of prostate, lung, and colon cancers but a higher risk of thyroid cancer. Longer exposure further reduced prostate, colon, and lung cancer risk [37]. Because most data are observational, randomised trials are needed to confirm causality.
Muscle-atrophy studies
Using C2C12 myoblasts in vitro and rat models of freeze injury or denervation in vivo, liraglutide significantly protected against muscle atrophy, improving myogenic capacity and overall muscle function [39].
Osteoarthritis model
Meurot et al. found that intra-articular liraglutide (5–20 µg) reduced cartilage catabolism and pain in a mouse model of osteoarthritis. At 20 µg, its effects matched those of 20 µg dexamethasone and surpassed saline controls, also improving synovitis scores [40].
Age-related macular degeneration (AMD)
In preclinical AMD models, GLP-1 RAs reduce inflammation, provide neuroprotection, and enhance retinal blood flow. Seppa et al. reported that six months of liraglutide treatment lowered neuroinflammation, alleviated AMD-like symptoms, and protected retinal ganglion cells in aged rats [41].
CNS distribution and cognition
GLP-1 receptors are widely expressed in the brain and their agonists cross the blood-brain barrier [57, 58]. In a 12-week trial of 50 type 2-diabetes patients (NCT03707171), liraglutide improved scores across all cognitive domains—especially memory and attention—and increased activation of the dorsolateral prefrontal and orbitofrontal cortices, independently of changes in BMI, blood pressure, or glycaemic control [59].
Synaptic plasticity and signalling
Liraglutide prevented high-fat-diet-induced deficits in hippocampal synaptic plasticity in an Alzheimer’s mouse model [75]. GLP-1 receptor deletion reduced long-term potentiation (LTP) in CA1 neurons [76]. GLP-1 RAs up-regulated mTOR and Ntrk2 expression in the hippocampus, crucial for LTP and synaptic function.
DNA repair and senescence
GLP-1 R signalling stimulates apurinic/apyrimidinic endonuclease-1 (APE1) to enhance DNA repair [79], reduces oxidative-stress-driven DNA damage, and counters H₂O₂-induced senescence while boosting antioxidant defences [80].
Cardiomyocyte and mitochondrial protection
Liraglutide shields cardiomyocytes from IL-1β-induced mitochondrial dysfunction, and GLP-1 R activation suppresses methylglyoxal-driven mitochondrial injury in H9c2 cardiomyoblasts [84].
Key survival pathways
GLP-1 acts through the PI3K/Akt/mTOR pathway to prevent cell death [86]; liraglutide protects β-cells from apoptosis via AMPK/mTOR [87]; and the DPP4–GLP-1 axis modulates cellular senescence through AMPK/SIRT1/FOXO3a [90].