On the wake of metformin: Do anti-diabetic SGLT2 inhibitors exert anti-aging effects?

Scisciola, Lucia; Olivieri, Fabiola; Ambrosino, Concetta; Barbieri, Michelangela; Rizzo, Maria Rosaria; Paolisso, Giuseppe

doi:10.1016/j.arr.2023.102131

Cited by 11 publications

(2 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These drugs have a remarkable effect at the mitochondrial level, in many ways similar to that of CR and complementary to RAS‐blockade. As a result, their potential favorable effect on aging is highly probable (Hoong & Chua, 2021 ; Sanz et al., 2023 ; Scisciola et al., 2023 ). In any case, in order to qualify as candidates for use against human aging, this family of drugs still needs both proof of safety after prolonged use, and cost reduction.…”

Section: Summary and Discussionmentioning

confidence: 99%

Renin–angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?

de Cavanagh,

Inserra,

Ferder

2024

Physiological Reports

View full text Add to dashboard Cite

The renin–angiotensin system (RAS)—a classical blood pressure regulator—largely contributes to healthy organ development and function. Besides, RAS activation promotes age‐related changes and age‐associated diseases, which are attenuated/abolished by RAS‐blockade in several mammalian species. RAS‐blockers also increase rodent lifespan. In previous work, we discussed how RAS‐blockade downregulates mTOR and growth hormone/IGF‐1 signaling, and stimulates AMPK activity (together with klotho, sirtuin, and vitamin D‐receptor upregulation), and proposed that at least some of RAS‐blockade's aging benefits are mediated through regulation of these intermediaries and their signaling to mitochondria. Here, we included RAS‐blockade's impact on other aging regulatory pathways, that is, TGF‐ß, NF‐kB, PI3K, MAPK, PKC, Notch, and Wnt, all of which affect mitochondria. No direct evidence is available on RAS/RAS‐blockade‐aging regulatory pathway–mitochondria interactions. However, existing results allow to conjecture that RAS‐blockers neutralize mitochondrial dysfunction by acting on the discussed pathways. The reviewed evidence led us to propose that the foundation is laid for conducting clinical trials aimed at testing whether angiotensin‐converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)—even at subclinical doses—offer the possibility to live longer and in better health. As ACEi and ARB are low cost and well‐tolerated anti‐hypertension therapies in use for over 35 years, investigating their administration to attenuate/prevent aging effects seems simple to implement.

show abstract

Section: Summary and Discussionmentioning

confidence: 99%

Renin–angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?

de Cavanagh,

Inserra,

Ferder

2024

Physiological Reports

View full text Add to dashboard Cite

show abstract

“…Remarkably, SGLT2i may also positively impact the gut microbiome, further contributing to their potential anti-aging effects. This multifaceted action against inflammaging, a chronic low-grade inflammation linked to accelerated aging and age-related diseases, makes SGLT2i particularly interesting candidates for therapeutic repurposing[ 37 ]. However, robust clinical studies are crucial to validate the anti-aging potential of SGLT2i beyond their established role in diabetes management.…”

Section: Clinical Evidence: Cellular and Mitochondrial Protectionmentioning

confidence: 99%

Sodium-glucose cotransporter-2 inhibitors protect tissues via cellular and mitochondrial pathways: Experimental and clinical evidence

Sanz,

García Menéndez,

Inserra

et al. 2024

World J Exp Med

View full text Add to dashboard Cite

Mitochondrial dysfunction is a key driver of cardiovascular disease (CVD) in metabolic syndrome and diabetes. This dysfunction promotes the production of reactive oxygen species (ROS), which cause oxidative stress and inflammation. Angiotensin II, the main mediator of the renin-angiotensin-aldosterone system, also contributes to CVD by promoting ROS production. Reduced activity of sirtuins (SIRTs), a family of proteins that regulate cellular metabolism, also worsens oxidative stress. Reduction of energy production by mitochondria is a common feature of all metabolic disorders. High SIRT levels and 5’ adenosine monophosphate-activated protein kinase signaling stimulate hypoxia-inducible factor 1 beta, which promotes ketosis. Ketosis, in turn, increases autophagy and mitophagy, processes that clear cells of debris and protect against damage. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), a class of drugs used to treat type 2 diabetes, have a beneficial effect on these mechanisms. Randomized clinical trials have shown that SGLT2i improves cardiac function and reduces the rate of cardiovascular and renal events. SGLT2i also increase mitochondrial efficiency, reduce oxidative stress and inflammation, and strengthen tissues. These findings suggest that SGLT2i hold great potential for the treatment of CVD. Furthermore, they are proposed as anti-aging drugs; however, rigorous research is needed to validate these preliminary findings.

show abstract

Anti-aging interventions in geriatric mice: insights into the timing of treatment, benefits, and limitations

Malavolta

2024

GeroScience

View full text Add to dashboard Cite

On the wake of metformin: Do anti-diabetic SGLT2 inhibitors exert anti-aging effects?

Cited by 11 publications

References 73 publications

Renin–angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?

Renin–angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?

Sodium-glucose cotransporter-2 inhibitors protect tissues via cellular and mitochondrial pathways: Experimental and clinical evidence

Anti-aging interventions in geriatric mice: insights into the timing of treatment, benefits, and limitations

Contact Info

Product

Resources

About