A review from researchers at King's College London focuses on the anti-ageing effects of a group of drugs called sodium-glucose cotransporter 2 inhibitors (SGLT2i), which are already approved as a treatment for diabetes.
Diabetes accelerates the ageing process and shortens life expectancy of people with this condition by up to 10 years. SGLT2i are emerging as a family of drugs with a much broader therapeutic scope including organs protection in diabetes, and cardiovascular renal diseases and now seem to appear as a new anti-ageing treatment.
SGLT2i have been shown to reduce the progression of kidney disease and the risk of hospitalisation for heart failure, both in patients with and without diabetes. Using data from several clinical trials, the authors estimate that SGLT2i are associated with an 18-25% relative reduction in cardiovascular death or hospitalisation with heart failure compared to placebo. This is due to various mechanisms including blood pressure, glucose levels, and insulin levels lowering effects.
The article from Dr Maltese and his colleagues, published in Trends in Endocrinology and Metabolism, expands our understanding on SGLT2i by describing their anti-ageing effects on vessels and body organs in animals and cultured cells.
Work produced by other scientists has indicated that SGLT2i can increase lifespan of mice by up to 14% and favour longevity. In the review article, the authors emphasise that SGLT2i induce molecular mechanisms shared by other agents like metformin and rapamycin, which are also being investigated as potential anti-ageing therapies.
SGLT-2 inhibitors are unique medications which started their journey as a treatment for diabetes but are now recommended for treatment of heart failure and kidney disease in people with and without diabetes. This class of medications provide novel mechanisms of benefit and have the potential to delay as well as prevent accelerated ageing which is a key feature of many long-term chronic conditions.– Senior author Dr Janaka Karalliedde
Alongside a description of SGLT2i, the authors highlight their relationship with the kidney-derived anti-ageing hormone Klotho. Previous studies using animal models demonstrated that the deletion of Klotho gene is associated with pre-mature ageing, whereas its over-expression is associated with 30% survival increase. The circulating level of Klotho declines with ageing and in pathologies such as diabetes, hypertension, kidney diseases and cancer.
Named after the daughter of Zeus who was thought to "spin the thread of life" promoting longevity in Greek mythology, Klotho has become an important focus of research aimed to identify substances that could stimulate its circulating levels. Based on emerging evidence, Dr Maltese and his colleagues propose Klotho as an intermediary of SGLT2i in vessels and organs protection against ageing.
What makes SGLT2i unique in the panorama of putative pro-longevity agents is their already extensively proved efficacy in reducing cardiovascular renal morbidity and all-cause mortality in large clinical trials. We need longer human studies to explore the effects of SGLT2i on markers of ageing and their potential to reverse ageing related disease and dysfunction.– Dr Giuseppe Maltese, lead author and Clinical Lecturer in Endocrinology and Diabetes
The authors conclude that SGLT2i hold the promise to be a therapy for a range of age-related diseases beyond its current role in diabetes and cardiovascular medicine. Further research is needed to confirm that Klotho is a key mediator of the the anti-ageing effects of SGLT2i.
