Investigational drugs and nutrients for human longevity. Recent clinical trials registered in ClinicalTrials.gov and clinicaltrialsregister.eu

ABSTRACT

Introduction:

Several pharmacological drugs have shown proof of concept for longevity in animal models. I aimed to identify and review those longevity drug candidates that are undergoing clinical trials.

Areas covered:

Recent (post-2017) longevity clinical trials were found in US and EU clinical trial registries. Longevity drug candidates are the antidiabetic drugs metformin and acarbose, and the immunosuppressant rapamycin. These medicinal drugs are tested on biochemical and clinical markers of aging. In addition, vitamin D supplementation is being investigated in two mega-trials (sample size> 5000) for its efficacy in reducing all-cause mortality.

Expert opinion:

Anti-aging effects of longevity drug candidates suggest, but do not demonstrate that they prolong life. The two megatrials with vitamin D supplementation make it possible to detect differences in life expectancy between vitamin D and placebo. Therefore, a protocol similar to that for vitamin D could be used to demonstrate pro-longevity effects of metformin, acarbose, and rapamycin.

KEYWORDS:

• Acarbose
• aging
• clinical trials
• longevity
• metformin
• omega-3
• rapamycin
• vitamin D

Article highlights

• Three medicinal drugs - the antidiabetics metformin and acarbose and the immunosuppressant rapamycin–have demonstrated proof of concept for longevity in animal models. Clinical trials have recently been initiated with these longevity drug candidates.

• Metformin regulates gene expression of metabolic and nonmetabolic pathways linked to aging. Acarbose and rapamycin are tested on biochemical or clinical markers of aging. Anti-aging effects of longevity drug candidates suggest, but do not demonstrate that they prolong life.

• At the moment, a direct evaluation of the effect of drugs on human longevity does not seem feasible. Two megatrials (sample size >5000) are investigating the efficacy of vitamin D supplementation in reducing all-cause mortality (increasing survival). A similar protocol could be used to investigate whether metformin, acarbose, and rapamycin prolong life.

• The clear advantage of using longevity as a criterion for clinical efficacy is that it is a major, well-defined, and measurable concept. Current short-term clinical trials on aging parameters can help decide whether or not to launch all-cause mortality trials with longevity drug candidates.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Declaration of interest

RP Garay is a member of a non-profit association for therapeutic innovation (Craven, Villemoisson-sur-Orge, France). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper is not funded.