Novel strategies for anti-aging drug discovery

ABSTRACT

Introduction: Scientific achievements in the last few decades, leading to effective therapeutic interventions, have dramatically improved human life expectancy. Consequently, aging has become a significant problem and represents the major risk factor for most human pathologies including diabetes, cardiovascular diseases, neurological disorders, and cancer. Scientific discoveries over the past two decades have been instrumental in dissecting molecular mechanism(s) which play important roles in determining longevity. The same understanding has also led to the acknowledgement of the plurality of ‘causes’ which act either alone or in combination to create the condition which can be defined as ‘aging’.

Areas covered: Over the years, several concepts have been put forward for the development of a viable anti-aging regimen. In this review, the authors extensively review anti aging interventions based on caloric restriction, activation of telomerase, autophagy inducers, senolytic therapeutics, plasma membrane redox system (PMRS) activators, epigenetic modulators, and stem cell therapies.

Expert opinion: Based upon our current understanding, one of the most promising approaches for a successful anti-aging strategy includes the activation of adenosine monophosphate dependent protein kinase (AMPK). Another strategy may involve activation of PMRS. Future research efforts are likely to focus on nutrient and energy sensing molecular pathways which include mTOR, IGF-1, AMPK and the sirtuins.

KEYWORDS:

• Anti-aging
• caloric restriction
• telomerase activation
• autophagy inducers
• PMRS activators
• senolytic therapeutics
• epigenetic modulators

Article highlights

• Recent years have witnessed an array of strategies which have been experimented under the ‘anti-aging’ category.

• Caloric restriction is the most promising anti-aging intervention although its implementation in humans is difficult. Caloric restriction mimetics show promise.

• Chemical Inhibitors of glycolysis, mTOR and GH and activators of AMPK and Sirtuins are reported to have significant life extending effects.

• Telomerase based therapies also report increase in healthspan without onset of cancer.

• Activation of autophagy may be an effective anti-aging strategy.

• Activation of the plasma membrane redox system is a potential therapeutic target which may effectively combat age-related oxidative stress.

• Senolytic drugs and pharmacological modulation of epigenetic changes are also encouraging approaches for the development future anti-aging drugs.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by a research grant to SIR from SERB-DST, Govt of India (EMR/2016/006470). The Department of Biochemistry, University of Allahabad is supported by FIST Grant from DST, New Delhi and SAP-DRS Grant from University Grants Commission, India.