Oncotarget: The goal of geroscience is life extension

Dr. Mikhail V. Blagosklonny, M.D., Ph.D., Adjunct Professor, at Roswell Park Comprehensive Cancer Center, published published "The goal of geroscience is life extension" which was selected as the Featured Cover Paper for Volume 12 Issue 3 and reported that although numerous drugs seemingly extend healthspan in mice, only a few extend lifespan in mice and only one does it consistently. Some of them, alone or in combination, can be used in humans, without further clinical trials.

Dr. Mikhail V. Blagosklonny from Roswell Park said, "Although we do not know everything about aging, we now know enough to start its pharmacologic suppression using clinically approved drugs."

Published in 2010, these opening words of the paper entitled "Increasing healthy lifespan by suppressing aging in our lifetime: preliminary proposal" are still relevant today.

Hyperfunction of these signaling pathways directly drive all age-related diseases, which are manifestations of aging. We just need clinically available inhibitors of these signaling pathways to extend both healthspan and lifespan, by slowing aging.

A mere extension of healthspan is not enough: drugs that fail to extend lifespan in mice will fail to extend lifespan in humans, if used as a monotherapy.

Figure 1: Extension of healthspan extends lifespan. (A) Healthspan is the period of life without diseases. Diseases (black color) terminate lifespan. Subclinical aging (white color) progresses to pre-diseases (gray) and diseases (black). X axis: age. Y axis: loss of health (a sum of diseases) in log scale. (B) Longevity intervention slows aging and extends healthspan, automatically extending lifespan. (C) Unrealistic scenario "Healthspan without lifespan". Compressed morbidity (black). Either diseases progress instantly, or animals die from "health" rather than from diseases.

Yet, in rational combinations with life-extending drugs, "healthspan-only" drugs may extend lifespan further.

In this Oncotarget publication, Dr. Blagosklonny reviews drugs that extend lifespan and healthspan in mammals, in contrast to those that may affect only healthspan without lifespan, and discusses how to proceed with clinical application of lifespan-extending drugs.

Blagosklonny concluded in their Oncotarget Research Perspective, "If we want to live longer, we have no choice, but to use drugs such as rapamycin, which extends life in short-lived mammals and is approved for humans use. After all, humans are mammals, and there is no reason to think that they will not work in humans."

Please note: This review is intended for a professional audience. This article does not represent medical advice or recommendations to patients. The media should exercise caution and seek expert medical advice for interpretation, when referring to this article. Medical doctors interested in this topic may e-mail the author at Blagosklonny@rapalogs.com or follow on Twitter @Blagosklonny

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DOI - https://doi.org/10.18632/oncotarget.27882

Full text - https://www.oncotarget.com/article/27882/text/

Correspondence to - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com

Keywords - aging, longevity, rapamycin, mTOR, metformin

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