Γ—

Chloroquine Increases Lifespan in Male Mice

Doubling or quadrupling the dose, however, increases the toxicity.

Share







Lab mouse in handLab mouse in hand

Researchers publishing in Aging have found that the anti-malarial drug chloroquine increases lifespan in male NRMI mice. The NRMI, like the Black 6, is a standard breed widely used in research, and these mice were not directly genetically modified.

To do this, we need your support. Your charitable contribution tranforms into rejuvenation research, news, shows, and more. Will you help?

Substantial positive lifespan effects

We have previously reported a study showing that choloroquine increases longevity in rats, and this study’s results were similar. However, these researchers did not expect such results here: the purpose of this study was to rule out a potentially negative effect on lifespan rather than to find a positive one.

A 50 mg/kg dose of chloroquine was administered at day 500 of lifespan. While the mortality rates of the treatment and control groups began similarly, there was a long period in which the treated mice stopped dying. Slightly before 700 days after the mice were born, all of the untreated group had died while half of the treatment group was still alive; the last treated mouse died a hundred days later.

Food intake did not decrease in the treated group, although liquid intake and body weight were both slightly decreased.

Toxicity

This study showed that chloroquine can be toxic to the liver. Although the 50 mg/kg dose did not lead to significant pathological changes, the 100 mg/kg and 200/kg doses led to hydropic degeneration and even hepatocyte necrosis, the death of functional liver cells.

The heart results, as expected, also showed signs of toxicity, although the toxicity was not significant until higher doses. However, even the 50 mg/kg dose was associated with mild interstitial edema and a loss of striations, two signs of muscle damage, and these results only worsened with increasing doses.

This toxicity was accompanied by a decrease in proteostasis-related activity. The proteosome, which is responsible for recycling unwanted proteins, was significantly downregulated in the liver at 100 mg/kg and in the heart at 200 mg/kg.

Of mice and autophagy

Previous research has shown that chloroquine significantly interferes with the fundamental mechanisms behind autophagy, the process by which cells clear out unwanted components [1]. Autophagy is normally seen as a good thing, as it removes waste; however, the self-cannibalism of cells can obviously have a harmful aspect as well.

The researchers hypothesize that the lifespan results, which fly in the face of the toxicity results, are due to the modulation of autophagy, a reduction in proteostasis mechanisms, and an alteration in the way the cells process glycogen. However, these are only hypotheses; further research is needed to confirm them.

Conclusion

This study adds to a body of conflicting and contradictory research, and while it answers some questions, many others only still have hypothetical answers. Things like autophagy and even protein recycling are not always good nor bad. “The dose makes the poison” is well known in medicine, and it has been once again shown here.

This was a rodent study, and chloroquine, by itself, is unlikely to move the needle much on human longevity. However, what this study does tell us, and further studies will hopefully elucidate in detail, is that the low-level biology of cellular aging can be successfully interfered with.

There are two broader, critical questions that are downstream of this line of research. The first is the inverse of this study: whether or not autophagy-enhancing interventions that increase lifespan have downsides that can be removed to enhance their effectiveness. The second is whether or not these sorts of interventions are any more effective than basic lifestyle choices in lengthening human lifespan.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. We are committed to responsible journalism, free from commercial or political influence, that allows you to make informed decisions about your future health.

All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future. You can support us by making a donation or in other ways at no cost to you.

Study: Waist-to-Hip Ratio Predicts Mortality Better Than BMI

A new study suggests that waist-to-hip ratio (WHR) has a more linear correlation with all-cause mortality than either body mass...

Restoring Heart Regeneration With a Metabolic Switch

In a recent article in Nature, researchers have restored cardiac regeneration to adult mice by disabling fatty acid oxidation, discovering...

Human Clinical Trials of NMN for Safety and Effectiveness

In a recent paper, researchers reviewed the literature for human clinical trials that address NMN's safety and anti-aging effects [1]....

Lifespan News – Elon Musk and the Living Forever Curse

On this episode of Lifespan News, Ryan O'Shea ruminates on Elon Musk's statement on living forever being a curse rather...

Literature

[1] Mauthe, M., Orhon, I., Rocchi, C., Zhou, X., Luhr, M., Hijlkema, K. J., … & Reggiori, F. (2018). Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy, 14(8), 1435-1455.

About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called β€œreal life.” Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.
No Comments
Write a comment:

*

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.