Longevity

Study Shows Chloroquine Extends Lifespan and Rejuvenates Multiple Organs

Chinese researchers show that the anti-malaria drug chloroquine moderately extends the lifespan and rejuvenates the organs of elderly rats.

By Yedida Bogachkov, Ph.D.

Key Points:

  • Chloroquine revitalizes prematurely aged human stem cells.
  • Treatment with chloroquine prolongs rat lifespan and reduces age-related damage to multiple organs. 
  • Age-related genetic changes are reversed with chloroquine treatment.

Chloroquine has long been used to treat malaria and other viral infections, which may be why former President Donald Trump once promoted chloroquine for the treatment of COVID-19. Still, many recent studies show that chloroquine is involved in regulating cellular senescence, the process by which cells age. And now a new study, out of Beijing, shows that low doses of chloroquine may have anti-aging effects that can extend one’s lifespan.

The study was published in Protein and Cell and focused on the anti-aging benefits of low-dose chloroquine in prematurely aged human cells and naturally aged rats. Chloroquine treatment renewed the prematurely aged cells, allowing them to be less senescent and more proliferative. Similar treatment prolonged the lifespan of old rats, repressed their inflammation, and prevented age-related damage to multiple organs. The treatment also helped to reduce age-related changes at the gene level.

“Our data provide a valuable resource for investigating the impact of [chloroquine] on multiple aged tissues, which may facilitate the development of clinical applications that mitigate age-related changes in the elderly,” the researchers wrote.

Chloroquine Revitalizes Human Stem Cells 

As we age, our stem cells lose their ability to propagate (proliferate), partially due to an increase in senescent cells — cells that contribute to the aging process. To study the effect of chloroquine on aging, Li and colleagues examined stem cells from patients with Werner syndrome, a rare disorder that causes rapid aging. Like normally aged stem cells, Werner syndrome stem cells exhibit reduced propagation and increased levels of senescent cells. Results showedthat treatment with chloroquine reduced senescent cells and revitalized the proliferative capacity of these aged stem cells.

chloroquine treated cells result in fewer senescent cells
(Li et al., 2022 | Protein Cell) Chloroquine Revitalizes Aged Stem Cells. C) Aged stem cells treated with chloroquine (CQ) have fewer senescent cells (SA-β-gal) and D) proliferate (Ki67) more than untreated stem cells (Ctrl).

Chloroquine Prolongs Lifespan and Reduces Signs of Aging

To study the whole-body and longevity effects of chloroquine on aging, Li and colleagues treated 24-month-old rats (approximately 60 years old in human years) with 0.1 mg/kg of chloroquine orally twice a week for five months. As a result, chloroquine treatment increased the maximum lifespan of the rats  by 13%. Furthermore, markers of inflammation, a hallmark of aging, were reduced with chloroquine treatment. 

As we age, our organs accumulate damage and begin to scar (fibrosis), making them work less efficiently. Li and colleagues found that chloroquine treatment reduced fibrosis in many tissues, including the kidney, lungs, and small intestine. Senescence, however, seemed unaffected, except for in lung tissue where senescent cells tended to be reduced. These findings suggest that chloroquine mitigates age-related organ damage, but not by reducing senescence. 

chloroquine extends lifespan
(Li et al., 2022 | Protein Cell) Chloroquine Prolongs Lifespan and Reduces Age-Related Organ Damage. Old rats treated with chloroquine (O-CQ) live longer than untreated old rats (O-Ctrl). Small intestine tissue shows decreased fibrosis in O-CQ compared to O-Ctrl. However, young mice (Y-Ctrl) still have less fibrosis than O-CQ.

With aging comes changes in our gene activation patterns, which underlie the aging process. Li and colleagues found that age-related changes in gene activation were reversed by chloroquine treatment in the kidney, small intestine, and liver of old rats. Genes associated with pro-inflammatory processes and the aging process were among those reduced with chloroquine treatment. However, the heart exhibited an increase in pro-aging genes , indicating that perhaps even a low dose of chloroquinecould harm the heart, which has been seen when chloroquine is used to treat other conditions.

Chloroquine is a Viable Anti-Aging Agent

Despite some reservations of chloroquine treatment, particularly its effects on the heart (although these were not physiological), this study does show longevity effects at low doses, as well as reductions in fibrosis and alleviation of stem cell senescence. A previous study had shown that chloroquine also increases the lifespan of worms and a premature aging mouse model.

Chloroquine’s ability to inhibit inflammation and reduce fibrosis may be at the heart of its anti-aging properties. As the population’s average age increases, the need for good anti-aging medications that work on tissues at a genetic level with limited side effects is crucial. Chloroquine may fit that role if patients’ heart function can be well monitored.

Model & Dosage

Model: Sprague Dawley rats

Dosage (oral): 0.1 mg/kg chloroquine

Source

Li W, Zou Z, Cai Y, Yang K, Wang S, Liu Z, Geng L, Chu Q, Ji Z, Chan P, Liu GH, Song M, Qu J, Zhang W. Low-dose chloroquine treatment extends the lifespan of aged rats. Protein Cell. 2022 Jun;13(6):454-461. doi: 10.1007/s13238-021-00903-1. PMID: 35023015; PMCID: PMC9095792.

References

Qian, M., Liu, Z., Peng, L., Tang, X., Meng, F., Ao, Y., Zhou, M., Wang, M., Cao, X., Qin, B., et al. (2018). Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria. eLife 7.

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