Longevity

7 Compounds Shown To Extend Lifespan In Mice

Posted on 7 October 2020

Drugs that can significantly extend lifespan are a reality – at least, in animal models. The National Institute on Aging Interventions Testing Program (ITP) is a multi-institutional study investigating treatments with the potential to extend lifespan and delay disease in mice. Here are the seven compounds so far tested by the ITP that have been shown to extend rodent lifespan, and could potentially pave the way for lifespan extension in humans.

1: Aspirin

Aspirin and your heart: Many questions, some answers - Harvard Health

One drug on this list that you are almost certain to be familiar with is aspirin. A highly versatile drug, aspirin is a painkiller with anti-inflammatory, anti-cancer, cardioprotective and, it appears, lifespan – extending properties. Aspirin extends the median lifespan of male mice by 8%, though this effect doesn’t seem to extend to females – possibly due to gender differences in the way the drug is metabolised.

2: Rapamycin

Figure 1.

If you follow longevity research, there’s a good chance you’ve heard of the immunosuppressant drug rapamycin. Rapamycin inhibits mTOR (mammalian target of rapamycin), a protein that is thought to be a central regulator of the ageing process. Feeding rapamycin to old mice (600 days of age) led to a lifespan increase of 14% for females and 9% for males.

3: 17-α-Estradiol

Estradiol | Hormone Health Network

17-α-estradiol is a weak form of the female sex hormone oestrogen, with around 100-fold lower potency than the predominant oestrogen, 17-β-estradiol. In animals, it seems to protect the brain against vascular and neurodegenerative diseases, and when given to male mice, can extend their median lifespan by 12% (though maximum lifespan is unaffected).

4: Acarbose

Acarbose is a drug used to treat type II diabetes. It works by inhibiting enzymes that break down carbohydrates, thereby reducing glucose absorption and lowering blood sugar levels. Since calorie restriction has been shown to extend lifespan in animals, researchers investigated whether acarbose could also produce this effect. Sure enough, acarbose increased median and maximum lifespan by 22% and 11% respectively in male mice. In female mice the effect was weaker, with an 11% increase in median lifespan and a 9% increase in maximum lifespan.

5: Nordihydroguaiaretic Acid

Creosote - Desert Horizon Nursery

Nordihydroguaiaretic acid (NDGA) is an andtioxidant compound found in the creosote bush, a plant that has been subject to some controversy. Once used as a food preservative, it was banned following reports of toxicity in the 1960s. Despite this, NDGA appears to have lifespan extending effects in animals, increasing mean lifspan by 50% in mosquitos and median lifespan by 12% in male mice.

6: Protandim

Protandim is a dietary supplement containing a patented mix of five herbal ingredients. Protandim is a controversial product, as it has been marketed with a number of unsupported (and illegal) claims that it can help cure diseases like cancer and diabetes. The botanical extracts in question are activators of Nrf2, a protein that controls the production of antioxidants. Since oxidative stress in thought to be a key driver of the ageing process, researchers have studied the effects of protandim on lifespan, and it does appear that this supplement can increase median lifespan in male mice by 7%.

7: Canagliflozin

What Are the Side Effects of Invokana (Canagliflozin)?

We mentioned how acarbose might increase lifespan by interfering with carbohydrate breakdown. Canagliflozin (cana) is another antidiabetic drug that may extend lifespan in a similar way. Instead of inhibiting the breakdown of carbs, canagliflozin blocks the absorption of glucose in the intestines and kidneys by inhibiting the glucose trasporter SGLT2. In male mice, cana extended median lifespan by 14% and increased the survival age of the longest-living mice by 9%.


It is much easier to study lifespan extension in animals with short lifespans than in humans, and many of the above lifespan-extending effects will remain limited to animal studies. However, as we discover more compounds with the potential to extend lifespan, we also improve our understanding of the fundamentals of ageing and how we might be able to fight it.


References

Dietary nordihydroguaiaretic acid increases the life span of the mosquito: DOI: 10.3181/00379727-183-42389

Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer: doi: 10.1111/acel.12496

Canagliflozin extends lifespan in genetically heterogeneous male but not female mice: 10.1172/jci.insight.140019

Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice: doi: 10.1111/j.1474-9726.2008.00414.x

Rapamycin fed late in life extends lifespan in genetically heterogeneous mice: doi: 10.1038/nature08221

Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males: doi: 10.1111/acel.12170

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