Monthly Archives: June 2012

Exception to Several Theories of Aging – Why Do Naked Mole Rats Live So Long?

Naked mole-rats (Heterocephalus glaber) are rodents found in the hot tropical regions of the Horn of Africa. When he first described a naked mole-rat in 1842, the famous German naturalist Eduard Rüppell suspected he had encountered a diseased specimen—because the animal had no fur and permanently protruding teeth. Only after several more specimens had been collected did it become apparent that their weird appearance, variously described as resembling saber-toothed sausages or miniature walruses, was normal.
Naked mole-rats live in a maze of underground tunnels that may extend more than a mile in length and as deep as 8 feet beneath the soil surface. Their burrows contain both nest chambers, tended by sterile worker animals, and several toilets, which the animals use religiously to avoid contamination of their living space. To locate the roots, tubers, and small onion-like bulbs they eat, mole-rats must dig through the soil, expanding their tunnels using their chisel-like, ever-growing incisor teeth. They occasionally make an opening to the outside world to kick excavated soil to the surface, where it forms small volcano-shaped mounds—the only aboveground signs of the vast colonies below. Given this strictly subterranean existence, it is not surprising that naked mole-rats have evolved a set of characteristics highly suited to life in dark, dank burrows.

This is how the naked mole rat’s colony looks like. This excellent review in The Scientist by Thomas Park and Rochelle Buffenstein illustrates the complicated lives of these outstanding hairless animals: how they live under the ground in Africa, how they have the breeding Queen and worker-animals (just like the honey bees), how they don’t feel certain kinds of pain, how they are resistant to the lack of oxygen and toxic amounts of carbon dioxide in the air. But the coolest thing about the naked mole rats is that they basically live 9 times more than “they should”:

Although naked mole-rats are the size of a mouse, weighing only about 35–65 grams, in captivity these rodents live 9 times longer. With a recorded maximum lifespan of 32 years, they are the longest-lived rodents known. And remarkably, they appear able to maintain good health for most of their lives. At an age equivalent to a human age of 92 years, naked mole-rats show unchanged levels of activity and metabolic rate, as well as sustained muscle mass, fat mass, bone density, cardiac health, and neuron number.

So not only they are exceptionally long-lived, they are also very active and healthy even in the old age.

Somehow they delay the onset of aging and compress the period of decline into a small fraction of their overall lifespan.

They also have no cancer.

Naked mole rates are exceptions to several theories of aging. For example, the free radical theory states that aging happens, because of the extensive cellular damage from reactive oxygen species. However, naked mole rats show very high levels of oxidative damage from these free radicals and still their cells are perfectly functioning for years and years. Another hypothesis claims that aging is due to shortening of telomeres – DNA molecules caps, that shorten every time a cells undergoes division. Yet the naked mole rat has relatively short telomeres. Also the telomerase, protein that lengthens telomeres, is not really active in naked mole rats’ cells. So telomere maintenance is unlikely to explain the outstanding longevity in these animals.

So what are the reasons for these almost “magical” properties of the naked mole rat? Park and Buffenstein note:

1. Naked mole-rat tissues are better able to recognize abnormal cells, neutralize their tumorigenic properties, and repair their DNA. Should that fail, the cells are ushered into programmed cell death pathways.  This means that errors in the DNA are constantly and effectively repaired or removed, before they give rise to cancer.

2. Many gene families in the mole-rat genome are involved in DNA repair and detoxification processes, and the expression of these genes remains unchanged as the animals age. So, stress resistance genes work perfectly well into the old age.

3. Proteasomes are more abundant and more efficient in degrading the damaged proteins within the cells. Same thing with autophagy – it occurs at a twofold greater rate in naked mole-rat cells than those of the mouse. These two enchanted mechanisms of cellular cleaning resist damage from toxins, heavy metals and DNA-damaging agents. In simple words: better housekeeping means longer life.

This supermodel for research is being studied only in a couple of labs in the world. This is such a shame. I wish more researchers included naked mole rats in their experiments. I wish there were more money for research in naked mole rats, because they may hold the keys to our understanding of the mechanisms responsible for life extension.

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People Who Justify Aging are Profoundly Wrong – Aging is Abhorrent

I have read this recent opinion in the New York Times “Age and Its Discontents” by author Louis Begley and it resonated so much with my personal feelings about the topic. The author vividly describes the last years of his mother’s life, who had been a widow for the previous 40 years before her death. Begley lets us feel the pain in her joints and in her heart. He obviously sees aging as nothing but misery and loneliness. But I think he misses the point – he believes his mother’s solitude is the reason of her woes, but it actually is aging, her declined health, pain and suffering – these are the real reasons of her tragedy. If she had been young she would have had no diseases, but only good looks and the opportunity to start over, but alas! she rot alive. Louis Begley caught the very overwhelming in its inevitability, horrifying feeling that it’s all over, no need to buy new costumes. They will not be worn for a long time and they’re not worth spending time and money.

Mr. Begley was widely criticized – and by whom? Who do you think justified aging?  Executive director and chief scientific officer of the Alzheimer’s Drug Discovery Foundation wrote:

Mr. Begley’s bitter portrayal of aging is neither universal nor inevitable.

This is unbelievable. So wrong. In reality it’s exactly the opposite – aging is universally debilitating and inevitable. While this type of words are coming out of the mouths of people who are the advocates for aging research, nothing good will happen. There will be no money for research to live longer in a younger body. And the reason is the faulty idea that aging can be healthy, productive, or enjoyable. It can’t by definition. Aging is the worst thing and it’s happening to everyone of us every second of our lives, sucking up our strength, youth and beauty. I want to fight this widely spread idea of how old age is full of pleasure, when your grandchildren sit on your lap. Sure, that’s nice, but it’s not even remotely enough. For example, it would be much better to have the possibility to go to a night club after your grandchildren’s visit and be able dance all night long. But this can never happen while we have leaders of Alzheimer’s Drug Discovery Foundations saying that aging is ok. Opinion leaders have to understand how harmful justifying aging is – this position is killing us.

And I want to live. I want all the people on Earth to live. In order to achieve this everybody who is involved in the field of aging has to be more courageous. They have to speak up for themselves and for their work. They have to say that they want to fight aging, that they want life extension. Cancer researchers say that cancer is their greatest enemy, that cancer has to be illuminated and viola – the amount of money that went to cancer research from the National Cancer Institute in 2010 was almost 5.1 billion dollars – that’s like 5 times more than on aging. And cancer is just an individual case of an aging-related pathology. We have to learn from oncologists, cancer researchers and advocates. We are fighting aging and we have to speak about it freely and explicitly. Make no mistake – our goal is to defeat aging completely.

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