Category Archives: Mechanisms of aging

Genetics of Aging and Longevity Conference – Venue Chosen

One of the best conferences in the world, Genetics of Aging and Longevity conference, will take place on April 6-10 in Sochi, the city of 2014 Olympic Games. A couple of words about the event – the best geneticists of aging will gather to share their latest research on

  • Longevity genes in human and animals
  • Epigenetic mechanisms of aging
  • Inflammation and hyperfunction, intertwined mechanisms of aging?
  • Environment, genes and aging
  • Biomarkers of biological age
  • Pharmacological interventions in aging
  • Strategies for regenerative medicine applied to humans
  • Systems biologyof aging and longevity
  • Comparative biology of lifespan
  • Oxidative damage and aging

And now we know the place where the magic will happen – Radisson Blu Resort & Congress Center. Here are the pictures of the place.

Don’t forget to register for Genetics of Aging and Longevity here

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Vote Kennedy in the Presidential Election

kennedy-brian-1

If your life depends on someone other than yourself, that would be Brian Kennedy. Dr. Kennedy is the President of the Buck Institute for Research on Aging, a world’s leading research institute that brings together outstanding scientists who work together on solving the mystery of aging and revealing the ways of increasing our health span. Basically, it’s up to the successes of the large team led by Brian Kennedy whether you will live a long and enjoyable life, or not.

An excellent example of my  words is the most recent amazing work done by Dr. Pankaj Kapahi and his research group, who was able to extend nematode’s lifespan 5-fold. The trick was to switch off two genes in one worm simultaneously – the TOR  and the insulin-like growth factor-1 receptor (named daf-2) genes. It has been known that turning off TOR in a worm gives it a 30% longer lifespan, and turning off daf-2 doubles the lifespan. One could think that 100% + 30% = 130%, but Dr. Kapahi’s worms decided they know Math better and lived 5 times longer, proving that sometimes  100% + 30% = 500%. What happened is the synergy between blocking the two aging mechanisms – the TOR and insulin/IGF-1 signaling. I have always said that there are so many things  we know that extend lifespan – let’s try the combinations of those things. Indeed, this proved to be a fruitful strategy. I am looking forward to seeing more and more papers combining different interventions in aging mechanisms and getting synergistic results.

pankaj kapahiPankaj Kapahi's paper

Regardless of the country where you live, it always makes sense to vote for someone who may increase the chances for extending your lifespan. Of course, Dr. Brian Kennedy is not participating in the presidential elections, however it would be excellent if the politicians fought for our lives. I think it’s up to us to demand that the politicians include increasing funding for aging research as part of their programs. We have to show it matters. A lot.

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There Can Be No Healthy Aging

craig-venter3

This is Craig Venter. His institute has received 1.25 million dollars from the Ruggles Family Foundation to study the biomarkers of healthy aging.

The study, conducted by a team of scientists and clinicians from JCVI and WCHN, will focus on two groups of elderly individuals aged 65 to 85 years by correlating genetics with a variety of human genomic, gut microbiome and other “omics” profiles and integrating these data with the individuals’ health record. One group will consist of healthy individuals, and the other will have individuals with a variety of diagnosed health conditions.

This study makes no sense to me, because they want to look at the differences in health between sick people and even sicker people and call the results of the study markers of healthy aging. They propose to measure the right things, but what the study planners are missing here is the fact that aging itself is a disease. Aging can’t be healthy, because the underlying biological mechanisms that are causing age-related pathologies are active also in those aged individuals, who don’t have those diseases. To give you an example – manifestation of type 2 diabetes means that the cells lost their sensitivity to insulin, however really a lot of older people, who don’t have type 2 diabetes, have impaired insulin sensitivity. These people are considered to be just old, but not sick. That’s exactly what’s wrong with perception of aging. Everyone who reached a certain age is considered to be simply old, but not ill. However this person is 100% not healthy in a biological sense, because a lot of detrimental processes have already started their poisonous actions and altered the youthful state of the organism.

In order to find the biomarkers of aging the study design should be different. The control for an individual should be the very same individual. Let me explain. We are very different in the biological sense from each other. So, to draw conclusions about a person’s aging processes, based on a given set of parameters, we have to measure those parameters several times in the beginning of the experiment to identify the baseline for the person. Then by measuring those parameters in the long run we will be able to see the changes in levels and make conclusions regarding the underlying mechanisms of aging. Also that would be the way to judge the efficacy of interventions like caloric restriction and melatonin, or rapamycin, or other drugs. Of course, the exact study design description would be more complicated, I am just pointing out the main things here. But again, the idea is not to distinguish sick people from sick people with diagnosed diseases, the idea is to identify how the sickness, i.e. aging, can be characterized.

Here’s what important – we need to change the perception of aging, so there would be no confusing terms like “healthy aging”, which is an oxymoron. It’s like “dignified poverty”, or “merciful tyrant”. Aging is not and can not be healthy. Aging is itself a disease. It is also the cause of many other maladies like Alzheimer’s and stroke, and many others. We have to stop using the term healthy aging, because it is already making us conduct poorly designed research experiments.

 

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Benjamin Button Jellyfish

immortal jellyfish

I enjoy reading the New York Times so much. Especially when they write about various aspects of aging. This article got my attention, because is even better, it’s about immortality and fighting aging. You have probably heard about the immortal  jellyfish, Turritopsis dohrnii, that instead of dying goes back in time and renews itself to become young again. It’s fascinating. It could give us the clues to make a human being immortal, however I quote:

 You might expect that, having learned of the existence of immortal life, man would dedicate colossal resources to learning how the immortal jellyfish performs its trick. You might expect that biotech multinationals would vie to copyright its genome; that a vast coalition of research scientists would seek to determine the mechanisms by which its cells aged in reverse; that pharmaceutical firms would try to appropriate its lessons for the purposes of human medicine; that governments would broker international accords to govern the future use of rejuvenating technology. But none of this happened.

And this is not the most surprising thing! Do you know how many researchers in the world culture the immortal jellyfish in a lab? Just one. I found this really shocking. There’s only one guy, a Japanese professor Dr. Shin Kubota, who has been keeping a population of  Turritopsis dohrnii in a lab, carefully looking after them and studying them. I believe he is one of the most amazing researchers in the world, because he studies the jelly fish to solve the problem of aging and become immortal. I quote him:

The immortal medusa is the most miraculous species in the entire animal kingdom, I believe it will be easy to solve the mystery of immortality and apply ultimate life to human beings.

That’s the spirit! I believe Dr. Kubota needs all the help in the world to figure out what it is exactly that makes the immortal jelly fish be able to reverse its age backwards. It’s such a shame that he has got no money and no help at all to conduct this kind of research. I understood from the article that other than funding Dr. Kubota needs a molecular biologist and a geneticist to collaborate with to decipher those rejuvenation mechanisms. Anyone interested? Any volunteers? Do I need to say that this is probably the most important research in the history of mankind?

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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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Aging of Stem Cells

Continuing the series of charts describing the mechanisms of aging. Here you can download the pdf the chart about aging of stem cells. Take a look at how telomere shortening, oxidative stress and impaired stem cell niche regulation influences our stem cells: reduces the number of dormant stem cells, reduces their engrafting capacities and leads to aberrant, meaning improper, differentiation.

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Telomeres and Aging Chart

I love charts, because it’s a great way to explain complex biological processes. This chart shows what happens when our telomeres shorten. And the beauty of this series of charts created by Dr. Alexei Moskalev is that we added the definitions of biological phenomena to make the illustrations easier to understand. You are most welcome to download the pdf of the telomeres and aging chart here.

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