Tag Archives: negligible senescence

Hacking Aging

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What would you say if I told you that aging happens not because of accumulation of stresses, but rather because of the intrinsic properties of the gene network of the organism? I’m guessing you’d be like: o_0.

So, here’s the deal. My biohacker friends led by Peter Fedichev and Sergey Filonov in collaboration with my old friend and the longevity record holder Robert Shmookler Reis published a very cool paper. They proposed a way to quantitatively describe the two types of aging – negligible senescence and normal aging. We all know that some animals just don’t care about time passing by. Their mortality doesn’t increase with age. Such negligibly senescent species include the notorious naked mole rat and a bunch of other critters like certain turtles and clams to name a few. So the paper explains what it is exactly that makes these animals age so slowly – it’s the stability of their gene networks.

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Fours Stages of Curing Aging

Masha pink hair

Curing aging has 4 stages: mild aging deceleration, dramatic aging deceleration, achieving negligible senescence and rejuvenation. Today we can definitively claim that the task of mild aging deceleration is theoretically solved.

We know the drugs and interventions that slow down aging in mammals. The only thing that we don’t know is dosages, regimes and drug combinations. Defining all of that is the goal of pre-clinical and clinical studies. They can be started immediately. It is also a good idea to do clinical studies of various diets aimed at improving human longevity.

Dramatic aging deceleration will be achieved using gene therapy. Breakthrough studies of lifespan extension in old model animals happened in this area quite recently. We know the genes and delivery methods, now we need a set of powerful experiments aimed at radical life extension. The subject of the intervention will not only be the human genome, but the genomes of the human microbiota.

Rearrangement of how the genome works, as well as genetically modified stem cell therapy and therapeutic cloning can provide negligible senescence.

However, rejuvenation of the organism is likely to be competing with the idea and the very possibility of changing the body as the personality substrate to something else. It is likely that our goal will be not the youth, but creating a more advanced organism capable of solving the task of its own indestructability.

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Genome of Long-Lived Brandt’s Bat Sheds Some Light to Its Exceptional Longevity

Brandt's bat

 

Congratulations to my colleague, Dr. Alexey Moskalev, who, with collaboration with Dr. Vadim Gladyshev, published this awesome paper on genetic basis of exceptional longevity of the Brandt’s bat. This is an amazing animal – it lives up to more than 40 years of age, but weighs only 4-8 grams. A tiny “centenarian” creature. It lives in caves, sleeps during the day, echolocates and hibernates during winter. Every trait has its genetic background. The authors tried to decipher the background of the bat’s longevity.

The most important thing that they found was that Brandt’s bat has altered growth hormone and insulin growth factor 1 signaling (GH/IGF1). This signaling is reduced, there is a kind of dysfunction, that contributes to the animal’s longevity along with the adaptations like hibernation and low reproduction rate. There are other interesting findings. For example, olfactory function is also reduced in these amazing animals. It’s interesting, because olfactory system plays a role in regulating longevity. For example, if you put drosophilas on a restricted diet, they start to live longer, but if you let them smell food, then life extension effect goes away.

I think that this work is crucial, because if we are able to identify the genes that are responsible to exceptional longevity in species like naked mole rats, whales and rougheye rockfish, we’d be able to find the way to alter the activity of those longevity genes in our bodies, for example, pharmacologically. Eventually this will lead to creating life extension therapies that would make us live longer, healthier and happier lives.

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The main question in Biogerontology

mechanisms of aging, white-footed mouse, lab mouse, mice, aging, fight aging, aging research, biogerontology, funding, stress resistance, oxidative stress, George Sacher, long-lived animals, negligible senescence, naked mole rat
There’s this quite simple idea: to take two species similar in size and basic biology, but having a substantial difference in longevity, and figure out what’s the reason for this difference. What are the distinctions in the mechnisms of aging and stress resistance? It’s desirable to carry out this work in various species. However, not a lot of people are excited about this simple idea. Even the genome of the famous naked mole rat has not been sequenced yet, although many people believe it’s got “negligible” senescence.

For now all that we have is negligible funding of evolutionary-comparative biology of aging. Moreover, previously obtained results are put into cold storage.

In 1962 George Sacher began laboratory breeding of wild-caught house mice (Mus musculus) and white-footed mice (Peromyscus leucopus) trapped near the Argonne Laboratory site in northeast Illinois. The maximal lifespan of the white-footed mouse turned out to be more than 8 years, contrary to 3,5 years in either wild-caught or laboratory house mice. Sacher’s laboratory publiched about a dozen papers comparing house and white-footed mice, as did Ron Hart’s laboratory in the National Center for Toxicological Research.

There’s no need to say that George Sacher was given grants mostly for works in the area of radiological protection, and aging research was mostly funded by means of the lab’s own resources.

Since the beginning of the 1980s research was just middling, but still something was found out.

Below are some data from the works of Ungvary et al. and Labinskyy et al. Basicly this table shows the major known differences between the species. The autors claim that these data correspond with the oxidative stress theory of aging.

mechanisms of aging, white-footed mouse, lab mouse, mice, aging, fight aging, aging research, biogerontology, funding, stress resistance, oxidative stress, George Sacher, long-lived animals, negligible senescence, naked mole rat
Still a lot of questions can be addressed to the white-footed mouse. For example, what is the destinction in the stress resistance mechanisms? What’s with its regeneration capacity? What if we compare it with the naked mole rat? And here comes the main question in Biogerontology. Why is the research into the fundamental mechanisms of aging so scarcely funded?

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Main questions of Biology of Aging

main questions of biology of aging, problem, question, negligible senescence, aging, fighting aging, mechanisms of aging, neurogenesis, inflammation, regeneration, stress response, anti-aging, oncogenesisHere
are the main questions in the Biology of Aging. I suggest that the specialists
should extend the list of questions. And maybe, formulate the problems in more
detail. Everybody is welcome to express their opinion and suggest some
answers.

1. What are the mechanisms responsible for the differences in life expectancy within one species and between species?
2. Why do experimental impacts, like caloric restriction, delay the
onset of a number of age-related physiological and pathological changes
and increase the average and maximal life span in animals?
3. What is the relationship between aging and pathology?
4. At what stage of evolution did aging emerge?
5. How did the mechanisms of aging and anti-aging evolve?
6. What are the mechanisms of relationship between aging of an organism and aging on cellular level?
7. What is the reason for the existence of species with negligible aging?
8. How are reproduction and lifespan interrelated?
9. What is aging?
10. Why is there a decline in regenerative potential of an organism over time?
11. What is the role of epigenetic regulation during aging?
12. What is the role of inflammation in aging processes?
13. What is the role of genomic instability in aging processes?
14. What interventions in aging processes could extend the maximal lifespan of model animals and humans?
15. What is the effect of aging on the cells’ and organisms’ energy supplies and vica versa?
16. What is the role of the neuroendocrinal system in the regulation of aging processes?
17. What is the distinction of centenarians as compared to the whole population?
18. How relevant to humans are the results of life extension research on model animals?
19. What is essential for creating the unified synthetic theory of aging?
20. How did animals with negligible senescense evolve?
21. What are the factors influencing differences in the rate of aging among individuals?
22. What are the mechanisms of aging in cancer cells?
23. What is the relationship between aging and oncogenesis?
24. When does aging begin in humans?
25. When do manifestations of aging begin?
26. What are the molecular biological mechanisms of regeneration during sleep?
27. What is necessary for the creation of an exhaustive list of biomarkers of aging?
28. Can neurogenesis be stimulated?
29. What are the mechanisms of how higher nervous system activity influences the mechanisms of aging?
30. What are the factors defining the rate and efficiency of stress responses?

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