41 replies to this topic

[Mind]

Researchers boost growth of muscle stem cells to stop age-related muscle deterioration.

[VictorBjoerk]

Researchers boost growth of muscle stem cells to stop age-related muscle deterioration.

Could this mean that old people can potentially get the same maximum heart rate as younger people?

[niner]

Researchers boost growth of muscle stem cells to stop age-related muscle deterioration.

Could this mean that old people can potentially get the same maximum heart rate as younger people?

Probably not, at least until we can also improve the condition of their vasculature. Conboy's work that Mind posted about is pretty exciting. They used techniques (RNAi) that probably rule out a therapy just yet, but it's an example of cellular reprogramming that we can hope will eventually be possible to accomplish with a small molecule treatment or something equally do-able.

[Mind]

Exercise keeps the heart "young"

"We know that the heart deteriorates as people get older, and that's largely because they don't stay as active as they used to," says first author Pablo F. Soto, M.D., instructor in medicine in the Cardiovascular Division. "Past research has suggested that exercise can reverse some effects of aging, and we wanted to see what effect it would have specifically on the heart."

The researchers measured heart metabolism in sedentary older people both at rest and during administration of dobutamine, a drug that makes the heart race as if a person were exercising vigorously. At the start of the study, they found that in response to the increased energy demands produced by dobutamine, the hearts of the study subjects didn't increase their uptake of energy in the form of glucose (blood sugar).

But after endurance exercise training -- which involved walking, running or cycling exercises three to five days a week for about an hour per session -- the participants' hearts doubled their glucose uptake during high-energy demand, just as younger hearts do.

Just another study re-affirming exercise as one of the simplest ways to combat almost every age related malady known.

[aikikai]

Does there exist any current therapy that old people get to increase heart size?

No. Shrinking heart size is not a pathological disease (in medical terms), just part of the aging process. It is not just the heart that is decreasing with age. Even your brain is decreasing with age.

Edited by aikikai, 15 September 2008 - 02:18 PM.

[Mind]

Does there exist any current therapy that old people get to increase heart size?

No. Shrinking heart size is not a pathological disease (in medical terms), just part of the aging process. It is not just the heart that is decreasing with age. Even your brain is decreasing with age.

Not a pathological disease in current medical terms but most certainly pathological to your neighborhood immortalist.

[aikikai]

Does there exist any current therapy that old people get to increase heart size?

No. Shrinking heart size is not a pathological disease (in medical terms), just part of the aging process. It is not just the heart that is decreasing with age. Even your brain is decreasing with age.

Not a pathological disease in current medical terms but most certainly pathological to your neighborhood immortalist.

Certainly yes.
As shrinking heart size is not classified as a pathologial disease, there is no main stream interest to develop therapies to treat the condition. It is like aging, it is not classified as a disease, therefore there is no "direct" development of therapies targeted at aging alone. Problem is also, if something is not classified as a therapy, you are not allowed to develop drugs for a non-pathologial disease.

If we could change the mind of the medical society and governments that aging is a disease, then we would have a much faster development of therapies accredited to aging.

[RENITA]

In a study to be presented Nov. 4 at the American Heart Association's (AHA) annual Scientific Sessions in Orlando, Fla., the Hopkins team analyzed more than a half-dozen measurements of heart structure and pumping function to assess minute changes in the hearts of 5,004 men and women, age 45 to 84, of different ethnic backgrounds and with no existing symptoms of heart disease.This shrinkage will magnify any occlusions that are present, and on systole (when the ventricles of the heart contract to pump blood out), the coronary arteries also contract. You can see the problem here with age. Some occlusion of the coronary arteries, along with shrinkage of the coronary arteries, and with contraction with each heart beat, can lead to a coronary artery occlusive event, or spasm, resulting in angina or a myocardial infarction (heart attack). This occlusion represents what is known as coronary artery disease.
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RENITA


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[Ben K]

Article:

Clues To Reversing Aging Of Human Muscle Discovered

ScienceDaily (Sep. 30, 2009) — A study led by researchers at the University of California, Berkeley, has identified critical biochemical pathways linked to the aging of human muscle. By manipulating these pathways, the researchers were able to turn back the clock on old human muscle, restoring its ability to repair and rebuild itself.

The findings will be reported in the Sept. 30 issue of the journal EMBO Molecular Medicine, a peer-reviewed, scientific publication of the European Molecular Biology Organization.

"Our study shows that the ability of old human muscle to be maintained and repaired by muscle stem cells can be restored to youthful vigor given the right mix of biochemical signals," said Professor Irina Conboy, a faculty member in the graduate bioengineering program that is run jointly by UC Berkeley and UC San Francisco, and head of the research team conducting the study. "This provides promising new targets for forestalling the debilitating muscle atrophy that accompanies aging, and perhaps other tissue degenerative disorders as well."

Previous research in animal models led by Conboy, who is also an investigator at the Berkeley Stem Cell Center and at the California Institute for Quantitative Biosciences (QB3), revealed that the ability of adult stem cells to do their job of repairing and replacing damaged tissue is governed by the molecular signals they get from surrounding muscle tissue, and that those signals change with age in ways that preclude productive tissue repair.

Those studies have also shown that the regenerative function in old stem cells can be revived given the appropriate biochemical signals. What was not clear until this new study was whether similar rules applied for humans. Unlike humans, laboratory animals are bred to have identical genes and are raised in similar environments, noted Conboy, who received a New Faculty Award from the California Institute of Regenerative Medicine (CIRM) that helped fund this research. Moreover, the typical human lifespan lasts seven to eight decades, while lab mice are reaching the end of their lives by age 2.

Working in collaboration with Dr. Michael Kjaer and his research group at the Institute of Sports Medicine and Centre of Healthy Aging at the University of Copenhagen in Denmark, the UC Berkeley researchers compared samples of muscle tissue from nearly 30 healthy men who participated in an exercise physiology study. The young subjects ranged from age 21 to 24 and averaged 22.6 years of age, while the old study participants averaged 71.3 years, with a span of 68 to 74 years of age.

In experiments conducted by Dr. Charlotte Suetta, a post-doctoral researcher in Kjaer's lab, muscle biopsies were taken from the quadriceps of all the subjects at the beginning of the study. The men then had the leg from which the muscle tissue was taken immobilized in a cast for two weeks to simulate muscle atrophy. After the cast was removed, the study participants exercised with weights to regain muscle mass in their newly freed legs. Additional samples of muscle tissue for each subject were taken at three days and again at four weeks after cast removal, and then sent to UC Berkeley for analysis.

Morgan Carlson and Michael Conboy, researchers at UC Berkeley, found that before the legs were immobilized, the adult stem cells responsible for muscle repair and regeneration were only half as numerous in the old muscle as they were in young tissue. That difference increased even more during the exercise phase, with younger tissue having four times more regenerative cells that were actively repairing worn tissue compared with the old muscle, in which muscle stem cells remained inactive. The researchers also observed that old muscle showed signs of inflammatory response and scar formation during immobility and again four weeks after the cast was removed.

"Two weeks of immobilization only mildly affected young muscle, in terms of tissue maintenance and functionality, whereas old muscle began to atrophy and manifest signs of rapid tissue deterioration," said Carlson, the study's first author and a UC Berkeley post-doctoral scholar funded in part by CIRM. "The old muscle also didn't recover as well with exercise. This emphasizes the importance of older populations staying active because the evidence is that for their muscle, long periods of disuse may irrevocably worsen the stem cells' regenerative environment."

At the same time, the researchers warned that in the elderly, too rigorous an exercise program after immobility may also cause replacement of functional muscle by scarring and inflammation. "It's like a Catch-22," said Conboy.

The researchers further examined the response of the human muscle to biochemical signals. They learned from previous studies that adult muscle stem cells have a receptor called Notch, which triggers growth when activated. Those stem cells also have a receptor for the protein TGF-beta that, when excessively activated, sets off a chain reaction that ultimately inhibits a cell's ability to divide.

The researchers said that aging in mice is associated in part with the progressive decline of Notch and increased levels of TGF-beta, ultimately blocking the stem cells' capacity to effectively rebuild the body.

This study revealed that the same pathways are at play in human muscle, but also showed for the first time that mitogen-activated protein (MAP) kinase was an important positive regulator of Notch activity essential for human muscle repair, and that it was rendered inactive in old tissue. MAP kinase (MAPK) is familiar to developmental biologists since it is an important enzyme for organ formation in such diverse species as nematodes, fruit flies and mice.

For old human muscle, MAPK levels are low, so the Notch pathway is not activated and the stem cells no longer perform their muscle regeneration jobs properly, the researchers said.

When levels of MAPK were experimentally inhibited, young human muscle was no longer able to regenerate. The reverse was true when the researchers cultured old human muscle in a solution where activation of MAPK had been forced. In that case, the regenerative ability of the old muscle was significantly enhanced.

"The fact that this MAPK pathway has been conserved throughout evolution, from worms to flies to humans, shows that it is important," said Conboy. "Now we know that it plays a key role in regulation and aging of human tissue regeneration. In practical terms, we now know that to enhance regeneration of old human muscle and restore tissue health, we can either target the MAPK or the Notch pathways. The ultimate goal, of course, is to move this research toward clinical trials."


Abstract:

Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans. Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth factor beta (TGF-)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular understanding, combined with data that human satellite cells remain intrinsically young, introduced novel therapeutic targets. Indeed, activation of MAPK/Notch restored youthful myogenic responses to satellite cells from 70-year-old humans, rendering them similar to cells from 20-year-old humans. These findings strongly suggest that aging of human muscle maintenance and repair can be reversed by youthful calibration of specific molecular pathways.

[Mind]

All is not lost in the fight against muscle shrinkage (including the heart, hopefully) and sarcopenia. Even without new medical/technological breakthroughs, exercise can keep you strong and keep your muscles from deteriorating - even in old age!!

[Destiny's Equation]

I reversed my heart (and other organ) shrinkage by 1. playing around with diet/supplements and 2. exposing myself to 50 degree temperatures. One or the other alone was ineffective, I did not get results until I combined the 2.

I purposely avoided exercise to keep my body temp down.

Before all of my organs were shriveling up rapidly and crumbling to weird prickly dust, now they are re-growing for the most part (they still temporarily backslide into shrinking every once in a while when I make lifestyle mistakes, but what does one expect, we're battling inertia here!)

Disclaimer- I am just judging by signs and symptoms, I was unable to afford imaging etc.

Off to search pubmed to see if this combination has been used before.

[Mind]

Another study regenerating muscle tissue for mice: http://www.scienceda...11129112343.htm

The team used a novel protocol to coax mature human muscle cells into a stem cell-like state and grew those reprogrammed cells on biopolymer microthreads. The threads were placed in a wound created by surgically removing a large section of leg muscle from a mouse. Over time, the threads and cells restored near-normal function to the muscle, as reported in the paper "Restoration of Skeletal Muscle Defects with Adult Human Cells Delivered on Fibrin Microthreads," published in the current issue of the journal

Tissue Engineering Part A

. Surprisingly, the microthreads, which were used simply as a scaffold to support the reprogrammed human cells, actually seemed to accelerate the regeneration process by recruiting progenitor mouse muscle cells, suggesting that they alone could become a therapeutic tool for treating major muscle trauma.

"We are pleased with the progress of this work, and frankly we were surprised by the level of muscle regeneration that was achieved," said Raymond Page, assistant professor of biomedical engineering at WPI, chief scientific officer at CellThera, and corresponding author on the paper.