Why Muscles Weaken With Age and Points to Possible Therapy

http://www.sciencedaily.com/releases/2011/08/110802125549.htm

Sarcopenia, which begins to appear at around age 40 and accelerates after 75, is a major cause of disability in the elderly. Exercise can help counter the effects of age-related muscle loss. sarcopenia occurs when calcium leaks from a group of proteins in muscle cells called the ryanodine receptor channel complex. These leaks then trigger a chain of events that ultimately limits the ability of muscle fibers to contract, leaky ryanodine receptors are involved in the development of heart failure and arrhythmias. In 2009, he showed that leaks in these channels also contribute to Duchenne muscular dystrophy, a genetic disorder characterized by rapidly progressing muscle weakness and early death.

Dr. Marks suspected that ryanodine receptor leakage may also be involved in age-related muscle loss, which the present study shows is the case. "This is a completely new concept -- that the damage that occurs in aging is very similar to what happens in muscular dystrophy," says Dr. Marks, "thus as we age we essentially develop an acquired form of muscular dystrophy."
Both the aging process and the genetic defect responsible for muscular dystrophy cause an increase in the production of oxygen free radicals, highly reactive and harmful molecules. "Our data suggest that this sets up a vicious cycle, in which the free radicals cause ryanodine receptors to leak calcium into the cell. The calcium poisons mitochondria -- organelles that power the cell -- leading to the release of even more free radicals. This, in turn, causes more calcium leakage. With less calcium available for contraction, the muscles get weaker," says first author Daniel C. Andersson, M.D., Ph.D., a postdoctoral fellow in physiology and cellular biophysics at CUMC.
The study also points to a possible therapy for sarcopenia: an experimental drug called S107, developed by Dr. Marks and his colleagues. The drug acts by stabilizing calstabin1, a protein that binds to ryanodine receptors and prevents calcium leakage.
In the study, 24-month-old mice (roughly the equivalent of 70-year-old humans) were given S107 for four weeks. The mice showed significant improvements in both muscle force and exercise capacity, compared with untreated controls. "The mice ran farther and faster during voluntary exercise," says Dr. Andersson. "When we tested their muscles, they were about 50 percent stronger." The drug had no effect on younger mice with normal ryanodine receptors.
A similar drug is now in phase II clinical trials for the treatment of heart failure.
"Most investigators in the field of aging have been saying that the way to improve muscle strength is to build muscle mass, using such therapies as testosterone, growth hormone, and insulin-like growth factor-1," says Dr. Marks. "But an increase in muscle mass is not necessarily accompanied by an increase in muscle function. Our results suggest that you can improve muscle function by fixing leaky calcium channels. And in fact, treating aged mice with S107 enhanced muscle strength without increasing muscle size, at least during the four-week treatment period."

Restoring Happiness in People With Depression

People often underestimate the long-term impact of practicing brief, positive activities, Lyubomirsky said. For example, if a person gets 15 minutes of positive emotions from counting her blessings, she may muster the energy to attend the art class she'd long considered attending, and, while in class, might meet a friend who becomes a companion and confidant for years to come. In this way, even momentary positive feelings can build long-term social, psychological, intellectual, and physical skills and reserves.
The researchers' review of brain imaging studies also led them to theorize that PAIs may act to boost the dampened reward/pleasure circuit mechanisms and reverse apathy -- a key benefit that does not usually arise from treatment with medication alone.
"The positive activities themselves aren't really new," said Layous, the paper's lead author. "After all, humans have been counting their blessings, dreaming optimistically, writing thank you notes, and doing acts of kindness for thousands of years. What's new is the scientific rigor that researchers have applied to measuring benefits and understanding why they work."
A major benefit of positive activities is that they are simple to practice and inexpensive to deliver.
"If we're serious about tackling a problem as large as depression, we should be as concerned about the scalability of our solutions as much as their potency," Chancellor said,
While PAIs appear to be a potentially promising therapy for mild forms of depression," Doraiswamy cautioned, "they have not yet been fully studied in people with moderate to severe forms of depression. We need further studies before they can be applied to help such patients."  http://www.sciencedaily.com/releases/2011/07/110729175803.htm

Some Exercise Is Better Than None: More Is Better to Reduce Heart Disease Risk

http://www.sciencedaily.com/releases/2011/08/110801161414.htm

People who engaged in 150 minutes of moderate-intensity leisure activity had a 14 percent lower risk of coronary heart disease (CHD) compared to those who reported no exercise or physical activity. At higher levels of activity, the relative risk of CHD was progressively lower. Researchers found that even people who got below the United States guidelines for physical activity, which recommends 2 hours and 30 minutes of moderate exercise per week, had a lower risk of CHD than those who had no activity.
"The overall findings of the study corroborate federal guidelines -- even a little bit of exercise is good, but more is better -- 150 minutes of exercise per week is beneficial, 300 minutes per week will give even more benefits," said Jacob Sattelmair, ScD, of the Department of Epidemiology at the Harvard School of Public Health.