Today I thought I'd point out a few recent papers and publicity materials on muscle aging. A large chunk of the research into stem cell aging and changes in cell metabolism with aging focus on muscle tissue. In part this is a feedback loop: the better understood models and types of cell are found in or associated with muscle tissue. Therefore more researchers use this as a starting point, and therefore the knowledge grows faster than is the case for other tissue types. It doesn't hurt that muscle tissue is easily sampled and examined in people and animals, unlike the cell populations of internal organs. That reduces the cost across the board for many types of study, and researchers are very conscious of cost - there is no such thing as a laboratory with enough funding for optimal progress. Measured by deeds rather than words, our society places very little value on medical research, or indeed research at all for that matter. The investment that goes into building the scientific understanding necessary to produce better medicine is minuscule in the grand scheme of things. Thus a core skill for any scientist to be able to do more with less, because less is absolutely the state of things.
Muscle mass and strength diminishes with aging. It is called sarcopenia in those who suffer this loss to a significantly greater degree, and there has been an ongoing effort for the past decade to formally define this condition within the US regulatory system. That this process is still underway, and with no end in sight, is a sign of just how much that system holds back progress. It thus remains illegal to try to commercialize therapies for sarcopenia, and that is felt all the way back down the chain of research and development in the form of reduced availability of funding. There are many mechanisms involved in muscle degeneration in aging, ranging from the characteristic reduction in stem cell activity in old tissues to the effects of chronic inflammation, passing through mitochondrial dysfunction and numerous other metabolic changes that impair aspects of muscle growth or operation. As is always the case, definitively linking the observed changes into lines of cause and consequence is a challenge. Clinics will be repairing aging with SENS rejuvenation therapies long before the research community can produce a comprehensive, detailed model of aging that traces every step from fundamental damage through to final end stage of disease.
You may find the research linked here interesting, but remember that it's a thin slice of a large and diverse selection of scientific initiatives. These are small snapshots in an evolving album relating to muscle aging, and that in turn is but a small part of the larger field.
Researchers used human embryonic stem cells to create a kind of cell, called a cardiac mesoderm cell, which has the ability to turn into cardiomyocytes, fibroblasts, smooth muscle, and endothelial cells. All these types of cells play an important role in helping repair a damaged heart. As those embryonic cells were in the process of changing into cardiac mesoderms, the team was able to identify two key markers on the cell surface. The markers, called CD13 and ROR2, pinpointed the cells that were likely to be the most efficient at changing into the kind of cells needed to repair damaged heart tissue. The researchers then transplanted those cells into an animal model and found that not only did many of the cells survive but they also produced the cells needed to regenerate heart muscle and vessels.
"In a major heart attack, a person loses an estimated 1 billion heart cells, which results in permanent scar tissue in the heart muscle. Our findings seek to unlock some of the mysteries of heart regeneration in order to move the possibility of cardiovascular cell therapies forward. We have now found a way to identify the right type of stem cells that create heart cells that successfully engraft when transplanted and generate muscle tissue in the heart, which means we're one step closer to developing cell-based therapies for people living with heart disease."
Skeletal muscle has a remarkable capacity to regenerate by virtue of its resident stem cells (satellite cells). This capacity declines with aging, although whether this is due to extrinsic changes in the environment and/or to cell-intrinsic mechanisms associated to aging has been a matter of intense debate. Furthermore, while some groups support that satellite cell aging is reversible by a youthful environment, others support cell-autonomous irreversible changes, even in the presence of youthful factors. Indeed, whereas the parabiosis paradigm has unveiled the environment as responsible for the satellite cell functional decline, satellite cell transplantation studies support cell-intrinsic deficits with aging.
In this review, we try to shed light on the potential causes underlying these discrepancies. We propose that the experimental paradigm used to interrogate intrinsic and extrinsic regulation of stem cell function may be a part of the problem. The assays deployed are not equivalent and may overburden specific cellular regulatory processes and thus probe different aspects of satellite cell properties. Finally, distinct subsets of satellite cells may be under different modes of molecular control and mobilized preferentially in one paradigm than in the other. A better understanding of how satellite cells molecularly adapt during aging and their context-dependent deployment during injury and transplantation will lead to the development of efficacious compensating strategies that maintain stem cell fitness and tissue homeostasis throughout life.
Mitochondrial membrane potential is the major regulator of mitochondrial functions, including coupling efficiency and production of reactive oxygen species (ROS). Both functions are crucial for cell bioenergetics. We previously presented evidences for a specific modulation of adenine nucleotide translocase (ANT) appearing during aging that results in a decrease in membrane potential - and therefore ROS production - but surprisingly increases coupling efficiency under conditions of low ATP turnover. Careful study of the bioenergetic parameters of isolated mitochondria from skeletal muscles of aged and young rats revealed a remodeling at the level of the phosphorylation system, in the absence of alteration of the inner mitochondrial membrane (uncoupling) or respiratory chain complexes regulation.
For equivalent ATP turnover (cellular ATP demand), coupling efficiency is even higher in aged muscle mitochondria, due to the down-regulation of inner membrane proton leak caused by the decrease in membrane potential. In the framework of the radical theory of aging, these modifications in ANT function may be the result of oxidative damage caused by intra mitochondrial ROS and may appear like a virtuous circle where ROS induce a mechanism that reduces their production, without causing uncoupling, and even leading in improved efficiency. Because of the importance of ROS as therapeutic targets, this new mechanism deserves further studies.
Loss of muscle mass and force occurs in many diseases such as disuse/inactivity, diabetes, cancer, renal, and cardiac failure and in aging - sarcopenia. In these catabolic conditions the mitochondrial content, morphology and function are greatly affected. The changes of mitochondrial network influence the production of reactive oxygen species (ROS) that play an important role in muscle function. Moreover, dysfunctional mitochondria trigger catabolic signaling pathways which feed-forward to the nucleus to promote the activation of muscle atrophy. Exercise, on the other hand, improves mitochondrial function by activating mitochondrial biogenesis and mitophagy, possibly playing an important part in the beneficial effects of physical activity in several diseases. Optimized mitochondrial function is strictly maintained by the coordinated activation of different mitochondrial quality control pathways. In this review we outline the current knowledge linking mitochondria-dependent signaling pathways to muscle homeostasis in aging and disease and the resulting implications for the development of novel therapeutic approaches to prevent muscle loss.