In order to maintain muscle strength, muscle cells must get rid of the intracellular garbage that accumulates over time. In the case of muscle cells, this garbage includes old organelles such as mitochondria and endoplasmic reticuli, clumps of damaged proteins, and free radicals, all of which can become cytotoxic over time. By recycling mitochondria, muscle fibers boost energy production and preserve muscle function.
If muscle fibers fail to clear these potentially dangerous entities, they will become smaller and weaker. It is now well known that the levels of circulating hormones and growth factors drastically decrease with age and that this has an effect on muscle aging. Indeed, hormone replacement therapy can efficiently reverse muscle aging, in part by activating pathways involved in protein synthesis. Moreover, the muscle itself is a secretory endocrine organ. Proteins produced by the muscle when it contracts flow into the blood, either on their own or encased in membrane-bound vesicles that protect them from degradation by circulating enzymes.
Bente Pedersen of the Centre of Inflammation and Metabolism and Centre for Physical Activity Research in Denmark was the first to use the term myokine to describe these proteins. Secreted myokines can act locally on muscle cells or other types of cells such as fibroblasts and inflammatory cells to coordinate muscle physiology and repair, or they can have effects in distant organs, such as the brain.
Although several of these myokines have been identified—in culture, human muscle fibers secrete up to different proteins—researchers have only just begun to understand their role in muscle aging. The first myokine to be identified, interleukin-6 IL-6 , participates in muscle maintenance by decreasing levels of inflammatory cytokines in the muscle environment, while increasing insulin-stimulated glucose uptake and fatty-acid oxidation.
Elderly people with high circulating levels of IL-6 are more prone to sarcopenia. Another myokine, insulin-like growth factor 1 IGF-1 , can trigger the swelling of muscle fibers, including after exercise. IGF-1 levels decrease with age, as do levels of the cell-surface receptor that IGF-1 binds to, and mice that overexpress IGF-1 are resistant to age-related sarcopenia. When injected into old mice, apelin boosted the formation of new mitochondria, stimulated protein synthesis, autophagy, and other key metabolic pathways, and enhanced the regenerative capacity of aging muscle by increasing the number and function of satellite cells.
As with IGF-1, levels of circulating apelin declined during aging in humans, suggesting that restoring apelin levels to those measured in young adults may ameliorate sarcopenia. Although the causes of muscle loss are numerous and complex, there is now copious evidence to suggest that exercise may prevent or reverse many of these age-related changes, whereas inactivity will accelerate muscle aging. More surprisingly, the immune system had not aged much either. For example, the number of satellite cells can be increased by exercise, and active elderly people have more of these cells than more-sedentary individuals do.
This is the reason why exercise prior to hip and knee surgery can speed up recovery in the elderly. A lack of exercise decreases the efficiency and number of mitochondria in skeletal muscle, while exercise promotes mitochondrial health. Exercise can even spur muscle cells to maintain more-youthful levels of gene transcripts and proteins. For example, Sreekumaran Nair from the Mayo Clinic in Rochester, Minnesota, and colleagues found that high-intensity aerobic interval training reversed many age-related differences in muscle composition, including restoring mitochondrial protein levels.
Additionally, exercise improved muscle function: the older adults were 59 percent weaker than the younger adults before training, and only 38 percent weaker afterward. Exercise may prevent or reverse many of these age-related changes, whereas inactivity will accelerate muscle aging. Exercise also appears to influence autophagy.
In December , Sandri and his colleagues were the first to report, in mice, that autophagy activity could be boosted by voluntary physical activity, in this case, running on a treadmill. Finally, exercise can also apparently restore levels of myokines that decline with age. For example, when elderly subjects followed a regular program of physical activity, there was a direct correlation between the improvement in their physical performance and the increase in the level of circulating apelin. By these mechanisms and others we have yet to discover, exercise can improve overall strength in the elderly, and specifically, the metabolic vigor of skeletal muscle.
Being the most abundant tissue in the average human body, accounting for 30 percent to 40 percent of its total mass, muscle is not only critical for locomotion and breathing, but also for glucose, lipid, and amino-acid homeostasis. The age-associated loss of muscle mass and quality thus contributes to the general metabolic dysfunction commonly seen in elderly patients.
In older women, one hour of brisk walking produced elevated insulin sensitivity on the following day. A detailed understanding of the molecular and cellular pathways involved in muscle aging could pave the way for the development of therapeutic interventions to boost protein synthesis and increase muscle mass. For now, regular exercise combined with good nutrition is still the most effective way to fight sarcopenia, and possibly aging overall.
In addition to detailing the underlying causes of muscle aging, future research should seek to define optimal physical exercise and nutritional programs to combat age-related muscle loss and weakness. It may not significantly increase human lifespan, but it will certainly help people reach the end of their lifespan in a healthier condition.
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At the same institution, Vincent Mouly studies muscle regeneration in health and disease, Anne Bigot studies muscle aging, and Capucine Trollet studies age-related muscle disease and gene therapy. Rather, Bruce Carlson was Faulkner's collaborator. In addition, the online version showed an image of smooth muscle. This has been replaced with one of skeletal muscle to more accurately reflect the content of the article. Finally, a misleading sentence about the role of satellite cells in muscle aging has been removed.
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Merkle's method certainly wasn't published first, but he is often credited to have had the idea first. An interesting question, maybe, but who really knows? Because of the nature of the work, GCHQ kept the original memos classified. In , however, the GCHQ changed their posture when they realized that there was nothing to gain by continued silence. Documents show that a GCHQ mathematician named James Ellis started research into the key distribution problem in and that by , James Ellis, Clifford Cocks, and Malcolm Williamson had worked out all of the fundamental details of PKC, yet couldn't talk about their work.
They were, of course, barred from challenging the RSA patent! Hash functions, also called message digests and one-way encryption , are algorithms that, in essence, use no key Figure 1C.
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Instead, a fixed-length hash value is computed based upon the plaintext that makes it impossible for either the contents or length of the plaintext to be recovered. Hash algorithms are typically used to provide a digital fingerprint of a file's contents, often used to ensure that the file has not been altered by an intruder or virus. Hash functions are also commonly employed by many operating systems to encrypt passwords. Hash functions, then, provide a mechanism to ensure the integrity of a file. This is an important distinction.
Suppose that you want to crack someone's password, where the hash of the password is stored on the server.
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Indeed, all you then need is a string that produces the correct hash and you're in! However, you cannot prove that you have discovered the user's password, only a "duplicate key.
Message Digest MD algorithms: A series of byte-oriented algorithms that produce a bit hash value from an arbitrary-length message. MD2 has been relegated to historical status, per RFC MD4 has been relegated to historical status, per RFC MD5 RFC : Also developed by Rivest after potential weaknesses were reported in MD4; this scheme is similar to MD4 but is slower because more manipulation is made to the original data. MD5 has been implemented in a large number of products although several weaknesses in the algorithm were demonstrated by German cryptographer Hans Dobbertin in "Cryptanalysis of MD5 Compress".
In , NIST announced that after reviewing 64 submissions, the winner was Keccak pronounced "catch-ack" , a family of hash algorithms based on sponge functions. The NIST version can support hash output sizes of and bits. Zheng, J. Pieprzyk and J. Seberry, a hash algorithm with many levels of security. HAVAL can create hash values that are , , , , or bits in length.
Whirlpool : Designed by V. Rijmen co-inventor of Rijndael and P. Whirlpool operates on messages less than 2 bits in length and produces a message digest of bits. The design of this hash function is very different than that of MD5 and SHA-1, making it immune to the same attacks as on those hashes. A root hash is used on peer-to-peer file transfer networks, where a file is broken into chunks; each chunk has its own MD4 hash associated with it and the server maintains a file that contains the hash list of all of the chunks.