Category Archives: Longevity Medicine

Inevitably, researchers who focus on slowing aging through metabolic manipulation will uncover ingested compounds that alter metabolism in beneficial ways, and thus very modestly raise life expectancy. Here is an example in mice: "Recent evidence points to a strong relationship between increased mitochondrial biogenesis and increased survival ... Branched-chain amino acids (BCAAs) have been shown to extend chronological life span in yeast. However, the role of these amino acids in mitochondrial biogenesis and longevity in mammals is unknown. Here, we show that a BCAA-enriched mixture (BCAAem) increased the average life span of mice. BCAAem supplementation increased mitochondrial biogenesis and sirtuin 1 expression in primary cardiac and skeletal myocytes and in cardiac and skeletal muscle, but not in adipose tissue and liver of middle-aged mice, and this was accompanied by enhanced physical endurance. Moreover, the reactive oxygen species (ROS) defense system genes were upregulated, and ROS production was reduced by BCAAem supplementation. All of the BCAAem-mediated effects were strongly attenuated in [mice engineered to lack] endothelial nitric oxide synthase." Nitric oxide is important to stem cell and blood vessel function; it is interesting that this effect depends upon that component of metabolism.

View the Article Under Discussion: http://dx.doi.org/10.1016/j.cmet.2010.08.016

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

A brief summary of recent research into risk factors for disease and human longevity: "A set of currently known alleles increasing the risk for coronary artery disease, cancer, and type 2 diabetes as identified by genome-wide association studies was tested for compatibility with human longevity. Here, we show that nonagenarian siblings from long-lived families and singletons older than 85 [years] of age from the general population carry the same number of disease risk alleles as young controls. Longevity in this study population is not compromised by the cumulative effect of this set of risk alleles for common disease." The way in which you choose to lead your life is a more important determinant - for example, being sedentary and fat raises your risk of suffering the common diseases of aging far more than most known genetic variants. It is true that there are many gene variants associated with exceptional human longevity, but it still seems to be the case that environment and choice trumps small variations in your biology.

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20921414

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Your cells are constantly creating and destroying the protein components of their machinery. All of the known metabolic alterations that enhance longevity affect these processes in some way: "Cellular homeostasis, which is needed for the cells to survive, requires a well-controlled balance in protein turnover. Both protein synthesis and degradation are influenced by distinct genetic pathways that control aging in divergent eukaryotic species. ... In addition to providing building blocks for generation of new proteins and fuelling the cell with energy under starvation, the protein degradation processes eliminate damaged, nonfunctional proteins, the accumulation of which serves as the primary contributory factor to aging. Interestingly, a complex, intimate regulatory relationship exists between mechanisms promoting protein synthesis and those mediating protein degradation: under certain circumstances the former downregulate the latter. Thus, conditions that favor protein synthesis can enhance the rate at which damaged proteins accumulate. This may explain why genetic interventions and environmental factors (e.g., dietary restriction) that reduce protein synthesis, at least to tolerable levels, extend lifespan and increase resistance to cellular stress in various experimental model organisms of aging."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20886758

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Looking back at historical data on life span in human lineages, researchers find the result you might expect from centenarian studies - the most long-lived families tend to have more long-lived offspring, while for everyone else lifestyle choices and accident are more important determinants: "Although genetic factors are known to influence the human aging process, the proportion of life span and longevity variation explained by them is still controversial. We evaluated the genetic contribution to life span using historical data from three Alpine communities in South Tyrol, Italy. We estimated the heritability of life span and survival to old age (longevity), and we assessed the hypothesis of a common genetic background between life span and reproduction. The heritability of life span was [low], whereas the heritability of longevity [increased] as the longevity threshold increased. Heritability estimates were little influenced by shared environment, most likely due to the homogeneity of lifestyle and environmental factors in our study population. Life span showed both positive association and genetic correlation with reproductive history factors. Our study demonstrates a general low inheritance of human life span, but which increases substantially when considering long-living individuals, and a common genetic background of life span and reproduction, in agreement with evolutionary theories of aging."

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20884848

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Thoughts on the impact of better technology on free radical theory: "The role of oxidative stress in aging proposed by the free radical theory has been the focus of investigations for more than fifty years. The results of a large number of these investigations provide support for this theory. However, numerous recent findings point to the existence of unexpected complexity in the relationships between oxidative stress and aging. This complexity is highlighted by the discovery [that] a key element of oxidative stress defenses in the model organism budding yeast, shortens lifespan in concert with enhanced resistance to oxidative stress. In addition to the implications of this finding for understanding aging, identification of this mutation by massively parallel sequencing of whole genomes emphasizes the enormous utility of next-generation sequencing technologies as investigative tools that will likely revolutionize genetics. ... In some cases, the apparent disconnect between experimental results and predictions of the free radical theory regarding connections between oxidative stress and lifespan is related to hormesis effects that elevate oxidative and other stress defenses in response to low levels of oxidative stress. ... The more transparently clear lesson here is that not all forms of oxidative stress are equivalent in their effects on aging. This isn't surprising in the context of the multitude of pathways that respond to different forms of oxidative stress and the numerous mechanisms by which oxidants can modify different macromolecular targets. Whatever the explanation, [research findings] emphasize the enormous complexity of relationships between oxidative stress and aging."

View the Article Under Discussion: http://www.impactaging.com/papers/v2/n8/full/100188.html

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/