The Strategies for Engineered Negligible Senescence (SENS) is a view of aging as accumulated damage. Drawing from the extensive scientific literature on aging, the originators of SENS created an outline of the forms of cell and tissue damage that are fundamental causes of aging, in that they occur as a natural side-effect of the normal operation of our cellular biochemistry. So we might consider the loss of vital cells due to declining stem cell function, mutations to nuclear DNA and mitochondrial DNA, cross-linking of vital molecules in the extracellular matrix, accumulated metabolic waste in ..read more

Lipid metabolism is changed and disrupted with advancing age, as is the case for all complex mechanisms in the body. There are a great many different lipids present in the body; even the list of classes of lipid is a long one. Finding specific changes that relate to aging can be interesting, but the challenge lie in better understanding how those changes come about, and whether they causes significant harm to tissues. Many age-related changes in molecular biochemistry are far downstream of the important causes of aging and do not cause much further disruption in and of themselves. In recent y ..read more

The consensus of the research community on senescent cells in old tissues is that (a) their presence causes harm, and (b) treatments based on the selective removal of such cells will be beneficial, reversing many aspects of aging and age-related disease. These cells secrete a pro-inflammatory mix of signal molecules that is disruptive to tissue structure and function when maintained over time. Cells become senescent constantly throughout life, only to be destroyed by programmed cell death or by the immune system. With advancing age, newly created senescent cells are cleared ever more slowly, h ..read more

The balance of microbial populations making up the gut microbiome is different from individual to individual, and changes with age in detrimental ways. Pro-inflammatory microbes, as well as those that create otherwise harmful metabolites, expand in number at the expense of microbial populations that produce beneficial metabolites. Evidence strongly suggests that both variations between individuals and age-related changes in the gut microbiome can contribute to age-related disease and mortality. Here, for example, a study in rabbits shows that specific differences in the gut microbiome correlat ..read more

As some of you may know, I co-founded Repair Biotechnologies with Bill Cherman. The company is presently on the development of a gene therapy approach now demonstrated to rapidly reverse atherosclerosis in mice, the condition in which fatty plaques grow to narrow blood vessels and weaken blood vessel walls. One of the possible approaches to treating aging as a medical condition is to take the list of causes of human mortality, start at the top, and work down. Atherosclerosis is the single largest cause of death in our species, through the rupture of unstable atherosclerotic plaque leading to h ..read more

Species that exhibit negligible senescence tend to be long-lived, but more interestingly appear to exhibit few to none of the functional declines of degenerative aging until very late in life, quite unlike the situation for most mammals, and particularly for humans. One can argue that the most useful species that exhibit negligible senescence are those with near relative species that age more normally. The closer the relative, the more likely it is that comparing the biochemistry of the two will lead to new knowledge regarding aging. So naked mole rats versus other, less long-lived mole rats ..read more

A number of large epidemiological studies provide evidence for long-term exposure to greater levels of air pollution to accelerate the onset and progression of age-related disease. A few of these manage to control for the tendency for wealthier people to avoid living in areas with higher particulate air pollution, and the correlation with worse health remains. Mechanistically, it is thought that particulates provoke greater chronic inflammation via their interaction with lung and other tissues, and this in turn contributes to the cell and tissue dysfunction that leads to age-related disease ..read more

Many compounds are now known to have some positive influence on mitochondrial function. The biochemistry is complex and incompletely understood. Even in the well-studied cases, there are hypotheses regarding the mechanism of action, but little certainty. In general, improvement of the quality control mechanism of mitophagy appears to be a necessary factor in the improvement of mitochondrial function in old tissues, but that appears to happen as the result of many different types of intervention. Here, researchers note that a class of bacterial peptides originating from the gut microbiome appea ..read more

Past evidence has suggested that the lowered body temperature characteristic of calorie restriction is important to the slowed aging that results in short-lived mammals. One might compare that to the strong evidence for upregulated autophagy to be the driving factor in slowed aging produced by the practice of calorie restriction. Researchers here conduct a similar study, inducing a reduction in metabolic rate, dietary intake, and body temperature in mice via activation of a specific brain region. As in past research, the resulting slowed aging was shown to be driven by that lowered body temper ..read more

Cells become senescent in response to damage, a toxic environment, the signaling of nearby senescent cells, or, most commonly, because they reach the Hayflick limit on replication. Senescent cells cease replication and begin to secrete pro-inflammatory signals, attracting the attention of the immune system. With advancing age he aged immune system becomes less able to clear senescent cells in a timely manner, leading to a growing, permanent presence of senescent cells in tissues. Some of these senescent cells are themselves immune cells. Given the importance of the immune system to tissue main ..read more