Whole-animal senescent cytotoxic T cell removal using antibodies linked to magnetic nanoparticles.

A major type of unwanted cells that accumulate in aging are anergic cytotoxic T cells. These cells often have virus-specific T cell receptors, as well as other surface markers that distinguish them from their youthful counterparts, and they are thought to play a major role in the decline of the immune system with age. Here we consider two surface markers thought to define these cells in mice, CD8 and Killer cell lectin-like receptor G1 (KLRG1), and a means we developed to remove these cells from the blood of aged C57BL/6 mice.

Medical bioremediation: a concept moving toward reality.

Abstract A major driver of aging is catabolic insufficiency, the inability of our bodies to break down certain substances that accumulate slowly throughout the life span. Even though substance buildup is harmless while we are young, by old age the accumulations can reach a toxic threshold and cause disease. This includes some of the most prevalent diseases in old age-atherosclerosis and macular degeneration.

Medical bioremediation of age-related diseases.

Catabolic insufficiency in humans leads to the gradual accumulation of a number of pathogenic compounds associated with age-related diseases, including atherosclerosis, Alzheimer's disease, and macular degeneration. Removal of these compounds is a widely researched therapeutic option, but the use of antibodies and endogenous human enzymes has failed to produce effective treatments, and may pose risks to cellular homeostasis. Another alternative is "medical bioremediation," the use of microbial enzymes to augment missing catabolic functions.

Microbial degradation of 7-ketocholesterol.

7-Ketocholesterol (7KC) is an oxidized derivative of cholesterol suspected to be involved in the pathogenesis of atherosclerosis and possibly Alzheimer's disease. While some oxysterols are important biological mediators, 7KC is generally cytotoxic and interferes with cellular homeostasis. Despite recent interest in preventing the accumulation of 7KC in a variety of matrices to avoid adverse biological effects, its microbial degradation has not been previously addressed in the peer-reviewed literature.

Engineering away lysosomal junk: medical bioremediation.

Atherosclerosis, macular degeneration, and neurodegenerative diseases such as Alzheimer's disease, are associated with the intracellular accumulation of substances that impair cellular function and viability. Reversing this accumulation may be a valuable therapy, but the accumulating substances resist normal cellular catabolism. On the other hand, these substances are naturally degraded in the soil and water by microorganisms.

Cellular therapy using microglial cells.

Recent insights into the function and dysfunction of microglia may inform future therapies to combat neurodegeneration. We hypothesise how different aspects of microglial activity including migration, activation, oxidative response, phagocytosis, proteolysis, and replenishment could be targeted by novel therapeutic approaches. A combined approach is suggested, encompassing opsonization and anti-inflammatory strategies in conjunction with an engineering of microglial precursors.

Making the case for human life extension: personal arguments.

In the close to medium future, the life sciences might permit a vast extension of the human life span. I will argue that this is a very desirable development for the individual person. The question whether death is a harm to the dying is irrelevant here.