The second volume of the new open access journal Pathobiology of Aging and Age-related Disease is available online. I thought I'd point out one of the papers, which argues that the biology of long-lived mouse species should be considered evidence for the importance of chronic inflammation in determining life span.
Mutant animals characterized by extended longevity provide valuable tools to study the mechanisms of aging. Growth hormone and insulin-like growth factor-1 (IGF-1) constitute one of the well-established pathways involved in the regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH deficiency as well as growth hormone receptor / growth hormone binding protein knockout (GHRKO) mice characterized by GH resistance live significantly longer than genetically normal animals.
During normal aging of rodents and humans there is increased insulin resistance, disruption of metabolic activities and decline of the function of the immune system. All of these age related processes promote inflammatory activity, causing long term tissue damage and systemic chronic inflammation. However, studies of long living mutants and calorie restricted animals show decreased pro-inflammatory activity with increased levels of anti-inflammatory adipokines such as adiponectin. At the same time, these animals have improved insulin signaling and carbohydrate homeostasis that relate to alterations in the secretory profile of adipose tissue including increased production and release of anti-inflammatory adipokines.
This suggests that reduced inflammation promoting healthy metabolism may represent one of the major mechanisms of extended longevity in long-lived mutant mice and likely also in the human.
Regular readers will recall that there is a mountain of evidence to link aging and chronic inflammation. If you have higher levels of inflammation, you will have a worse - and usually shorter - time ahead. It causes damage, and that damage adds up; the easiest way in younger life to raise inflammation levels is to become fat, as visceral fat tissue works a number on your metabolism. But everyone's immune system runs off the rails given time, falling into a state wherein it is constantly roused but increasingly ineffective in its designated jobs. Many of the aspects of aging are clearly connected to immune system decline: raised levels of inflammation, increased numbers of senescent cells, increased risk of cancer, and more.
This all argues for some form of safer, more mature version of the immune system reboot therapies that can presently be accomplished, but are not available outside of trials at this time. A large fraction of the immune system's failure with age stems from structural issues: it has evolved to be very, very good at its job in early life, but at the cost of inevitably and predictably failing as it runs out of capacity later on.
Throughout our lives, we have a very diverse population of T cells in our bodies. However, late in life this T cell population becomes less diverse ... [one type of cell] can grow to become more than 80 percent of the total [T-cell] population. The accumulation of this one type of cell takes away valuable space from other cells, resulting in an immune system that is less diverse and thus less capable in effectively locating and eliminating pathogens.
But if the slate could be wiped clean (achieved by chemotherapy at the present time, which is far from ideal) and the immune system repopulated (using stem cells to generate a population of patient-matching immune cells), then this issue vanishes, and people could benefit from a strong immune system for decades longer than is presently the case. That would likely make a significant difference to the course of later life, even in the absence of other advances in medical technology.