An Overview of Inflammaging and Mitochondrial Damage
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With advancing age - and accumulating damage - the immune system moves into a state wherein it is constantly roused and on alert, exacting a toll on the integrity of tissue and cells through its signaling and activity, but also ineffective at actually tackling pathogens, senescent cells, precancerous cells, and other things that should be destroyed. So you have constant chronic inflammation and all its downsides with none of the compensatory immune activity boost that comes with short-term inflammation in the young. Researchers have given the name "inflammaging" to this progressive and increasingly harmful disarray of the immune system, and you'll find a few introductions to inflammaging as a concept back in the Fight Aging! archives.

Below is an open access paper that gives an overview of inflammaging and how it relates to some of the forms of cellular damage that cause aging. In this paper, the researchers paint a picture of inflammaging derived from root causes that involve mitochondrial damage and progressive failure of autophagy to clear out that damage, two line items that have been examined a fair number of times here in the past - under the Strategies for Engineered Negligible Senescence (SENS) viewpoint these two are amongst the fundamental, root causes of aging.

Inflammaging: disturbed interplay between autophagy and inflammasomes

In 2000, Franceschi et al. coined the term "inflammaging" in order to refer to a low-grade pro-inflammatory status appearing during the aging process. They emphasized the role of macrophages as well as cellular stress and genetic factors in the generation of the inflammaging condition. In addition, they hypothesized that this inflammatory environment could predispose the organism to the development of several age-related diseases. During recent years, this scenario has been confirmed by a plethora of experimental evidence. ... Interestingly, the aging process is simultaneously accompanied by both the features accelerating inflammaging and the counteracting, so-called anti-inflammaging characteristics. It seems that the balance between these opposite forces controls the outcome of the aging process, either leading to frailty and degenerative diseases or a healthy old age and longevity.

...

The aging process is associated with a decline in autophagic capacity which impairs cellular housekeeping, leading to protein aggregation and accumulation of dysfunctional mitochondria which provoke reactive oxygen species (ROS) production and oxidative stress.

Recent studies have clearly indicated that the ROS production induced by damaged mitochondria can stimulate intracellular danger-sensing multiprotein platforms called inflammasomes. [As a result of inflammasome activity, signaling molecules called] cytokines provoke inflammatory responses and accelerate the aging process by inhibiting autophagy.

There has been some good progress in recent years in pulling things together in the big picture - and the more that we see the mechanisms of SENS featured, the better to my eyes. That ways lies increased support for rejuvenation biotechnology that will actually work to reverse aging, rather than the present mainstream course of aiming to slow down aging just a little sometime in next few decades.

Comments

'they hypothesized that this inflammatory environment could predispose the organism to the development of several age-related diseases.'
Then remove chronic low level inflammation from the environment to slow the aging process. How best to accomplish that feat? So far as I've been able to find out there in the www, and I'm no scientist, the anatabine alkaloid found in nightshade plants is the most effective anti-inflammatory substance w/o negative side effects. Is that the answer?

Posted by: texrunner at March 16, 2012 9:56 AM

@textrunner: Regular moderate exercise plus calorie restriction is more effective than any presently available medical technology or ingested substance for long term reduction in inflammation levels for the vast majority of people.

Posted by: Reason at March 16, 2012 10:23 AM
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