A Novel View of Inflammaging

Inflammaging is a term coined to describe one way in which the immune system runs awry with age. Like a malfunctioning thermostat, the level of inflammatory response is consistantly too high, leading to damage to aged tissue:

Inflammation is necessary to cope with damaging agents and is crucial for survival, particularly to cope with acute inflammation during our reproductive years. But chronic exposure to a variety of antigens, especially to some viruses such as cytomegalovirus, for a period much longer than that predicted by evolution, induces a chronic low-grade inflammatory status that contributes to age-associated morbidity and mortality. This condition carries the proposed name "inflammaging".

I noticed a paper today which contains an interesting take on how inflammation leads to damage. It's not just the inflammatory response, per this theory, but also the anti-inflammatory systems evolved to shut off an inflammatory response after it has served its purpose. If inflammation is constantly jammed on, then so is the anti-inflammatory system - based on the hormone cortisol - that is trying to shut it down. So you have at once all the downsides of both a constantly active immune system, and an immune system that is constantly damped down: damage from constant activity yet poor immune response when you do need it to fight off disease:

"Inflamm-aging" denotes the up-regulation of certain pro-inflammatory cytokines at older ages, and associated chronic diseases. It is well known that blood levels of cortisol also increase with age, an increase commonly considered to be due to activation of the Hypothalamus-Pituitary-Adrenal (HPA) axis by many non-specific stressors.

On the contrary, herein I describe how the activation of Hypothalamus-Pituitary-Adrenal (HPA), far from being unspecific, constitutes: a) the main specific response and counterbalance to "Inflammaging" ('anti-inflammaging'), b) an explanation for the well known paradox of immune-senescence: i.e. the coexistence of inflammation and immunodeficiency, as well as c) a complex mechanism of remodelling elicited by inflammaging, explaining the long and winding pathophysiological road that goes from robustness to frailty.

Indeed, the phenomenon of anti-inflammaging, mainly exerted by cortisol, with the passage of time becomes the cause of a marked decline of immunological functions, and its coexistence with the increased levels of pro-inflammatory cytokines of inflammaging, ultimately have negative impacts on metabolism, bone density, strength, exercise tolerance, the vascular system, cognitive function, and mood. Thus inflammaging and anti-inflammaging together determine many of the progressive pathophysiological changes that characterize the "aged-phenotype", and the struggle to maintain robustness finally results in frailty.

The author points to cortisol, and if you look at the Wikipedia entry you will see touches upon a wide range of vital systems in the body. If inflammation is always on, then excess cortisol is constantly trying to turn it off, causing harm along the way.

Fortunately solutions to prevent the immune system from getting into this state in the first place are within sight. If the medical research community makes a sane shift from a philosophy of futile attempts to patch up the end results of aging to preventing and reversing specific degenerations earlier in life, then I imagine we'll see a range of ways to restore a damaged immune system in the clinic by 2030. Have a look back in the Fight Aging! archives for some pointers:

Comments

One thing that confuses me related to this is fish oils. They get advertised as reducing inflammation... yet increasing metabolism... but if metabolism causes inflammation... how's that work?

Posted by: Tycio at March 2nd, 2009 8:23 PM

Inflammation, more specifically chronic systemic inflammation (metaflammation, pseudo inflammation, inflammaging), is not caused by metabolism per say. It has many causes with the prime areas being nutrition and lifestyle. At a cellular level a prime component is the effects from advanced glycation end products (AGEs), its receptor (RAGEs), and their ligands.

Posted by: Dr. Joseph B. Gentzel, PT, DPT at October 2nd, 2012 1:28 AM

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