Inflammaging as a Major Characteristic of Old People: Can It Be Prevented or Cured?

Department of Experimental Pathology and Interdepartmental Centre L. Galvani at the University of Bologna, Bologna, Italy.
Nutrition Reviews (Impact Factor: 6.08). 12/2008; 65(12 Pt 2):S173-6. DOI: 10.1301/nr.2007.dec.S173-S176
Source: PubMed


Widespread aging at the population level is a recent phenomenon that emerged in affluent societies. 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". Centenarians are unique in that, despite high levels of pro-inflammatory markers, they also exhibit anti-inflammatory markers that may delay disease onset. The key to successful aging and longevity is to decrease chronic inflammation without compromising an acute response when exposed to pathogens.

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    • "The number of astrocytes, at least in human brains, for which the relevant counts were performed (Pelvig et al., 2008; Fabricius et al., 2013), does not change with age, remaining unaffected even in centenarians (Fabricius et al., 2013). Although the concept of the age-dependent increase in astroglial reactivity is quite widespread (Unger, 1998; Lynch et al., 2010) and is used to corroborate the ideas of the so called ''inflammaging'' (Franceschi, 2007), which regards brain senescence as a chronic neuroinflammation; the experimental data on this matter are, however, controversial. In aged animals a decrease (e.g. "
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    ABSTRACT: Astrocytes are fundamental for homoeostasis, defence and regeneration of the central nervous system. Loss of astroglial function and astroglial reactivity contribute to the ageing of the brain and to neurodegenerative diseases. Changes in astroglia in ageing and neurodegeneration are highly heterogeneous and region-specific. In animal models of Alzheimer's disease (AD) astrocytes undergo degeneration and atrophy at the early stages of pathological progression, which possibly may alter homeostatic reserve of the brain and contribute to early cognitive deficits. At the later stages of AD reactive astrocytes are associated with neurite plaques, the future commonly found in animal models and in human diseased tissue. In animal models of the AD reactive astrogliosis develops in some (e.g. in the hippocampus) but not in all regions of the brain. For instance, in entorhinal and prefrontal cortex astrocytes to not mount gliotic response to emerging β-amyloid deposits. This deficits in reactivity coincides with higher vulnerability of these regions to AD-type pathology. Astroglial morphology and function can be regulated through environmental stimulation and/or medication suggesting that astrocytes can be regarded as a target for therapies aimed at prevention and cure of neurodegenerative disorders. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 01/2015; DOI:10.1016/j.neuroscience.2015.01.007 · 3.36 Impact Factor
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    • "These systemic toxicities were closely representative of those previously noted clinically with FDA­approved immu­ nostimulatory IT therapeutics such as high­dose IL­2 and IFN­ (Lee and Margolin, 2011). Aging is associated with a gradual decline in immunolog­ ical function but is also accompanied by the coincidence of a systemic, chronic, and low­grade proinflammatory response termed inflammaging that leads to increased systemic cyto­ kine levels, namely IL­1, IL­6, and TNF (Franceschi, 2007). "
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    ABSTRACT: Aging is a contributing factor in cancer occurrence. We recently demonstrated that systemic immunotherapy (IT) administration in aged, but not young, mice resulted in induction of rapid and lethal cytokine storm. We found that aging was accompanied by increases in visceral fat similar to that seen in young obese (ob/ob or diet-induced obese [DIO]) mice. Yet, the effects of aging and obesity on inflammatory responses to immunotherapeutics are not well defined. We determine the effects of adiposity on systemic IT tolerance in aged compared with young obese mice. Both young ob/ob- and DIO-generated proinflammatory cytokine levels and organ pathologies are comparable to those in aged ad libitum mice after IT, culminating in lethality. Young obese mice exhibited greater ratios of M1/M2 macrophages within the peritoneal and visceral adipose tissues and higher percentages of TNF(+) macrophages in response to αCD40/IL-2 as compared with young lean mice. Macrophage depletion or TNF blockade in conjunction with αCD40/IL-2 prevented cytokine storms in young obese mice and protected from lethality. Calorie-restricted aged mice contain less visceral fat and displayed reduced cytokine levels, protection from organ pathology, and protection from lethality upon αCD40/IL-2 administration. Our data demonstrate that adiposity is a critical factor in the age-associated pathological responses to systemic anti-cancer IT.
    Journal of Experimental Medicine 11/2014; 211(12). DOI:10.1084/jem.20140116 · 12.52 Impact Factor
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    • "Elevated concentrations have been measured in the bronchoalveolar lumen in patients with asthma compared to normal healthy individuals and concentrations further increase after birch pollen provocation (Lundstrom et al., 2012). These elevated concentrations of pro-inflammatory oxylipins in the older age group reported here, therefore, may provide mechanistic information to explain the higher levels of inflammation in older versus younger individuals (Franceschi, 2007). Our findings are also consistent with the increased prevalence of inflammatory related conditions such as arthritis, diabetes, hypertension, and obesity with increased age (Statistics Canada, 2013). "
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    ABSTRACT: Oxylipins, including the eicosanoids, are highly bioactive molecules endogenously produced from polyunsaturated fatty acids. Oxylipins play a key role in chronic disease progression. It is possible, but unknown, if oxylipin concentrations change with the consumption of functional foods or differ with subject age. Therefore, in a parallel comparator trial, 20 healthy individuals were recruited into a younger (19-28 years) or older (45-64 years) age group (n=10/group). Participants ingested one muffin/day containing 30g of milled flaxseed (6g alpha-linolenic acid) for 4weeks. Plasma oxylipins were isolated through solid phase extraction, analyzed with HPLC-MS/MS targeted lipidomics, and quantified with the stable isotope dilution method. At baseline, the older group exhibited 13 oxylipins≥2-fold the concentration of the younger group. Specifically, pro-inflammatory oxylipins 5-hydroxyeicosatetraenoic acid, 9,10,13-trihydroxyoctadecenoic acid, and 9,12,13-trihydroxyoctadecenoic acid were significantly greater in the older (1.1±0.23 nM, 5.6±0.84 nM, and 4.5±0.58 nM, respectively) versus the younger group (0.34±0.12 nM, 3.5±0.33 nM, and 3.0±0.24 nM, respectively) (p<0.05). After 4weeks of flaxseed consumption the number of oxylipins that were≥2-fold higher in the older versus the younger group was reduced to 3. 5-hydroxyeicosatetraenoic acid, 9,10,13-trihydroxyoctadecenoic acid, and 9,12,13-trihydroxyoctadecenoic acid decreased in the older group to concentrations equivalent to the younger group after flaxseed consumption. These data suggest a potential role for oxylipins in the aging process and how nutritional interventions like flaxseed can beneficially disrupt these biological changes associated with inflammation and aging.
    Experimental gerontology 04/2014; 59. DOI:10.1016/j.exger.2014.04.005 · 3.49 Impact Factor
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