It is well known that the immune response decreases during aging, leading to a higher susceptibility to infections, cancers and autoimmune disorders. Most widely studied have been alterations in the adaptive immune response. Recently, the role of the innate immune response as a first-line defence against bacterial invasion and as a modulator of the adaptive immune response has become more widely recognized. One of the most important cell components of the innate response is neutrophils and it is therefore important to elucidate their function during aging. With aging there is an alteration of the receptor-driven functions of human neutrophils, such as superoxide anion production, chemotaxis and apoptosis. One of the alterations underlying these functional changes is a decrease in signalling elicited by specific receptors. Alterations were also found in the neutrophil membrane lipid rafts. These alterations in neutrophil functions and signal transduction that occur during aging might contribute to the significant increase in infections in old age.

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Alzheimer’s disease (AD) is the most frequent type of dementia. The pathological hallmarks of the disease are extracellular senile plaques composed of beta-amyloid peptide (Aβ) and intracellular neurofibrillary tangles composed of pTau. These findings led to the “beta-amyloid hypothesis” that proposes that Aβ is the major cause of AD. Clinical trials targeting Aβ in the brain have mostly failed, whether they attempted to decrease Aβ production by BACE inhibitors or by antibodies. These failures suggest a need to find new hypotheses to explain AD pathogenesis and generate new targets for intervention to prevent and treat the disease. Many years ago, the “infection hypothesis” was proposed, but received little attention. However, the recent discovery that Aβ is an antimicrobial peptide (AMP) acting against bacteria, fungi, and viruses gives increased credence to an infection hypothesis in the etiology of AD. We and others have shown that microbial infection increases the synthesis of this AMP. Here, we propose that the production of Aβ as an AMP will be beneficial on first microbial challenge but will become progressively detrimental as the infection becomes chronic and reactivates from time to time. Furthermore, we propose that host measures to remove excess Aβ decrease over time due to microglial senescence and microbial biofilm formation. We propose that this biofilm aggregates with Aβ to form the plaques in the brain of AD patients. In this review, we will develop this connection between Infection – Aβ – AD and discuss future possible treatments based on this paradigm.

Research Methods and Procedures:In this cross-sectional study, 22 healthy obese postmenopausal women (mean age, 66 Ϯ 5 years; mean BMI, 27 Ϯ 3 kg/m 2 ) were divided into two groups matched for age (Ϯ2 years) and fat mass (FM) (Ϯ2%). Sarcopenia was defined as a muscle mass index of Ͻ14.30 kg fat-free mass (FFM)/m 2 (which corresponds to 1 standard deviation below the values of a young reference population), and obesity was defined as an FM of Ͼ35% (which corresponds to the World Health Organization guidelines). FM, FFM (measured by DXA), daily energy expenditure (accelerometry), dietary intake (3-day dietary record), and blood biochemical analyses (lipid profile, insulin, glucose, and C-reactive protein) were obtained. Visceral fat mass (VFM) was calculated by the equation of Bertin, which estimates VFM from DXA measurements. Results: Obese women had more FFM (p ϭ 0.006), abdominal FM (p ϭ 0.047), and VFM (p ϭ 0.041) and a worse lipid profile [p ϭ 0.040 for triglycerides; p ϭ 0.004 for high-density lipoprotein (HDL); p ϭ 0.026 for total cholesterol/HDL] than sarcopenic-obese postmenopausal women. Obese women also ingested significantly more animal (p ϭ 0.001) and less vegetal proteins (p ϭ 0.013), although both groups had a similar total protein intake (p ϭ 0.967). Discussion: Sarcopenia seems to be associated with lower risk factors predisposing to CVD in obese postmenopausal women. With the increase in the number of aging people, the health implications of being sarcopenic-obese merit more attention.

The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detrimental consequences. This dichotomy is influenced by both the genetics and the environment. Depending on which way prevails in an individual, the outcome may be healthy longevity or pathological aging burdened with aging-related diseases. The concept of inflammaging has also revealed the complex, systemic nature of aging. Thus, this conceptualization opens the way to consider age-related processes in their complexity, meaning that not only the process but also all counter-processes should be considered. It has also opened the way to add new concepts to the original one, leading to better understanding of the nature of inflammaging and of aging itself. Finally, it showed the way towards potential multimodal interventions involving a holistic approach to optimize the aging process towards a healthy longevity.