Giunta S
Clinical Laboratory & Molecular Diagnostics, Geriatric Hospital INRCA-IRCCS-, 60100 Ancona, Italy.
Inflamm Res. 2008 Dec;57(12):558-63. doi: 10.1007/s00011-008-7243-2.
"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 same consequences also result the age-dependent decline of dehydroepiandrosterone (DHEA).
“炎症衰老”指的是某些促炎细胞因子在老年时上调以及相关的慢性疾病。众所周知，皮质醇的血液水平也会随着年龄增长而升高，这种升高通常被认为是由于许多非特异性应激源激活了下丘脑 - 垂体 - 肾上腺（HPA）轴。相反，在本文中，我描述了下丘脑 - 垂体 - 肾上腺（HPA）轴的激活远非非特异性的，它构成了：a）对“炎症衰老”的主要特异性反应和平衡（“抗炎症衰老”），b）对免疫衰老这一众所周知的矛盾现象的解释，即炎症与免疫缺陷的共存，以及c）由炎症衰老引发的一种复杂的重塑机制，解释了从强壮到虚弱的漫长而曲折的病理生理过程。事实上，主要由皮质醇发挥作用的抗炎症衰老现象，随着时间的推移会成为免疫功能显著下降的原因，并且它与炎症衰老中促炎细胞因子水平升高的共存，最终会对代谢、骨密度、力量、运动耐力、血管系统、认知功能和情绪产生负面影响。因此，炎症衰老和抗炎症衰老共同决定了许多表征“老年表型”的渐进性病理生理变化，而维持强壮的努力最终导致虚弱。脱氢表雄酮（DHEA）随年龄增长而下降也会产生同样的后果。
