Hypothesis:
chronic
antigenic and inflammatory burden plays a pivotal role for human frailty and survival
Hypothesis:
chronic
antigenic and inflammatory burden plays a pivotal role for human frailty and survival
old people have to cope with a lifelong antigenic burden encompassing several decades of evolutionary unpredicted antigenic exposure
Remodelling / Stress response Inflammatory response Optimal remodeling (hormesis)
Low proinflammatory status
High efficiency of stress response Inadequate remodeling
High proinflammatory status
Low efficiency of stress response Effects of stress AGE
INFLAMM-AGING
IL-6
30 60 90 C - males have higher serum IL-6 in respect to age-matched
C+ males and C+/C- females C- Males C- Females C+ Females C+ Males Genotype-sex interaction Age Serum IL-6
IL-10
Inflamm-aging
IL-10
IL-10 is a major immunoregulatory cytokine which inhibits activation and effector function of T cells, monocytes and macrophages, and its principal routine function appears to limit and ultimately terminate inflammatory responses
MALES Il - 10 "Functional Genotype" Il - 10 high production Il - 10 Low production Controls (89) % 27 73 N 24 65 Centenarians (65) % 44,6 55,4 N 29 36 Pearson Chi - square test: 5.184; df:1; p:0.026
IL-6 and IGF1
INS/IGF1 R HUMANS Insulin/IGF-1 p85/p110 a-b IRS1 HNF3/Forkhead LONGEVITY DEVELOPMENT GLUCOSE METABOLISM NEMATODE FLY MOUSE INR b INR Chico IRS1-2 Dp110/p60 p85/p110a-b ? Forkhead transcription factor Insulin/IGF-1 Ligand DAF-2 ? AGE 1 DAF-16 Ligand GH GHR (-/-) INSULIN/IGF-1 SIGNALING PATHWAY: HUMAN HOMOLOGIES WITH NEMATODE, FLIES AND MICE
Am. J. Physiol. Endocrinol. Metab. 284: E481-E487, 2003
Table 2. Correlations between IL-6, IL-6 receptor and IGF-1 and anthropometric and physical performance parameters (n=526) IL-6* p IL-6 receptor p IGF-1 p Age 0.36 <.001 0.16 <.001 -0.25 <.001 BMI 0.14 <.003 -0.04 NS -0.23 <.001 Handgrip -0.17 <.001 -0.03 NS 0.14 <.05 Total power -0.14 <.005 -0.05 NS 0.15 <.001 * Back log trasformed
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