The nuclear transcription factor NF-kappaB plays a prominent role in one of the advanced theories of aging, Programmed genetic changes. Several new pieces of research highlight the mechanisms by means of which this multi-faceted substance impacts on aging and the importance of the anti-aging firewall substances that inhibit the expression of NF-kappaB. I mention two such studies.
One study has to do with the role of Tumor Necrosis Factor (TNF) activating the expression of NF-kappaB in Muscle Progenitor Cells (MPC). This study is also relevant to the fourteenth theory of aging, Decline in adult stem cell differentiation. TNF acts via a number of pathways in a complicated manner including activation of NF-kappaB to produce a variety of effects including induction of apoptosis (cell suicide). This apoptosis is useful when cancers are concerned but is also potentially destructive of healthy cells. It appears that in MPC cells at least, TNF-alpha activates NF-ÎºappaB more in older animals than in younger ones. This leads to apoptotic signaling and death of MPC. The problem is thought to be a decline in age of effective cellular mechanisms for keeping NF-kappaB inactive. Practically speaking, this appears to support the importance of the thirty-nine anti-aging firewall substances that inhibit the expression of NF-kappaB.
A second study has to do with the role of the sirtuin SIRT6 in regulating the expression of NF-kappaB. Another member of the sirtuin family, SIRT1, has been extensively studied and even sometimes referred to as a key “longevity gene.” But SIRT6 also seems to play an important role in keeping NF-kappaB expression in its proper place. SIRT6 works with NFkappa-B to control the activity of genes connected with metabolism, inflammation, immunity and aging. When SIRT6 is in short supply, NFkappa-B becomes hyperactive and turns up activity of aging-linked genes. “We propose that SIRT6 attenuates NF-kappaB signaling via H3K9 deacetylation at chromatin, and hyperactive NF-kappaB signaling may contribute to premature and normal aging.” Again, taking the firewall substances that control expression of NFkappa-B may be an effective anti-aging measure.