Pro-aging is not about letting ourselves go.
S. cerevisiae has also provided some of the initial links between pro-aging pathways and age-dependent genomic instability (McMurray & Gottschling, 2004; Madia et al., 2009).
We instead provide strong evidence that, at physiological levels, acetic acid promotes aging simply by activating pro-aging pathways in yeast, analogously to glucose and ethanol.
The longstanding free radical theory of aging predicts that the pro-aging effects of O2 - are caused by oxidative damage to macromolecules.
On the other hand, artificial activation of p53 results in the abnormal production of a pro-aging phenotype, suggesting that p53 promotes aging only under abnormal or pathological circumstances [ 14].
One possibility is that introducing 'pro-youthful' factors from young blood can reverse age-related impairments in the brain, and a second possibility is that abrogating pro-aging factors from aged blood can counteract such impairments.
Indeed, constitutively activated p53 is considered to be a pro-aging factor, contributing to premature aging phenotypes displayed in mouse models with defects in genome maintenance [27].
All of these findings are consistent with a role for oxidative stress produced in association with growth signaling through highly conserved AKT, TOR and RAS-dependent pathways as an important pro-aging factor in the budding yeast chronological aging model.
Hence, p21 may be a promoter of aging, and as such possibly the effector of the pro-aging characteristics of p53 [ 7].
Increased inflammation has since long been associated with aging [ 58] and we and others have previously provided evidence that this is a major pro-aging phenotype in the mouse [ 59].
Based on these results we hypothesized the tumour suppressive and the pro-aging functions of p53 are managed by two distinct pathways and that p66Shc is a critical component of the aging pathway.
