Ultimately, we would like to provide a general metabolic model for long-life - one that quantitatively explains longevity in terms of the expression of genes that encode metabolic enzymes, the activity of those enzymes, and the metabolic concentrations and fluxes that result from them.
This popularity originates from a high safety record and the longevity of transgene expression in neurons.
While the presence and activity of p53 was demonstrated to enhance longevity by upregulating the expression of potent antioxidants, the sestrins, life span is enhanced by the loss of GRF1, which is accompanied by a downregulation of IGF1.
The data we have obtained so far from dual AAV vectors up to 9 months after retinal gene delivery, the last time point of our analysis, suggest that longevity of transgene expression may be similar between single normal size and dual AAV vectors.
As such, improved stability and longevity of gene expression can be expected.
Epigenetic alterations of the expression of longevity genes by changing the level/pattern of histone acetylation may be an important factor in determining the longevity of animals [ 41, 42].
This observation suggested that X-linked hypomethylated DMGs may contribute to gender gap of human longevity, which is consistent with the hypothesis that gender-specific regulation of longevity may be related to the expression of sex hormone patterns [ 38].
The longevity of Aβ42-expressing flies, for both expression levels, was significantly increased by co-expression of the BRICHOS domain, resulting in a median lifespan of 62 and 58 days for Aβ42×1 + BRICHOS and Aβ42×2 + BRICHOS flies, respectively (P<0.0001) (Fig. 1B,C; see supplementary material Table S2).
This result strongly suggests that elevated hepatic Foxo1 expression contributes to the longevity of the Brandt's bat.
55, 56 Future clinical experiments should address these risks, as well as continue to optimize vectors for improved potency and longevity of expression.
22 AAV vectors have been shown to be notably less potent at stimulating innate immune pathways, 23 which appears to be a significant factor in their enhanced longevity of expression in animal models.
