Progress & Prospects: Gene therapy in aging

Abstract

Studies performed on various experimental model systems indicate that genetic interventions can increase longevity, even if in a highly protected laboratory condition. Generally, such interventions required partial or complete switching off of the gene and inhibiting the activity of its gene products, which normally have other well-defined roles in metabolic processes. Overexpression of some genes, such as stress response and antioxidant genes, in some model systems also extends their longevity. Such genetic interventions may not be easily applicable to humans without knowing their effects on human growth, development, maturation, reproduction and other characteristics. Studies on the association of single nucleotide polymorphisms and multiple polymorphisms (haplotype) in genes with human longevity have identified several genes whose frequencies increase or decrease with age. Whether genetic redesigning can be achieved in the wake of numerous and complex epigenetic factors that effectively determine the life course and the life span of an individual still appears to be a 'mission impossible'.

Suitability of the clonal marbled crayfish for biogerontological research: a review and perspective, with remarks on some further crustaceans

“…Age-related changes of the genome-wide DNA methylation patterns in various tissues could be determined by restriction landmark genomic scanning even without knowing particular genes (Thompson et al 2010). The marbled crayfish could also be used to study the influence of epigenetic interventions on ageing and longevity, for instance by feeding methyl depleted and methyl enriched diets or by inhibition of methyltransferases (Cooney et al 2002;Rattan and Singh 2009;Kuck et al 2010).…”

The NetAge database: a compendium of networks for longevity, age-related diseases and associated processes

“…A recently discovered epigenetic mechanism of RNA interference includes miRNAs as key players, acting predominantly at the post-transcriptional level (Fire et al 1998;Meister and Tuschl 2004). The dysregulations in epigenetic control could have a profound impact on both aging and ARDs (Budovsky et al 2006;Feinberg 2008;Liang et al 2009;Rattan and Singh 2009;Wang 2007). As we have recently shown (Tacutu et al 2010;Wolfson et al 2008), many established miRNAs have the potential to target the genes involved in the control of lifespan, in aging and ARDs.…”

A metabolic and functional overview of brain aging linked to neurological disorders

“…Recently Rattan and Singh (2009) have reviewed and evaluated the scientific basis for developing potential therapies and modes of intervention in the process of aging, with special reference to involving gene therapy, the authors have also discussed the biological understanding of aging, a well understood problem in biology. Age related neurological disorders like Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM) are conditions that affect a large number of people, both conditions are on the increase and finding novel treatments to cure or prevent them are a major aim in research.…”