Category: Blog

Efficient, safe methods of gene therapy will be essential enabling technologies for the repair or obviation of several of the cellular and molecular lesions driving age-related disease and dysfunction. A recent paper from the Scripps Institute demonstrates a major step in this direction with the successful use of helper-dependent adenoviral vectors to rescue cells defective in lamin A, without detectable mutational side-effects.

At the third SENS conference, Dr. Samit Adhya of the Indian Institute of Chemical Biology presented a proof-of-principle for the use of an RNA import complex adapted from the parasite Leishmania to import arbitrary antisense RNA strands into mammalian mitochondria, reducing levels of a target protein by RNA interference. In a new study, Adhya’s group reports the successful use of the same technique to deliver mRNA sequences corresponding to proteins of the electron transfer chain, rescuing mitochondrial function in cells with mutations or deletions in those genes.

Much of the distraction in the literature of biogerontology, and an even higher ratio of studies cited and promoted in the popular media and the dietary supplement industry, derives from methodologically-poor lifespan studies in mice (or occasionally rats). In these studies, an increase in mean or maximal lifespan is reported, relative to short-lived controls, and claimed to be informative about the universal, degenerative aging process and the prospects for extending healthy life in humans living in the developed world.

The free radical theory of aging suggests that reactive oxygen species (ROS) and similar chemicals are responsible for a large part, or perhaps all, of the molecular and cellular damage that accumulates in aging bodies. However, more detailed analysis has revealed that some free radicals have essential signalling functions within the cell. These functions are likely to explain some of the failure of antioxidant therapy to extend lifespans in model organisms.

Beginning in the 1960s, a loose alliance led by social gerontologists but quickly coming to include biogerontologists, geriatricians, and patient advocacy groups successfully campaigned for a new understanding: that while some level of minor cognitive decline was indeed a “normal” and inevitable part of aging, the newly-rediscovered clinicopathological entity, “Alzheimer’s disease,” was exactly that: a disease, against which the full force of public and private biomedical research should be mobilized in the pursuit of a cure.

The degenerative aging of the immune system is responsible for an enormous burden of disease and disability, from the pain of recurrent Herpes zoster and postherpetic neuralgia, to elevated rates of chronic urinary tract infections, to complications in wounds, pressure sores, ulcers, and surgical incisions. Most prominently, it underlies the meteoric rise in mortality from respiratory infections with age: influenza, pneumonia, and septicemia rise from being negligible causes of death in healthy middle-aged adults in the USA, to emerge amongst the top 10 causes of death in adults over the age of 55, with mortality rates climbing with each successive year of aging.

Zinc finger nucleases (ZFNs) are engineered DNA-binding proteins with remarkable, highly programmable sequence-specificity. However, their widespread use has been slowed by licensing issues and the technical difficulty of synthesising new variants. A new platform, CoDA (context-dependent assembly), promises to make these exceptionally useful tools available to a far greater number of researchers.

Induced pluripotent stem cells (iPSCs) are among the most exciting recent developments in biomedicine, overcoming immunological and ethical issues associated with the use of embryonic stem cells (ESCs). However, reasonable doubt remains regarding whether iPSCs do in fact have the full biological and therapeutic potential of ESCs. Work at the Harvard Stem Cell Institute recently produced the first “all-iPSC” live mice, a milestone on the road to establishing full equivalence between the two methods.