Reading Level: In-Depth

Two quarter-century long studies on the effects of Calorie restriction in nonhuman primates have come to opposing results. What do these results mean for the human translatability of CR, and the future of therapies to prevent and cure the diseases and disabilities of aging?

“Reprogramming” of adult differentiated cells into pluripotent stem cells is an exciting method in biology that holds enormous promise for rejuvenation biotechnology. Now, for the first time, Dr. Su-Chun Zhang and coworkers at the University of Wisconsin-Madison have successfully generated neurons from reprogrammed nonhuman primate cells, transplanted them back into the same animal’s brain, and seen them successfully and cleanly integrate into the local tissue.

The preliminary results of a clinical trial for a disease of “premature aging” – Hutchinson-Gilford Progeria Syndrome (HGPS) – are hopeful and inspiring. However, they cannot directly inform the development of rejuvenation biotechnologies; although the symptoms of HGPS are similar to those observed in aging, there is no evidence to suggest that the underlying mechanism is pathologically significant in those not afflicted with the disease.

Aging laboratory rodents are the foundation of our ability to study the degenerative aging process, and develop the rejuvenation biotechnologies that will arrest and reverse it. They’re also expensive, logistically intensive, and in short supply. A new UK initiative has been establish to greatly expand what we can learn from the aging animals in our collective care, and to get a fuller picture of aging and its deceleration and reversal than has hitherto been possible.

Recent studies show the potential – and the limits – of inducing telomerase expression in aging mice. We place these results in context and explore their implications for new treatments targeting age-related degeneration in humans, particularly examining how telomerase activity relates to the development of cancer.

SENS Foundation-funded research shows that expression of a modified microbial enzyme protects human cells against 7-ketocholesterol toxicity, advancing research toward remediation of the foam cell and rejuvenation of the atherosclerotic artery.

UCLA Researchers have exploited a recently-discovered mammalian system for the mitochondrial import of nuclear-encoded RNA to import, express, and demonstrate functional protein translation from engineered mRNA and tRNA constructs. They used this system, with modifications for mitochondrial targeting and orthotopic translation, to rescue respiration in human mitochondriopathy cells. While further characterization and extension is clearly needed, this approach appears offer great promise for the correction of age-related mitochondrial DNA mutations.

The promising results of immunotherapy for the treatment and prevention of Alzheimer’s disease has sparked an interest in utilizing the same approach for other forms of aging damage, including the clearance of pathological tau species from within neurons. A group led by Dr. Lars Ittner of the University of Sydney has recently published promising results from studies using a vaccine targeted at the neurofibrillary tangles (NFTs) that are characteristic of established tau accumulation.

APBs – protein complexes associated with telomeric DNA in ALT (Alternative Lengthening of Telomeres) cancer cells – are the leading candidates for the sub-cellular site at which the ALT mechanism occurs. Recent work involving the generation of artificial APBs has shed light on their composition and function, providing hints as to how ALT might be disabled.

Parkinson’s disease is characterised by the loss of dopaminergic neurons from the substantia nigra, and cell therapy is being actively pursued as a means to replace the losses. Most trials to date have used fetal tissue, an approach that although transiently effective is unscalable and prone to immune rejection. Human dopaminergic neurons differentiated from stem cells have historically had poor therapeutic efficiency, but a new study using an improved differentiation protocol has shown much more positive results.