Fight Aging!

A few years ago, a Spanish research team created transgenic mice that lived significantly longer than normal by combining increased p53 with increased telomerase. p53 is a cancer suppressor that under usual circumstances reduces the ability of stem cells to replace worn cells in aging tissue - less cell proliferation means a lower chance of cancer over time, but also faster aging as the tissues of the body wear and fail more readily. More telomerase, on the other hand, achieves the opposite end: dynamic, longer lasting cells that also produce way more cancers in the course of their more energetic operations. This, in any case, is the consensus view of how these elements work in the biochemistry of mammals:

The standard reading is that the "Super p53" mice are getting less cancer, but are having their [life spans] restrained by lack of tissue replenishment due to stem cell loss, while the telomerase transgenics are on the opposite horn of the same dilemma. It seems at least possible that if one overlaid the strong cancer resistance conferred by the former, with the increase in stem cell mobilization and proliferative capacity of the latter, you'd wind up with a long-lived, slow-aging mouse.

I should note in passing that it is possible through clever techniques to have enhanced p53 provide both a cancer and longevity benefit in and of itself. But in the case of the Spanish research team, their work is more simply a case of balancing one mixed benefit with the opposite mixed benefit - and coming out ahead of the game. The researchers recently published results for the next stage of their research program: taking the modifications that had been transgenic to date and instead applying them as gene therapies to adult mice. This is a step on the road to building some form of beneficial medical technology for humans:

CNIO scientists successfully test the first gene therapy against aging-associated decline:

Mice treated at the age of one lived longer by 24% on average, and those treated at the age of two, by 13%. The therapy, furthermore, produced an appreciable improvement in the animals' health, delaying the onset of age-related diseases - like osteoporosis and insulin resistance - and achieving improved readings on ageing indicators like neuromuscular coordination.

The gene therapy utilised consisted of treating the animals with a DNA-modified virus, the viral genes having been replaced by those of the telomerase enzyme, with a key role in ageing. Telomerase repairs the extremes of chromosomes, known as telomeres, and in doing so slows the cell's and therefore the body's biological clock. When the animal is infected, the virus acts as a vehicle depositing the telomerase gene in the cells.

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In 2007, Blasco's group proved that it was feasible to prolong the lives of transgenic mice, whose genome had been permanently altered at the embryonic stage, by causing their cells to express telomerase and, also, extra copies of cancer-resistant genes. These animals live 40% longer than is normal and do not develop cancer. The mice subjected to the gene therapy now under test are likewise free of cancer. Researchers believe this is because the therapy begins when the animals are adult so do not have time to accumulate sufficient number of aberrant divisions for tumours to appear.

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As Blasco says, "ageing is not currently regarded as a disease, but researchers tend increasingly to view it as the common origin of conditions like insulin resistance or cardiovascular disease, whose incidence rises with age. In treating cell ageing, we could prevent these diseases".

You'll have to wait for the paper to show up at the EMBO Molecular Medicine website to get more details on the lifespan data, degree to which cancer is removed from the picture, and what type of mouse is being used here - e.g. are they using the transgenic enhanced p53 mouse as a baseline? That shouldn't take too long, and it is an open access publication so we'll all have a chance to read the details.

As an aside, aging defined as a disease is a topic that crops up frequently - but only because of the structure of medical regulation. Regulators in the US, for example, will only approve medical technologies for named, defined diseases. Aging is not on their list, but the problem is not that fact, but rather that a list of what is permitted and an organization to enforce it even exists in the first place.

The employees and appointees of the US Food and Drug Administration have caused an incredible destruction of value and progress over the time that the agency has existed. Their regulatory policies become ever more onerous with each passing year, as unaccountable bureaucrats follow their incentives: nothing good can happen to their careers as a result of approving new technologies, and nothing bad tends to happen to their careers as a result of making it really, really hard to bring new medicine to the clinic. So of course you wind up with an organization whose members collectively pay nothing more than lip service to their declared mission, while working to make sure that medicine stays moribund in a slow-motion stasis.