Fight Aging!

By virtue of the fact that very large sums of venture capital, big pharma investment, and public funding have been sunk into the examination of sirtuins in connection with longevity in mammals, I think we'll see a strong sirtuin research contingent in the scientific community for some years to come - and this regardless of the ultimate merits of this work. While there are promising signs that sirtuins may do something useful in terms of enhancing cellular housekeeping, after some years of research we have yet to see any of the promise of slowed aging that looked possible at the outset. See, for example:

• A Possible Reason For Sirtuin Uncertainty
• Critiquing the Sirtuin Model of Calorie Restriction

Research and development always takes longer than expected, but at this point I look at research into sirtuins as an early step forward on a much longer road - a part of the foundations of some later work, and producing little of direct use in and of itself. The newer technologies and newer companies who work on the same strategy of slowing aging via identification of ways to manipulate metabolism will leap over the work of the last five years, producing a hundred-fold more genetic and biochemical data in the process. Biotechnology is advancing so rapidly that each generation of development is made obsolete before it even hits its stride. It will be interesting indeed to see what comes after the present generation of biotech startups like Genescient and Halcyon Molecular.

But back to sirtuins: here is an optimistic open access paper from researchers who do see a bright future for the development of sirtuin-based therapies.

How does aging occur? Can we delay the aging process? These are questions that have been asked for hundreds if not thousands of years.

...

Aging is one of the most fundamental biological processes. It results in a decline in physiological function and an increased risk for pernicious diseases such as cancer. Oxidative stress has been proposed as a major cause of aging, but experimental tests of this hypothesis have been discouraging. Calorie restriction (CR) prevents age-related decline, but there are still gaps in our knowledge of the exact mechanisms underlying this feat. Finally, a tenuous balance exists between aging and cancer, calling for a search for interventions that prevent both aging and cancer. Recent work on the mammalian sirtuin SIRT3 has shed light on these long-standing issues and suggested new approaches to ameliorate the ravages of aging.

You might look back into the Fight Aging! archives for a quick overview of the relevance of SIRT3 to oxidative stress and longevity:

This research group proposes that Sirt3 acts on longevity through increasing antioxidants - we should all be appropriately skeptical, given the very mixed evidence for links between cellular antioxidants and longevity. That said, Sirt3 is located in the mitochondria, and the demonstrations of extended life spans through increased antioxidants have involved targeting those antioxidants to the mitochondria.

When considered in the broader context, a great many lines of research turn to point towards our mitochondria and the damage they suffer over time. All the more reason to direct greater efforts towards nascent mitochondrial repair technologies rather than yet more metabolic tinkering.