Aging is at the root of some of the most important human diseases.

What if we could delay the many diseases of aging?

Aging is the single greatest risk factor for much of the disease in the developed world.

Aging leads to dramatic increases in rates of cancer, cardiovascular disease, and neurodegenerative disease (1–3). As the world’s population continues to age, the cost of these age-related diseases, in human suffering and in economic terms, will continue to increase (4).

Work to slow aging itself has the potential to simultaneously delay all of these diseases (5,6,7).

Even in those who never obviously suffer from any of the aging-linked diseases described above: if they otherwise live long enough, aging is what they will die of. Aging affects 100% of the population who live long enough, and to date it is then 100% fatal.

We can greatly alter aging in the lab. Our answers to the question of whether aging is alterable, and to what extent, have evolved very rapidly in recent years. Comparative studies have long pointed out hundred-fold variation in natural lifespan, even among otherwise very similar organisms (8). More recent work in lab-based genetic model organisms, including some of our own models, the budding yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans, as well as the fruit fly Drosophila melanogaster and the mouse Mus musculus, has demonstrated up to 10-fold changes in lifespan from mutations in a single gene (9–15). In many cases, mutations of the same gene greatly extended lifespan in both invertebrate models and in mammals (16-19). This suggests that in aging as in many other biological processes, what we learn in the lab has a good chance of teaching us powerful things about human biology.

Starting from genetic studies, this work has now progressed to identifying drugs that can remarkably extend lifespan in many organisms, including mice (20-23).

Interestingly, many of these genetic changes and drug treatments do not simply drag out the last part of life- rather, they appear to greatly extend the time during which organisms are healthy and youthful (i.e., their healthspan) (24-26).

Starting from findings in simpler models like S. cerevisiae and C. elegans, some of these drugs are now already moving into the testing phase in companion dogs (27, 28) and humans (29).

In the McCormick Lab, we are following several lines of ongoing research to uncover a more complete picture of conserved genes that can affect aging in multiple organisms, including humans. We are using these results to build a deeper understanding of the underlying conserved biology of aging. We are also identifying drug targets, and drugs, that can delay aging in the lab in multiple distantly related organisms. Our hope is that some of these drugs may also delay the onset of age-related diseases, and perhaps aging itself, in humans.

References

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20. Harrison, D. E. et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395 (2009).

21. Miller, R. A. et al. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J. Gerontol. A. Biol. Sci. Med. Sci. 66, 191–201 (2011).

22. Harrison, D. E. et al. Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell 13, 273–282 (2014).

23. Bitto, A. et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. eLife 5, (2016).

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28. Urfer, S. R. et al. A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs. GeroScience (2017).

29. Mannick, J. B. et al. mTOR inhibition improves immune function in the elderly. Sci. Transl. Med. 6, 268ra179 (2014).