Fight Aging!

This flashy popular press article in the modern style of scrolling illustrates an important point: that it is actually quite difficult for newcomers to build a coherent picture from the varied claims and lines of research taking place in the field of longevity science. The thing that they are missing, and which takes some time to put together for yourself, is enough of an understanding of the underlying biology to make estimates of likelihood of success for given project versus the plausible scale of the outcome. Will it produce a lengthening of life or postponement of age-related disease, and for how long? Absent this understanding, most journalists tend to put all of the various work at the same level of priority and interest, and thus assemble an article from a more or less random sampling of the field, but this simply isn't the case. For example, the work on developing metformin as a way to slow aging is both unlikely to produce reliable outcomes, based on the animal data, and those outcomes will be small even if successful. The same could be said of pretty much all of the current pharmaceutical approaches that aim to alter the operation of metabolism to slow down the progression of aging - but even in that category, some, like mTOR inhibitors, are far more plausible than others. In comparison, methods of repair that remove damage and waste in tissues, like senescent cell clearance, should be a much more reliable and effective means of turning back aging, producing actual rejuvenation. These are very different things, but few journalists will have the necessary background to explore this point.

The most outspoken opponent of death by aging in the scientific community is probably Aubrey de Grey. In his mind, aging is unhealthy; a collection of undesirable side effects of being alive. He likens aging to malaria because it kills a lot of people. If you could cure it, wouldn't you? There is a growing cohort of well-credentialed scientists investigating radical life extension: geneticist Craig Venter, one of the first to sequence the human genome; biochemist Cynthia Kenyon, who discovered that a mutation in a single gene doubled a worm's lifespan and is now vice president of aging research at Google sister company Calico; and molecular biologist Bill Andrews, who led the team that discovered the human gene for telomerase, an enzyme considered critical in aging. Their promises include keeping 90-year-olds as healthy as 50-year-olds, as the Virginia-based Methuselah Foundation says; extending life to 150 years, as Andrews says; and being biologically 25 years old indefinitely, as de Grey says. We're taught that death is natural and that trying to escape it is wishful lunacy. However, these researchers have made tangible discoveries. They've published studies in highly respected journals and attracted serious amounts of funding. When they say it's possible to live longer, and maybe forever, it's tempting to believe them.

Every few months, scientists will come out with a new finding that shows how a very specific set of changes slowed down some aspects of aging in animals. Of course, each study is more insightful when viewed as part of the body of anti-aging research as a whole. To understand what researchers have accomplished in this area, it's helpful to understand what "aging" means in a scientific context. Specifically, aging refers to the time-related degradation or decline of the bodily functions necessary for survival. As we age, changes occur in our bodies on a cellular level that affect not just our heart and lungs but also our muscles and our nervous system. These changes affect all of the different systems in our bodies. And each of these systems individually begins to work a little less well as we get older, and gradually that produces the burden of dysfunction that ultimately results in disease, disability, and eventually death. We also now understand that biological age doesn't always correspond to clock age. Imagine a pair of twins: One drinks too much, eats poorly, rarely gets enough sleep, and never exercises, while the other does the opposite. The first twin is likely to age faster and develop more of those age-related diseases.

The key lies with what scientists call signaling, or how cells communicate to govern basic functions like cell repair and immune response. While errors in cell signaling can cause autoimmune diseases, diabetes, and cancer, it also turns out that modifying signaling pathways can also slow aging, at least in animals. Researchers have identified two age-related signaling pathways: the Insulin/IGF-1 signaling pathway, which is linked to growth and metabolization, and the Target for Rapamycin or TOR, which in addition to growth regulates how cells move, and replicate. The deeper you get into anti-aging science, the more you'll see these acronyms. If we can slow down that biological clock enough, the thinking goes, we could delay the onset of old age and the diseases that come with it. Centenarians, humans that manage to live to 100 years and beyond, are more likely to carry mutations that reduce the activity of the IGF-1 receptors than those who die younger. At the same time, similar studies in yeast have shown that if you genetically alter TOR signaling pathways so that they communicate less, the yeast also lived longer. In total, the research suggests if you can find ways of calming down these signaling pathways you might be able to slow down aging.

One way of reducing signal TOR pathways is unpleasant if you enjoy eating. Studies have shown that mice fed 65 percent less food lived up to 60 percent longer. Thankfully, researchers have found other interventions, that work on the same pathway. Rapamycin, an anti-rejection drug used by kidney transplant patients, has increased lifespan in mice by up to 14 percent; low-dose Aspirin increased worm lifespan by 23 percent. A national clinical trial called Targeting Aging with Metformin, or TAME, to test Metformin's anti-aging effects in humans has received FDA approval. "What we want to show is that if we delay aging, that's the best way to delay disease."

Link: https://theoutline.com/post/902/the-case-for-defeating-death