Being able to reverse or slow down the degenerative processes that seem to come along with increased age is a long standing human aspiration; and this search has provided a consistent focus for decades of scientific research on aging and longevity. But it has only been in recent years that the idea of replacing palliative treatments that only suppress symptoms can be replaced with anti-degenerative medicines that repair and/or reverse causes as being seen as more than just fanciful hopeful fruits of a mere pipe dream.
This long sought after paradigm shift stems from recent research that demonstrates a few biological root causes underpin almost all of the diseases of old age. These discoveries bring about opportunities to address a wide range of illnesses with simultaneous treatment that target single biological mechanisms; for the first time aging appears to have become druggable.
One of the leading causes of age related changes appears to be accumulation of senescent cells. Unfortunately this process is a consequence of evolution that comes into play when organisms outlive a normal reproductive age or are subjected to a damaging environment; as cells become senescent the no longer divide, but they are not cleared away and typically behave in a way that will damage tissues around them, earning the nickname zombie cells.
Much of the gerontological community considered these cells to be a symptom rather than a cause of age related decline for years, until recent groundbreaking research has shown that removing these zombie cells from mice prevents normal aging and reverse many of the symptoms, proving that these cells cause aging and provide potential opportunities to develop a cure.
Building on the positive effects of removing zombie cells from mice has revealed it can be extended to myocardial infarction, Alzheimer’s disease, and metabolic dysfunction. The ever present challenge is to now translate these positive findings into treatments in aging humans. Major investors can see the promise of the research and are joining the search to find ways to either, remove, kill, or rejuvenate senescent cells, and exciting progress has been made.
Among the exciting progress when combined dasatinib and quercetin have been shown to improve both health and lifespan in mice. Early results from clinical trials using this cocktail have demonstrated for the first time, showing alleviation of physical dysfunction in patients with idiopathic pulmonary fibrosis, which currently has no known effective treatment. Dasatinib has side effects so this treatment will likely be restricted to the most seriously ill, but despite this the trial provides hope that a more palatable second generation of similar drugs may be developed by medicinal chemists.
Resveratrol may be an alternative strategy to rejuvenate these zombie cells, as in lab settings it was shown to restore the molecular fingerprint and growth of senescent cells to that of normal and youthful cells. Small synthetic modifications were also demonstrated to be able to tune the effects achieved adding to the hope that a medicinal chemistry approaches to the problem are likely to be successful.
Fisetin has also been shown to confer improvements is health as well as a reduction in the senescent cell load in old mice, and is now the subject of clinical trials. Fisetin also interacts with other aging mechanisms such as nutrient sensing which is the biological mechanism that underlies the health and lifespan extending effects of calorie restriction.
While it is not yet fully clear whether simultaneously targeting more than one cause of aging will be completely effective or if it will reveal a new piece of the puzzle that will allow us to integrate the other known parts to morbidity into a coherent whole remains to be seen. But thus far results from research using natural products and existing drugs(senolytics) have been positive, unequivocally showing that small molecules can produce a broad spectrum of anti-degenerative effects.
Anti-aging and longevity drug discovery is starting to move beyond its infancy, and preventative medicine that can revolutionize the 21sy century is on the horizon as being genuinely possible. There may be a need to add synthetic medicinal chemistry into the mix in order to develop safe and effective drugs that can help us all move forward to a healthier and more active future.
Even though future development looks very promising, this will still need to be paired with living a healthy lifestyle which can only be done by following a healthy diet, managing stress, getting enough sleep, and being physically active. Making better lifestyle choices will lessen the body’s burden of inflammation which is the silent root behind many chronic conditions. Maintaining a healthy lifestyle has been shown time after time to naturally lead to longer health and lifespans. Why be content to wait idly by while science presses forward, take steps now to help ensure that you live as long as you can as healthy as possible.
