Preventing Aging the Same as Staying Young?

So my wife alerted me to this interesting but reference-free article about the prospect for an anti-aging drug, Metformin by name. Human studies might be coming as soon as next year, the author excitedly announces. We could live to be 120 years old and even stay healthy.

Who doesn’t want to stay young? Well…. I stay young by doing things like caving in to pressure and buying a smartphone after years of owning a flip phone.

smartphone with clip

Does my ginormous but practical Otter Box case and belt clip (NOT a “holster”) make you burn with envy? Pay no attention to that chapstick.

Intrigued, I had a quick look at PubMed to see if this on the level. I found an article by Castillo-Quan et al about drugs for slowing down aging and one of the keywords was, in fact, Metformin [1]. The authors say, “According to the UN Population Division, currently 800 million people are over the age of 60 years and comprise 11% of the world’s population. By 2050, this percentage will double to 22%, meaning two billion people worldwide will be 60 years of age or more.” And they remind us that we don’t stay healthy as we age.

You can try to read the entire article ( I double dog dare you; it’ll age you pretty fast), although I have not done more than skim it looking for what interested me–Metformin and telomere attrition and activating telomerase, among other tidbits. Taking care of our telomeres (cellular components important for the maintenance of cell repair) turns out to be important and I recall reading about how mindfulness meditation may protect and prevent damage to telomeres. I didn’t see that Castillo-Quan and colleagues mentioned that anywhere.

Anyway, the authors point out that telomere shortening correlates with aging and activating telomerase (an enzyme that promotes the health of telomeres) can delay aging.

But because we’re a society which values medicines, we need a pill to postpone aging. Believe it or not, Metformin, an oral hypoglycemic (antidiabetic) drug, has extended the life span of certain worms and mice. This has been also been associated with “…reduced cholesterol levels (total cholesterol and LDL), improved glucose tolerance and locomotor ability, increased antioxidant defense, and reduced markers of inflammation.”

There was no mention of upcoming studies of using Metformin to slow down aging in humans in the Castillo-Quan paper. In fact, they cast doubt on its potential effectiveness, “…the only study to report beneficial effects of metformin on mammalian life span showed that the effect was quite small, which begs the question as to whether metformin acts to modify longevity or to improve health by acting on disease processes.”

However, what may be just as interesting is the use of lithium, a drug used to treat Bipolar Affective Disorder, to promote another process which might help stave off aging, autophagy, which is a normal physiological process in the body that is associated with the destruction of cells in the body. It maintains homeostasis by protein degradation and turnover of destroyed cell organelles for new cell formation. During cellular stress, autophagy is increased. Lithium also extends the life span of worms and fruit flies and has been reported to modulate neurodegeneration.

Valproate, another drug used to treat bipolar disorder, acts similarly to lithium.

It sounds more likely that psychiatric drugs rather than Metformin could prolong life although judging from the number of patients I see who develop toxicity from lithium and end up medically hospitalized, I doubt it.

The authors also talk about “polypills.” A polypill combines two or more drugs into one package, so to speak. The concept was introduced by heart disease researchers who are currently studying whether a combination of a statin, three half-standard dose antihypertensives, folic acid, and aspirin would reduce ischemic heart disease and stroke events by more than 80%.

If that sounds far-fetched, just remember that a drug company is selling a polypill product called Nuedexta, FDA-approved combination of quinidine and dextromethorphan for treating pseudobulbar affect–although indication creep is occurring as we speak and it’s also being studied for use in treating agitation in dementia and more.

So will we be able to take a pill to slow down aging? As the authors caution, we’d better have a good definition of what we mean by “aging.” And has anybody thought about what might happen to Social Security if everybody starts living to 120? Would I outlive my retirement savings?

Would I upgrade my smartphone?

Reference:

  1. Castillo-Quan, J. I., et al. (2015). Chapter One – Genetics and Pharmacology of Longevity: The Road to Therapeutics for Healthy Aging. Advances in Genetics. J. C. D. Theodore Friedmann and F. G. Stephen, Academic Press. Volume 90: 1-101.
    Abstract Aging can be defined as the progressive decline in tissue and organismal function and the ability to respond to stress that occurs in association with homeostatic failure and the accumulation of molecular damage. Aging is the biggest risk factor for human disease and results in a wide range of aging pathologies. Although we do not completely understand the underlying molecular basis that drives the aging process, we have gained exceptional insights into the plasticity of life span and healthspan from the use of model organisms such as the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Single-gene mutations in key cellular pathways that regulate environmental sensing, and the response to stress, have been identified that prolong life span across evolution from yeast to mammals. These genetic manipulations also correlate with a delay in the onset of tissue and organismal dysfunction. While the molecular genetics of aging will remain a prosperous and attractive area of research in biogerontology, we are moving towards an era defined by the search for therapeutic drugs that promote healthy aging. Translational biogerontology will require incorporation of both therapeutic and pharmacological concepts. The use of model organisms will remain central to the quest for drug discovery, but as we uncover molecular processes regulated by repurposed drugs and polypharmacy, studies of pharmacodynamics and pharmacokinetics, drug–drug interactions, drug toxicity, and therapeutic index will slowly become more prevalent in aging research. As we move from genetics to pharmacology and therapeutics, studies will not only require demonstration of life span extension and an underlying molecular mechanism, but also the translational relevance for human health and disease prevention.

Keywords

  • AMPK;
  • Antiaging;
  • Aspirin;
  • Autophagy;
  • Demography;
  • Dietary restriction (DR) mimetic;
  • Drug;
  • Healthspan;
  • Ibuprofen;
  • Insulin/IGF-1 signaling;
  • Life expectancy;
  • Life span;
  • Metformin;
  • miRNA;
  • mTOR;
  • NRF-2;
  • Polypill;
  • Proteasome;
  • Rapalog;
  • Rapamycin;
  • Resveratrol;
  • Target of rapamycin;
  • Translation
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