Forever young versus the self-destruction of the body

The Daily Beast named 2015 "The Year We Decided to Live Forever". Why? Because the rich people (e.g., Peter Thiel, Sergey Brin, Mark Zuckerberg, etc.) would like to live if not forever, for a very, very long time, and therefore, are ready to fund research on extending human life with millions of dollars.

However, increasing the quality of the years, rather than the number of years, we live might be a better goal. For example, can we increase dramatically the quality of life beyond age of 50? To achieve this, we need to know exactly what causes aging and the associated conditions.


Artistic representation of human age
 
A 2015 study based upon 1554 individuals (including centenarians), established that among all physiological markers, the inflammation score was the best predictor of successful aging at extreme old age (Arai Y, et al. Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians. EBioMedicine. 2(10):1549-58; 2015.) This study confirmed the already established consensus that chronic inflammation is a defining feature of aging, and that inflammation is present in many, if not all age-associated diseases and conditions: Alzheimer’s disease, dementia, cardiovascular disease, multiple sclerosis, diabetes, etc. The increase in pro-inflammatory factors with age has been well documented. Plasma levels of the complement protein C1q were shown to increase with age and to promote age-related MuSC decline by activation of the Wnt signaling pathway (A. S. Brack et al., Science 317, 807–810 (2007) A. T. Naito et al., Cell 149, 1298–1313, 2012). Similarly, beta 2-microglobulin, a component of the major histocompatibility complex, was found to be elevated in the blood of aged mice and to contribute to the age-related decline of the organism (L. K. Smith et al., Nat. Med. 21, 932–937, 2015).

There are many hypotheses about the association between age and inflammation. However, scientists are still unsure whether inflammation causes aging, or vice versa, aging causes inflammation.

One of the best explanations (with most logic in it) is that inflammation does cause aging, and inflammation is the result of the immune response to the mutations that we accumulate with age. The more we live, the more mutations we accumulate. Some of these mutations could  contribute to cancer development, but some do not. However, all mutations that change our proteins sufficiently to induce immune response may contribute to the increasing levels of inflammation in the body. As a result, our own immune system starts attacking and damaging our own body.

To slow down, but not eliminate entirely, the accumulation of mutations (and therefore, the ensuing inflammation and aging) one needs to live a life free of mutagens (as a part of a healthy lifestyle). Of course, we cannot be entirely free of mutagens, but we can eliminate the most obvious ones (e.g., smoking, alcohol, processed meat, etc.).   

Another complimentary approach of evading fast aging is this of slowing down the division of the adult stem cells in our bodies. This is important, since most mutations accumulate during stem cell divisions (by the way, the attrition of telomeres also happens during cell division), and these stem cells can give rise to many other cells (stem cells, progenitor and differentiated cells of the body). 

Drosophila (fruit fly)

The only way that we might be able to slow down stem cell divisions in our body is through periodic fasting and calorie restriction. The more we eat, the faster the adult stem cells divide, and the faster we age. There is a direct evidence that well-fed state results in more stem cell divisions at least in studies of fruit flies.