Is Aging a Curse…or a Choice?

When was chemistry born? What about quantum physics? Among all the sciences, only the biology of aging has an exact birth date—August 11, 1986. That was the first day of the Gordon Conference. There, American scientists from fields as diverse as bacteriology and human pathology gathered to discuss aging—not as a disease—but as a biological phenomenon. One eye-catching bit of information was that Paramecium, an asexual monocellular organism that does not exchange genetic material to multiply, undergoes a well-defined number N of divisions before “dying.” The other eye-catching information was that, when two Paramecia “have sex,” the count of divisions they performed before sex is erased and the two Paramecia start over again to have N divisions before “dying.” A few years later, in 1991, 12 European scientists were among those gathered in Ancona, Italy for a symposium on aging. There, they decided to create the European Network for the Study of the Biology of Aging. 

In the international arena, there were those asking: “Would you like to live 300 years?” and those insisting that “Living 1,000 years is easy, one just has to double the rate of repair!” On the other side of the argument, there were those explaining that, as far as the European Network was concerned, the goal is to add life to years, not years to life!

Some History & Mythology

Perhaps the first question to be tackled was how to define aging: people were not satisfied with the tautologous definition that aging is the loss of the characteristics of youth. To complete Leslie Orgel’s belief that the process of aging arises due to mutations acquired during the self-replication process, aging was defined as accumulation of damage.¹ Molecular damage, when accumulated, induces observable, age-related impairments such as wrinkles and kidney failure, age spots and osteoporosis. 

This definition was inspired by the Greek myth of Tithonos. His lover was Eos, goddess of the dawn. Tithonos asked Eos for immortality, but he forgot to ask her for eternal youth. As a result, poor Tithonos grew older and older, and ended up worn and torn until he disappeared altogether. So, if eternal youth is restoring the status quo ante every time there is a modification in the body,² aging can be advantageously defined as accumulation of damage. This is fortunate because such a definition allows one to perform quantitative measurements relative to the anti-aging properties of treatments by assessing the level of a well-defined damage before and after the treatments. 

A lot of attention was devoted to the effect of oxidative stress on the process of aging. Indeed, the oxidative model of aging was very fashionable and deserved being examined accurately. For instance, it had been observed that the lifespan of different mammals is inversely correlated with the specific metabolism (metabolism per unit mass of tissue), as shown by the different lifespan of mice and elephants, who vary greatly in size and have very different, specific metabolisms. To test this hypothesis, the lifespan of mice fed ad libitum (high metabolism) was compared with the lifespan of mice kept under caloric restriction (low metabolism). It turned out that calorically restricted mice lived longer. Nobody asked the question, though, whether it is the calorically restricted mouse who lives a longer life, or whether it is the ad libitum fed mouse who lives a shorter life! 

It was pointed out that all the factors known to accelerate aging shared as a common mechanism—the capability to trigger an inflammatory response. From cigarette smoke to ultraviolet radiation; from stretching to exposure to cold; from neuropeptides to bacterial infections; and from hormonal changes to anoxia—all these factors of aging have the capability of inducing the expression of the Inter-Cellular Adhesion Molecule 1 (I-CAM 1) that recruits immune cells from the blood vessels. To reach the damaged cell and remove it, immune cells degrade the extracellular matrix via a triple oxidative burst that damages and disorganizes the structural elastic fibers. This role of the inflammatory process was first pointed out as a major mechanism for skin aging³ and was later observed to occur in several age-associated disorders such as rheumatoid arthritis⁴ and even in Alzheimer’s Disease.⁵ The importance of this mechanism is underscored by the name of a European program of research on aging, appropriately called Inflamage.

Must We Really Age?

For years, members of the European Network for the Study of the Biology of Aging explored the possibility that aging could be programmed. That could happen according to the Disposable Soma Theory; i.e., the theory of the dispensable body. Proponents invoked the theory of evolution and postulated that the individual faces a trade-off in resource allocation, between somatic maintenance and reproductive investment; that is, between the lifespan of the individual and the size of the progeny. If this were true, then one should look for the molecular mechanisms selected in the course of evolution, to allow females to make lots of babies and to die relatively young. This seems not to be the case, at least in humans, where female outlive males sometimes by “two-digit” lifespan differences. Wikipedia summarizes clearly and concisely that one of the main weaknesses of the disposable soma theory is that, in addition to contradictory results in field experiments, it does not propose any specific cellular mechanisms to which an organism shifts energy to somatic repair over reproduction. Instead, it only offers an evolutionary perspective on why aging may occur due to reproduction. 

I would add that there is a lexical confusion in the science of biology of aging; some authors consider aging synonymous with longevity and others point out that longevity is a consequence of aging. For instance, when an organ ages too quickly, then the individual with the aged organ might die while still being chronologically young. 

Must we really age, or do we age because we want to? Let me point out that the simple fact of breathing produces superoxide and that superoxide can damage mitochondrial DNA, leading to impaired production of energy and eventually to a slow accumulation of damage. We should keep in mind that what is relevant is the rate of accumulation of damage: if we could reduce it by a factor of two, we could expect the first wrinkle at the age of 60, not at the age of 30. So, the rate of appearance of the visible damage, from age spots to liver cirrhosis, will depend on us being sun worshippers or ethanol junkies. The same holds for cigarette smokers, psychologically-stressed individuals, winter sports addicts and anyone else who forgets that moderation in all things is the key to successful aging.

References

1. Giacomoni, PU (1995) Radiazione ultravioletta, invecchiamento e blebs. 
2. Giornale di Gerontologia, 43 : 209-210
3. Giacomoni, PU (1992) Aging and Cellular Defence Mechanisms. 
4. Ann NY Acad Scie 663 : 1-3
5. Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. 6. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement (N Y). 2018 Sep 6;4:575-590. doi: 10.1016/j.trci.2018.06.014. PMID: 30406177; PMCID: PMC6214864.

Paolo Giacomoni acts as an independent consultant to the skin care industry. He served as Executive Director of Research at Estée Lauder and was Head of the Department of Biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents. He is presently Head of R&D with L.RAPHAEL—The science of beauty—Geneva, Switzerland. His email is paologiac@gmail.com