Too often, the words aging and longevity are used interchangeably, as if they meant the same thing—but nothing could be further from the truth. Indeed, if aging and longevity were synonyms, then the best way not to grow old would be to die young. As a matter of fact, longevity and aging are two distinct concepts. First and foremost, longevity is a property of the individual organism. In contrast, aging is a characteristic of the organs as well as of the extracellular matrix of that organism.

Longevity Defined

For individuals belonging to the animal kingdom, longevity is defined as the time interval between birth and death. For specific groups of individuals, one can speak of maximum lifespan (about 120 years in humans) and of life expectancy (that is, the average life lived by all the individuals in a group) in a well-defined time frame. It must be noted that life expectancy is neither the maximum lifespan nor the lifespan of the regular adult. To give an example, a life expectancy of 50 years for a defined human population could be the consequence of a 33% mortality at birth and of a surviving population living between 74 and 76 years. 

In human populations, hygiene and antibiotics have historically been the two major factors for large increases of life expectancy. In the 19th and early 20th centuries, they dramatically reduced death at birth and curbed the effects of infectious diseases. In more recent years, widespread vaccinations led to the eradication of several viral diseases and provided a non-negligible contribution to the increase of life expectancy. Yet, these factors did not have an effect on maximum lifespan or on the usual lifespan (longevity) of regular individuals. After all, a regular guy in ancient Rome could live into his eighties, as can a regular gal today.

In the search for the Elixir of Long Life, scientists try treatments to increase the (maximum) lifespan. Conducted on humans, such research could be excruciatingly long. Instead, scientist study the effects of their treatments on mice, which live about two years. One of the treatments consists of caloric restriction. Rather than getting fed ad libitum, as are the mice in the control group, the test group of mice receives a determined food with a limited amount of calories. Lo and behold, the test group has an average lifespan longer than the control group. 

Hooray! Calorie-restricted mice live longer than ad libitum-fed mice! Are we sure? Couldn’t it be that the ad libitum fed mice live shorter lives than the caloric restricted ones? What if excess food were to reduce lifespan? What is the relevant control? How long does a mouse live in the wild when it is not used as food by a nearby cat?

Aging Defined

Aging is a characteristic of the organs (liver, heart, lungs, spleen, kidneys, skin, arteries…) and of the extracellular matrix (bones, cartilage, elastic fibers, ground substance, vessel walls…) of an individual. According to the behavior of their owner, organs and extracellular matrices can age more or less quickly. The aging of some organs, such as the liver or kidneys, can have a negative effect on the owner’s lifespan. We do not have data indicating that aged skin affects longevity, with the caveat that, properly speaking, melanoma is not a skin cancer since melanocytes originate from the neural crest and not from the endoderm or the ectoderm.

Aging has been defined as the accumulation of molecular modifications over time. This definition allows one to quantitatively test if a treatment can be considered to be anti-aging. For instance, one could apply UV on a zone of the skin and measure the presence of carbonylated proteins. Next, treat half of the zone with a treatment and leave the other half untreated. Then, measure again the carbonylated proteins. In some instances, the organ itself can remove the modifications, also called damage, and resynthesize a new component to replace the damaged one. In this process of repair and remodeling, the organ and mainly the extracellular matrix, lose their youthful characteristics and acquire an aged phenotype. A typical example is given by skin chronically exposed to solar radiation. It is sagging and elastotic, not because it has lost collagen, but because the dermal collagen is no longer organized in orderly elastic fibers. Therefore, it cannot provide elasticity and resilience. 

Interventions

In the quest of interventions to reduce the rate of aging or to improve longevity, some scientists choose to target the aging of the cells. Doing so, they must define the longevity of a cell. They chose to define cell longevity as the number of duplications a cell can perform before reaching senescence; that is, the status of incapability to duplicate. Of course, we’re counting cells in culture—it is quite a task to measure how many duplications a cell can perform in vivo! 

For instance, yeast can duplicate about 12 times. This number can be increased by specific treatments or by introducing specific mutations. Normal, cultured human fibroblasts can duplicate about 50 times. Normal, cultured human keratinocytes can duplicate about 20 times. These numbers are much smaller than the number of duplications of a keratinocyte in vivo. Researchers estimate a keratinocyte duplicates once a day every day during the life of the owner—up to 100 years or more. 

In certain instances, mainly when mutations affect cell functions and provoke age-associated impairments or diseases, this approach is promising. In other instances, as in the skin, signs of aging can be the consequence of impaired cellular function. For example, age reduces filaggrin production. That leads to dryness and itchiness, and mainly of repair and remodeling of the extracellular matrix. The loss of elasticity, the thinning, the sagging, the loss of water retention, are all consequences of a damaged extracellular matrix. Wrinkles are the result of nerves pulling thin and sagging skin to keep it around the face. Wrinkles are a neuromuscular as much as a cutaneous problem, and Botox is there to prove it. Interventions to reduce the rate of aging of the skin can be reasonably conceived, discussed and put to work. Interventions to increase the longevity of the skin are less likely to succeed, unless we consider the verbal locution “skin longevity” to mean the “duration of the optimal status of skin physiology!”

Paolo Giacomoni, PhD

Insight Analysis Consulting

paologiac@gmail.com
516-769-6904

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.