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    Efficacy Challenges

    What Does Longevity Mean to Formulators?

    ...

    What Does Longevity Mean to Formulators?
    Longer life spans don’t equate to healthier skin...or a better quality of life!
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    Paolo Giacomoni, PhD, Insight Analysis Consulting01.03.20
    The best way not to get old is to die young.

    That’s hardly a sentence to put on an anti-aging cream label! Nor is it a valid scientific statement! Despite its brevity, it harbors two conspicuous misconceptions: it assumes that juvenescence and senescence are separated by an edge and it confuses longevity and aging.

    The first one would validate the preposterous expression “premature” aging, an expression that implies the existence of a moment in life, before which aging is not “normal.” Indeed, aging starts at birth and is defined as accumulation of damage. When we want to describe the consequences of excessive exposure to aging factors such as solar radiation, oxidative bursts, hormonal imbalance, cold and psychological stress, we should say “accelerated” aging, not “premature” aging.

    The second misconception implies that aging cannot be separated from longevity and this is simply not true. For example, two regions of the skin of one individual can have accumulated different amounts of damage and have, therefore, aaged differently despite having been around for exactly the same number of years.

    It is therefore necessary to try and give a precise definition of longevity.

    For animals and insects, longevity is understood as the time interval between birth and death. According to social and environmental conditions, individuals of a same species can have lives of different duration. Gerontologists speak of average life (aka life expectancy), which must not be confused with maximum lifespan. Human populations with high child mortality and high incidence of infections will have shorter life expectancy than populations with well-developed hygiene and medical technologies. In the West, at the beginning of the 21st Century, life expectancy is about 78 years for males and about 83 years for females (76 and 81 in the US; 81 and 84 in Sweden; and 80 and 85 in Italy) while the maximum life span, that is well above 100 years, has not changed since the time of the ancient Scientists try and find ways to achieve successful aging; that is, aging without age-associated diseases, in the quest of “adding life to years, not years to life.”

    Successful Aging

    Others seek to prolong life span, regardless of whether the individual will be constrained to bed or wheelchair. Greek mythology already discussed this issue with the legend of Tithonos. According to the myth, a goddess obtained eternal life for him without asking for eternal youth. The devil grew so old that he eventually disappeared, and only his voice was left.

    The myth concludes that eternal life without eternal youth is a curse, not a blessing...and yet, the quest for interventions to prolong life span is actively undertaken. One such intervention is caloric restriction, stemming from the observation that lab mice fed a limited amount of food per day (that is, calorically restricted) live longer than mice in a group fed ad libitum. Still, scientists seek to know whether it is caloric restriction that increases maximum life expectancy or excess calories that does indeed reduce it.

    In addition to studying animals, scientists study mono-cellular organisms, which can duplicate a certain number of times before losing their reproductive capability. This phenomenon is a common feature in yeast, paramecium and other unicellular higher organisms as well as in normal human cells in culture. It has been agreed in the academic world that the number of duplications a cell can undergo in certain conditions is its life span. This number is controlled by several parameters, and studies on cell duplication have enabled scientists to learn about biochemical mechanisms in these cells and obtain guidance in human organs.

    In yeast, mutations in a gene called Sir 2 are associated with more frequent duplications. Human cells carry several genes analog to Sir 2, and with a certain lack of imagination, these genes have been called sirtuins. Today, we know sirtuins are involved in several mechanisms controlling cellular metabolism, energy production and cell duplication.

    There is no evidence whatsoever, though, that sirtuins play a role in prolonging the life span of the human body. When sirtuins were advertised as longevity genes and, on the basis of misinterpreted results, sirtuin activators such as resveratrol were said to mimic caloric restriction, the scientific journal Nature1 published three sobering articles on the subject, inviting scientists to cool down before solving the longevity question.

    Longevity & Skin Care

    What does all this bring to skin care? Thanks to the studies on sirtuins, we have learned quite a bit about the metabolism of skin cells and about the role of vitamin B3 analogs. When it comes to human epidermis, we know that after duplication of a cell of the basal layer, one of the daughter cells remains in basal layer and the other enters a process of differentiation that lasts about three weeks, during which it “moves” from basal layer to horny layer and eventually shed.

    What is the life span of a normal human keratinocyte in a normal human epidermis? After duplication, the daughter cell left on the basal layer will duplicate once a day for all the duration of the life of its “owner” whereas the one having started the differentiation process will not duplicate and will be around (I do not dare write “will live”) for three to four weeks.

    When it comes to longevity, it is always better to make it clear whether one speaks of “real” longevity of an individual or of “duplicative” longevity of a cell, and when it comes to keratinocytes in a healthy epidermis, well, the modification of its longevity is not really the concept we want to put forward to advertise the efficacy of a skin care product. 

    Reference
    1. Nature, March 23, 2010.


    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.
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