Logo - Rejuvenal
Research
Search on longevity
Men grow old, pearls grow yellow; there is no cure for it.—Chinese proverb.
The quest for the fountain of youth is as old as human kind. By comparison, the biological study of agerelated illnesses began yesterday. After all, until quite recently in our history, most people didn’t actually manage to grow old, so there wasn’t much point in worrying about it. Genetic malfunction, microbial and virological assault, environmental catastrophe, and our longstanding inclination to kill one another usually swept us from the stage long before we had a chance to sample any of the mixed blessings of growing older: midlife crises, arthritis, enjoying avocational passions built up over decades, seeing grandchildren grow up.
Life expectancies
Public hygiene, relatively healthy diets (well, for some of us), and fewer wars, coupled with the discovery of antibiotics and other medical advances, have worked wonders on our average life expectancies. In the United States, for example, it has gone from about 47 years in 1900 to about 77 years in 2000. And as the size of the aging population in developed countries has increased dramatically so, too, has our interest in understanding exactly how and why we age and what we might possibly do to live a lot longer— and better—than the actuarial tables now say we should.
Homo sapiens; a machine?
Not surprisingly, theories and metaphors about how the human body works, falls ill, and ages have often leaned heavily on the prevailing technology of the age in which they are dreamed up. Steam engines, hydraulic systems, switchboards, and computers have all figured prominently in the language used to describe human physiology. More recently, biologists have been applying classic engineering reliability theory to the problem of aging. What could you, a member in good standing of the species Homo sapiens, possibly have in common with the workings and systematic failings of electronic systems?
Theory of aging
Quite a lot, according to Leonid Gavrilov and Natalia Gavrilova, the chief proponents of the reliability theory of aging. Their theory begins with the provocative idea that we are not born in an optimal condition and that it goes downhill from there. We are born with numerous “faulty” parts and connections that are generated during embryonic development, they say. Then, starting at around age 10, accumulated genetic mutations and environmental damage cause our machinery to start breaking down. Happily enough, our bodies compensate for these defects over our lifetimes by being made up of an enormous number of redundant components, which we call cells.
Centenarian; rule or exception?
Eventually, our life-saving redundancies are used up, at which point one or more of our developmental flaws gets the better of us and we become vulnerable to disease and die. The Gavrilovs are enthusiastic supporters of “engineered negligible senescence” and foresee a not-too-distant future in which aging will be controlled and human life spans extended dramatically. In this worldview, the person who lives to be more than 100 years old could be the norm rather than the exception in the next few decades. And while there’s still quite a gap between mathematically describing the root causes of aging and finding ways to treat these causes—rather than their ravaging symptoms—the Gavrilovs’ work is an important contribution to a young field.
Signal pathway of insulin and insulin-like growth factor 1 (IGF-1) as a potential regulator of lifespan
Chistiakova OV. Zh Evol Biokhim Fiziol. 2008 Jan-Feb;44(1):3-11.
The experimental material accumulated for two decades allows concluding that regulation of lifespan has hormonal control based on the evolutionary conservative insulin/IGF-1 receptor signal pathway. Data obtained on the commonly accepted models of longevity - nematode Caenorhabditis elegans, Drosophila Drosophila melanogaster, and rodents - demonstrate that reduction of the insulin/IGF- 1 signal pathway leads to an increase of the lifespan. There is shown involvement of the longevity mechanism of a large group of genes whose products perform control of metabolism, alimentary behavior, reproduction, resistance to oxidative stress. Discussed in this review are current concepts of the insulin/IGF-1 signal system as a regulatory "longevity module" and of its possible role in prolongation of life in the higher vertebrates, including human.
Extended longevity and insulin signaling in adipose tissue.
Klöting N, Blüher M. Exp Gerontol. 2005 Nov;40(11):878-83. Epub 2005 Aug 25.
Department of Internal Medicine III, University of Leipzig, Leipzig, Germany.
Caloric restriction and leanness have been shown to increase longevity in organisms ranging from yeast to mammals. Adipose tissue seems to be a pivotal organ in the aging process and in determination of lifespan.
We have recently shown that fat-specific disruption of the insulin receptor gene is sufficient to increase lifespan in FIRKO mice, suggesting that reduced adiposity, even in the presence of normal or increased food intake, can extend lifespan. The model also suggests a special role for the insulin-signaling pathway in adipose tissue in the longevity process. Reduced fat mass has an impact on the duration of life in several other model organisms.
In Drosophila, a specific reduction in the fat body through overexpression of forkhead type transcription factor (dFOXO) extends lifespan. Furthermore, sirtuin1 (SIRT1), the mammalian ortholog of the life-extending yeast gene silent information regulator 2 (SIR2), was proposed to be involved in the molecular mechanisms linking lifespan to adipose tissue.
In the control of human aging and longevity, one of the striking physiological characteristics identified in centenarians is their greatly increased insulin sensitivity even compared with younger individuals. The effect of reduced adipose tissue mass on lifespan could be due to the prevention of obesity-related metabolic disorders including type 2 diabetes and atherosclerosis.