Carnosine is believed to rejuvenate the skin
normal cells, replicative senescence results from loss of telomeric repeats after
several rounds of cell division. This generates a DNA-damage signal that activates
p53. Some anticancer drugs induce cell senescence by inducing this DNA-damage
response in both normal and malignant cells. Carnosine, in contrast, has a striking
ability to reverse the signs of aging in skin cells (fibroblasts) approaching
senescence and to restore normal appearance and extend the life span of skin cells
(fibroblasts). These functions are attributed to carnosine´s effects against
all forms of protein and phospholipid modification. The limited capacity of the
cell to perpetuate itself through division is called the Hayflick Limit.
Hayflick Limit has to do with the mortality of our cells. Most cells regenerate
themselves by dividing to form a pair of new cells. As early as in 1961 Dr L.
Hayflick discovered that cells eventually reach a limit beyond which they cannot
continue to divide. In a now-famous series of experiments, Hayflick demonstrated
that cultured human fibroblasts (connective tissue cells) can divide only about
60 to 80 times. By young adulthood, fibroblasts have 30 to 40 divisions left,
while in old age no more than 10 to 20 remain. When a cell reaches this "Hayflick
Limit" it enters into a twilight state called cellular senescence. Senescent
cells are very much alive, yet they are distorted in both form and function.
human fibroblasts are suitable for cultivation and observation in laboratory.
Cultures of senescent cells cannot be mistaken for younger cells, which are uniform
in appearance and line up in parallel arrays. By contrast, senescent cells exhibit
a grainy appearance and take on odd shapes and sizes. They lose the ability to
organise themselves in a regular pattern. These striking changes are called the
In a remarkable series of experiments, Australian
scientists, led by Dr McFarland, have shown that carnosine rejuvenates cells as
they approach senescence. What is most exciting is the ability of carnosine to
reverse the signs of aging in cells approaching senescence. When the scientists
transferred late-passage fibroblasts to a culture medium containing carnosine,
they exhibited a rejuvenated appearance and often an enhanced capacity to divide.
They again grew in the characteristic whorled growth patterns of young fibroblasts,
and resumed a uniform appearance. But when they transferred the fibroblasts back
to a medium lacking carnosine, the signs of senescence quickly reappeared.
The scientists switched late-passage fibroblasts back and forth several times
between the culture media. They consistently observed that the carnosine culture
medium restored the juvenile cell phenotype within days, whereas the standard
culture medium brought back the senescent cell phenotype. The carnosine medium
also increased life span, even for old cells.
These results have been confirmed
by British investigators, led by professor Alain Hipkiss, who showed that carnosine
actually lengthens the life span of human fibroblast.
They write: "Carnosine
can delay senescence in cultured human fibroblasts and reverse the senescent phenotype,
restoring a more juvenile appearance. As better antioxidants/free-radical scavengers
than carnosine do not demonstrate these antisenescent effects, additional properties
of carnosine must contribute to its antisenescent activity. Having shown that
carnosine can react with protein carbonyls, thereby generating "carnosinylated"
polypeptides using model systems, we propose that similar adducts are generated
in senescent cells exposed to carnosine. Polypeptide-carnosine adducts have been
recently detected in beef products that are relatively rich in carnosine, and
carnosine's reaction with carbonyl functions generated during amino acid deamidation
has also been described. Growth of cultured human fibroblasts with carnosine stimulated
proteolysis of long-labeled proteins as the cells approached their "Hayflick
limit," consistent with the idea that carnosine ameliorates the senescence-associated
proteolytic decline." (Hipkiss et al 2002).
This research team
is a candidate to receive the Anti-Ageing Science Award at Chicago University....
Carnosine's revitalizing effects on cultured
fibroblasts may explain why it improves post-surgical wound healing.
does the skin wrinkle?
Senescent cells, keratinocytes and fibroblasts,
behave in deviant ways and they appear to accumulate with age in human skin. They
generate more metalloproteinase enzymes that break down proteins in the surrounding
extra cellular matrix (the fabric that holds together cells, lymph nodes and blood
vessels). They also generate adhesion molecules that contribute to hardening of
arteries. Senescent cells express genes that have long-range, pleiotropic effects
- degradative enzymes, growth factors, and inflammatory cytokines. Thus, relatively
few senescent cells might compromise skin function and integrity. Senescent cells
accumulate with age in all organs and tissues, where they resist programmed cell
death (apoptosis) and contribute to age-related degeneration. Moreover, by altering
the tissue micro environment, senescent cells may also contribute to the rise
in cancer that occurs with age.
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