Post on 13-Aug-2020
Quale ruolo delle sostanze nutrizionali efunzionali contenute negli integratorialimentari per il paziente anziano
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Ipotesi genetica Ipotesi dei telomeri
Ipotesi immunitaria/infiammatoria Ipotesi dei radicali liberi
PERCHE’ INVECCHIAMO?
Cosa è la Nutrigenomica?• Lo studio delle
interazioni tra I nutrienti del cibo e i nostri geni
• La comprensione di come gli individui sono affetti dalle variazioni del DNA
Energy homeostasis
Nutrient absorption
Cell proliferation
Nutritional factors
Transcription factors
Gene transcription
Nutrients acts as dietary signals
Calorie Restriction (without nutritional deficiency) extends life in all species tested
Eakin F & Witten M Experimental Gerontology 1995, 30: 33-64McCay CM et al. J. Nutrition 1935, 10: 63-79
Sopravvivenza in topi sottoposti a Restrizione Calorica (CR)
100
75
50
25
00 10 20 30 40 50 60
Sop
ravv
iven
za(%
)
Mesi
No CR25% CR55% CR65% CR
Masoro EJ Mech Aging Dev 2005
Saccharomyces cerevisiae longevity genes
Finkel et al. Nature 2009, 460:587-591
• Caloric restriction has been proven to extend the lifespan of a number of species, including mammals
• In yeast, a caloric restriction stimulates the activity of an enzyme referred to as Sir2
• Administering resveratrol to yeast increased Sir2 activity in the absence of caloric restriction and extended the replicative lifespan of yeast by 70%$
Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA.Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.Nature. 2003 Sep 11;425(6954):191-6.
• The French Paradox was the observation that mortality from coronary heart disease is relatively low in France despite relatively high levels of dietary saturated fat and cigarette smoking
• This led to the idea that the regular consumption of red wine might provide additional protection from cardiovascular disease
The French Paradox
controlresveratrol
Valenzano DR, Cellerino A.Resveratrol and the pharmacology of aging: a new vertebrate model to validate an old molecule.Cell Cycle. 2006 May;5(10):1027-32.
Nothobranchius furzeri
Resveratrol treatment prolonged lifespan and delayed the onset of age-related dysfunctions in this fish.
Baur JA, de Cabo R and Sinclair DAResveratrol improves health and survival of mice on a high-calorie dietNature advance online publication 1 November 2006 Department of Pathology, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School
Attivazione Sirtuine
PGC-1α
FOXO ApoptosiInsulina
Biogenesi Mitocondriale
Malattie Metaboliche
Disordini NeurologiciMalattie Cardiovascolari
Resveratrolo
Meccanismo di azione del Resveratrolo
OOH
OHO
A C
B
OH
OH
OH
Phenolic Compounds
Scapagnini G, Colombrita C, Amadio M, D'Agata V, Arcelli E, Sapienza M, Quattrone A, Calabrese V. Curcumin activates defensive genes and protects neurons against oxidative stress. Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):395-403. Institute of Neurological Sciences, National Research Council (CNR), Catania, Italy., Blanchette Rockefeller Neurosciences Institute, West Virginia University, Rockville, Maryland.
CURCUMIN
Low antioxidantCapacity (Catalase, GSH and SOD less than 1/5 compared to liver)
High use of oxygen
Rich in PUFA(polyunsaturated fatty acids)
Areas rich in iron
heme oxygenase 1
ferritin
thioredoxin
GSH transferases
UDP-glucoronosyltransferases
NAD(P)H:quinone oxidoreductase 1
g-glutamylcysteine synthetase
GSH-reductase
catalase
biliverdin/bilirubinCOFe
GSH synthesis
regeneration of ubiquinol and tocopherol
regeneration of GSH and dehydroascorbate
multifunctional roles
regeneration of oxidized thioredoxinand dehydroascorbate
ANTI
OXI
DAN
T AN
D CY
TOPR
OTE
CTIV
E AC
TIO
N
Phase 2 Response Phase 2 ResponseNrf2/keap1/ARE CytoprotectionPhase 2 Response
ANTI
OXI
DAN
T RE
SPO
NSI
VE E
LEM
ENT
(ARE
)O
OR2
HO
OH
OH
R1
HO
Keap1
Nrf2
antioxidant
Chandra V, Pandav R, Dodge HH, Johnston JM, Belle SH, DeKosky ST, and Ganguli M. Incidence of Alzheimer's disease in a rural community in India: the Indo-US study. Neurology 57: 985-989, 2001.Muthane U, Yasha TC, and Shankar SK. Low numbers and no loss of melanized nigral neurons with increasing age in normal human brains from India. Ann Neurol 43: 283-287, 1998.Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and cognitive function in the elderly. Am J Epidemiol 164(9):898-9, 2006
Epidemiological studies showed that in India, where curcumin is widely used indaily diet, there is a reduced age-adjusted prevalence of AD (in patients between70 and 79 years of age is 4.4 fold less than that of the United States), as well as alower prevalence of Parkinson’s disease.
Proc Natl Acad Sci U S A. 2007 July 31; 104(31): 12849–12854. Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcuminFiala M. et al.Department of Medicine, Greater Los Angeles Veteran's Affairs Medical Center
J Clin Psychopharmacol. 2008 Feb;28(1):110-3.Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease.Baum L. et al
Tea (Camellia sinensis)
Green Tea Black Tea30-40% Catechins
3-6% Caffeine~310 mg polyphenols per 6 ounces
3-10% Catechins2-6% Theaflavins
> 20% Thearubigens3-6% Caffeine
~340 mg polyphenolsper 6 ounces
Crushed tea leaves
Polyphenol oxidase
Oxidation,Polymerization
O
OR 2
HO
OH
OH
R 1
HO
Acidi grassi essenziali
Hanbauer I, Rivero-Covelo I, Maloku E, Baca A, Hu Q, Hibbeln JR, Davis JM. The Decrease of n-3 Fatty Acid Energy Percentage in an Equicaloric Diet Fed to B6C3Fe Mice for Three Generations Elicits Obesity. Cardiovasc Psychiatry Neurol. 2009;2009:867041.
Why are PUFAs healthy?
b-OxidationFA synthesisTriglyceride synthesis
PPAR
PPRE
Fatty acid oxidation genes
+SREBP1SP1/NF-Y
Lipogenic genes
-
VLDL-TG
Okinawa 24 – 6 -06
The Okinawa Centenarian Study is based on solid scientific evidences.
This opinion addresses the scientific substantiation of health claims in relation to variousfood(s)/food constituent(s) and protection of cells from premature ageing, antioxidant activity,antioxidant content and antioxidant properties, protection of DNA, proteins and lipids fromoxidative damage, and bioavailability of anthocyanins in black currants. The scientificsubstantiation is based on the information provided by the Member States in the consolidatedlist of Article 13 health claims and references that EFSA has received from Member States ordirectly from stakeholders.
Protection of cells from premature ageingThe target population is assumed to be the general population. The proposed wordings andclarifications provided by Member States include “lowers the ageing process”, “fightingoxidation induced ageing”, “fights against cellular ageing”, and “protects the skin from theeffects of premature ageing”. The Panel considers that the claimed effect “anti-cancer” relatesto the prevention of a human disease and does not comply with the criteria laid down inRegulation (EC) No 1924/2006.No definition has been provided of “premature (skin) ageing”,“healthy ageing”, “oxidation-induced ageing” or “cellular ageing” in relation to the antioxidantproperties of foods. The Panel considers that these claimed effects are general and non-specificand do not refer to any specific health claim as required by Regulation (EC) No 1924/2006.
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In un saggio intitolato
Riguardo lo Spiritualismo e il Materialismo (1863)
Ludwig Andreas Feuerbach scrisse:
"Der Mensch ist, was er ißt."
che tradotto in Italiano:
‘Siamo cio’ che mangiamo'.