Quale ruolo delle sostanze nutrizionali efunzionali contenute negli integratorialimentari per il paziente anziano

5

6

7

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'.