Prof. dr. sc.Prof. dr. sc. Ivica RubeljIvica Rubelj

Laboratorij za molekularnu i staničnu biologijuLaboratorij za molekularnu i staničnu biologiju

Zavod za molekularnu Zavod za molekularnu biologiju, biologiju, IRBIRB

MEHANIZMI STARENJA MEHANIZMI STARENJA

I DUGOVJEČNOSTII DUGOVJEČNOSTI

Skeptici 2013

Starenje je Starenje je procesproces sveobuhvatnog sveobuhvatnog, , ireverireverzzibibiillnog inog i progresiv progresivnognog tjelesnog tjelesnog propadanja koje se događa tijekom propadanja koje se događa tijekom vremenavremena..

Genes, Aging, and Immortality. Charlotte A. SpencerGenes, Aging, and Immortality. Charlotte A. Spencer

Što je starenjeŠto je starenje??

StarenjeStarenje ??

Alchemist searching for the Philosopher's Stone Joseph Wright of Derby

Eduard Veith - Fountain of Youth

Na dugovječnost se može utjecati !Na dugovječnost se može utjecati !

Porast broja stogodišnjaka u SADPorast broja stogodišnjaka u SAD

Jeanne Louise Calment:21 February 1875 – 4 August 1997

Starenje se odvija na staničnoj razini !Starenje se odvija na staničnoj razini !

Starenje kontroliraju telomere!Starenje kontroliraju telomere!

L. Hayflick

Stanično starenjeStanično starenje

HL

mladi fibroblasti stari fibroblasti

In vitroIn vitro

35 god.

75 god.

In vivoIn vivo

Accumulation of senescent cells in tissues

TELOMERE ?TELOMERE ?

TelomereTelomere

??

Telomere ↔ stanično starenje ?

Teorija marginotomije

mlade

stare

TelomerazaTelomeraza

C. Greider

TelomerazaTelomeraza

spolne stanicespolne stanice

matične stanice matične stanice

tumorske stanicetumorske stanice

jednostaničnicijednostaničnici

J. Shay W. Wright

Telomeraza u normalnim fibroblastimaTelomeraza u normalnim fibroblastima

HL

HL

Mice overexpressing telomerase (TERT) age more slowly than normal mice. (Blasco laboratory)

Ekspresija telomeraze na razini organizmaEkspresija telomeraze na razini organizma

Maria A. Blasco

Tert delays ageing. Survival curves and % mice living for more than three years. Neuromuscular coordination as % of mice passing the tightrope test.

Tomas-Loba et al. Cell 135, 609–622, November 14, 2008

Or Not….Or Not….

TWO MICE INVOLVED IN AN EXPERIMENT ON AGE-RELATED DEGENERATION. MICE WHOSE TELOMERASE GENE WAS ACTIVATED SHOWED NOTABLE IMPROVEMENTS

Ronald A. DePinho

Reeksprimiranje telomereze na razini organizma

Telomere kao indikatori dugovječnosti, Telomere kao indikatori dugovječnosti, bolesti, stresa...bolesti, stresa...

Adapted from: Tsuji, A., A. Ishiko, et al. (2002). "Estimating age of humans based on telomere shortening." Forensic Sci Int 126(3): 197-9.

Zašto mjeriti telomere?Zašto mjeriti telomere?

Association of telomere length in blood DNA after age 60 with subsequent survival.Data are plotted as fitted and smoothed survival curves, according to the group prognosis method. Longer identifies individuals from the top half of the telomere length distribution and shorter those from the bottom half of the distribution. Years since draw means the interval ending with that year (eg, 71 people at risk at end of year 1 for longer group, both sexes).

Predikcija dugovječnosti?

The relationship between telomere length and survival in humans (after Bakaysa et al. 2007). Those with the longest telomere lengths have the highest survival prospects.

Telomere length (adjusted for age, gender, and group) according to the absence (gray bars) or presence (white bars) of various age-related diseases in the study subjects. Number of individuals analyzed in each group: hypertension (n = 125), without hypertension (n = 142), with the metabolic syndrome (n = 59), without the metabolic syndrome (n = 286), diabetes (n = 34), without diabetes (n = 276). The MMSE (Mini-Mental State Examination) was performed in centenarians only: MMSE score ≤25 (gray bars, n = 46) or >25 (white bars, n = 32). *P < 0.05.

Dulje telomere – bolje zdravljeDulje telomere – bolje zdravlje

Telomere Length in the Newborn

Žene žive duže

Telomere length and telomerase activity levels in extreme high- and low-stress groups.(A) Average telomere length and SE are shown. The highstress group had shorter

telomeres even after controlling for age.(B) Average telomerase activity and SE are shown. The high-stress group had lower

telomerase activity even after controlling for age.

STRESSTRES

!!

Može li se utjecati na naše Može li se utjecati na naše

telomere i starenje?telomere i starenje?

Longer lives: In tests, the anti-ageing pill increased the life expectancy of animals by 38 per cent

Starenje i prehranaStarenje i prehrana

Resveratrol

(Reprinted) JAMA, January 20, 2010—Vol 303, No. 3

Zdraviji metabolizam – sporiji gubitak telomera

ANALITIKA ANALITIKA TELOMERATELOMERA

Laboratorij za molekularnu i staničnu biologiju, IRB

Elizabeth BlackburnElizabeth Blackburn

Odlučite živjeti duže i zdravije!Odlučite živjeti duže i zdravije!

Sports & recreationSports & recreationAnti-aging foodAnti-aging food

ZAHVALJUJEM NA POZORNOSTIZAHVALJUJEM NA POZORNOSTI