Hrana za kućne ljubimceHranidba domaćih životinjaPurina istraživanjaSponzorirani članak

Utjecaj nutricionizma na produljenje životnog vijeka i kvalitete života

PROLONGING LIFE THROUGH DIETARY INTERVENTION

Clementine Jean-Philippe, DVM, PhD
Nestle Purina European Scientific Communication Manager

nestle purina

Sažetak


Dugotrajnim istraživanjem otkriveno je da se prehranom koja sadrži dodatne antioksidanse, PUFA i prebiotike povećava dugovječnost i poboljšava zdravlje starijih mačaka. Tjelesna masa i podaci o tjelesnoj građi iz istraživanja ocjenjeni su kako bi se otkrila moguća povezanost ovih parametara sa dugovječnosti. Tjelesna masa zajedno s parametrima izmjerenim pomoću DEXA (Dual Energy X-ray Absorptiometry) značajno su povezane s preživljavanjem, što potvrđuje pretpostavku da gubitak mase predstavlja faktor rizika za smrtnost kod starih mačaka. Mačke koje su se hranile hranom s dodacima bolje su održavale tjelesnu masu i građu tijekom vremena. Prehrana može imati utjecaj na promijene vezane uz starenje, na masu i na tjelesnu građu kod starijih mačaka.

Uvod


Kod svih sisavaca starenje je povezano s nizom promjena u građi tijela, opadanjem organskih funkcija i drugim metaboličkim promjenama. Sarkopenija, gubitak mišićnog tkiva povezan sa starošću i gubitak na masi, česta je kod starijih ljudi, mačaka i drugih vrsta. Prehrana može imati važnu ulogu u odgađanju takvih promjena ili prevenciji njihovog napredovanja.

Istraživanja kod mačaka dala su nam podatke prema kojima stare odrasle mačke možemo podijeliti u dvije kategorije na osnovi metaboličkih razlika. Kod srednjedobne populacije mačaka (7-11 godina), prosječne potrebe za energijom smanjene su dok je prevalencija pretilosti povećana. Kod populacije starih mačaka (starih 12 i više godina), obratno je, tako da su prosječne potrebe za energijom povećane dok je prevalencija pretilosti smanjena u ovoj dobnoj skupini. Ograničenje ovakvog istraživanja je u tome što ono ne prati promjene kod pojedinih mačaka tijekom vremena, tako da nije poznato da li je smanjena prevalencija pretilosti zbog gubitka na težini i tjelesnoj kondiciji kod mačaka s vremenom ili uslijed promjena koje odražavaju ranu smrtnost od pretilih mačaka.

Prethodno, proveli smo istraživanje da bismo ocijenili utjecaj kontrole prehrane na životni vijek starih mačaka. Istraživanje je ispitivalo pretpostavku da dodatni antioksidansi sami ili u kombinaciji s poluzasićenim masnim kiselinama i prebiotoičkim vlaknima mogu mjerljivo pozitivno djelovati na zdravlje i dugovječnost starih mačaka. Od tri testirane vrste prehrane, dijeta koja je sadržavala kombinaciju dodatnih antioksidansa, prebiotik i mješavinu omega 3 i omega 6 masnih kiselina povećala je dugovječnost i poboljšala zdravlje starih mačaka.

Podaci iz tog istraživanja ocjenjeni su da bi se odredile promjene kod pojedinih mačaka u tjelesnoj građi, kroz vrijeme. Cilj je bio odrediti da li koja od tih promjena u tjelesnoj građi može biti povezana ili da li se može predvidjeti morbiditet ili mortalitet kod starih mačaka.

 

Materijali i metode


Podaci ocjenjeni u svrhu ovog istraživanja dobiveni su iz dugotrajnog istraživanja hranidbe koja je započeta sa 90 zdravih mačaka miješanih pasmina, dovedenih u naš Pet Care Centar za istraživanje prehrane. Zdrave mačke starosti između 7 i 17 godina odabrane su za ispitivanje. Mačke su ravnomjerno raspoređene na tri dijetetske skupine na osnovi dobi, ocjene tjelesne kondicije (na osnovi ljestvice od 1-5) i spola. Skupine mačaka su stavljene na jednu od tri režima prehrane: Dijeta 1 – Kontrola (osnovna kompletna i izbalansirana hrana za odrasle mačke); Dijeta 2 (osnovna hrana uz dodatak antioksidansa, vitamina E i beta karotena); Dijeta 3 (osnovna hrana s dodanim antioksidansima suhom cijelom cikorijom kao izvorom prebiotika i mješavinom dodatno n6 i n3 masnih kiselina). Hrana je davana po volji.

Klinička opažanja


Praćenje zdravstvenog stanja i liječenje svih mačaka provođeni su prema veterinarskim standardima za formiranu populaciju kroz cijeli pokus i veterinarskom osoblju nisu bili poznati podaci o prehrambenim skupinama. Osim fizičkih pregleda i rutinskog uzorkovanja krvi (biokemija i hematologija), mjerenja tjelesne mase i građe provođena su rendgenskom apsorpciometrijom (DEXA) kod svih mačaka na početku istraživanja i kasnije u tijeku. Unos hrane mjeren je dnevno kroz cijelo istraživanje i tjelesne mase su bilježene tjedno.

Statistička analiza


Analiza varijance korištena je za usporedbu početnih parametara u skupinama da se potvrdi da je nasumičnost bila djelotvorna u stvaraju ravnomjernosti u samom početku (T0) u 3 pokusne skupine.

Analiza preživljavanja napravljena je da se usporede tri dijete u dobi kada bi mačke ugibale prirodnom smrću (starost kod uginuća) i broj dana kada su mačke bile žive (Dani pokusa). Za starost kod uginuća, napravljena je neparametarska analiza Kaplan-Meier. Za dane u pokusu, korišten je Cox-ov proporcionalni model rizika da bi se usporedilo preživljavanje kod tri prehrambene skupine. Omjer slučajnosti je postavljen s 95% pouzdanosti. Pošto je bio velik raspon dobi kod mačaka u početku pokusa, početna dob mačaka je uzeta kao predviđena u modelu.

Analiza izmjerenih zdravstvenih parametara napravljena je longitudinalnom analizom. Longitudinalni model omogućio je za svaku životinju da se kretanje gleda kroz vrijeme i prosječne promjene ili smjer predvidi za svaku skupinu. Kada je bilo prikladno kvadratni model je uključen u longitudinalni model.

Da bi se odredilo da li je koji od mjerenih parametara povezan sa preživljavanjem, korišten je Cox-ov model proporcionalnog rizika za mjerene parametre kao promjenjive vrijednosti. Cox-ov model ocjenjuje da li je povećanje ili smanjenje parametara povezano s dužim ili kraćim preživljavanjem. Omjer rizika ukazuje koji postotak povećanja ili smanjenja rizika ugibanja je povezan s kojom mjernom jedinicom za taj parametar. Formula (1.00-Omjer Rizika) x 100, daje korelaciju s preživljavanjem.

Longitudinalni podaci dobiveni s DEXA za tjelesnu masu bez masnog tkiva (Lean body mass LBM) i masu masti u gramima je također ocjenjena retrospektivno od vremena uginuća za cijelu populaciju mačaka da se odredi kako promjene u tim vrijednostima mogu nagovještavati uginuće. Za težinu masti, korišten je model višestruke regresije, gdje je najprimjereniji za razdoblje najbliže uginuću kvadratni model. Za LBM, najprimjereniji za podatke, zaključeno je da je longitudinalni model linearne regresije.
Sva statistička računanja su napravljena pomoću SAS. Statistička signifikantnost je na vrijednosti P.

REZULTATI


Dugovječnost. Za analizu preživljavanja, 2 mačke su uklonjene iz pokusa unutar prvih 6 mjeseci zbog slabog uzimanja hrane i nisu uključene. Bilo je ukupno 88 mačaka u konačnim rezultatima, od kojih je 85 uginulo i 3 su uklonjene zbog slabog uzimanja hrane prije nego su uginule (ali nakon što su bile u pokusu duže od 6 mjeseci). Ove posljednje 3 mačke koje nisu završile pokus bile se isključene iz statističke analize.

Kako je prije napomenuto, mačke koje su hranjene Dijetom 3 živjele su signifikantno duže od mačaka hranjenih s Dijetom 1. Primjenom neparametarske analize za starost kod uginuća, mačke hranjene dijetom 3 živjele su približno 1.3 godine duže, u prosjeku od mačaka na prvoj dijeti (Tablica 1). Slika 1 pokazuje Kaplan-Meier krivulje za starost kod uginuća.

Cox-ova analiza regresija proporcionalnog rizika korištenjem početne starosti kao predviđene također je pokazala signifikantnu razliku između Dijete 1 i Dijete 3 kod dana u pokusu (Tablica 2). Omjer vjerojatnosti Dijete 1 prema Dijeti 3 bio je 0.418, što znači da je rizik uginuća za mačke na dijeti 3 samo 42% od vjerojatnosti uginuća mačaka na Dijeti 1. Nije bilo signifikantne razlike između Dijete 1 i Dijete 2 ili između Dijete 2 i Dijete 3.

Tjelesna masa


Sve tri prehrambene skupine s vremenom su gubile na masi, ali mačke hranjene Dijetom 3 gubile su manje od mačaka na Dijeti 1 i 2 (Slika 2). Cox-ov model proporcionalnog rizika za Dijetu 1 i 3 , uz pomoć tjelesne mase kao vremenski predviđene promjenjive vrijednosti, pokazalo je signifikantnu ovisnost između tjelesne mase i preživljavanja (Tablica 3). Uz pomoć omjera rizika u Tablici 3 za svaki kilogram povećane tjelesne mase bila je 88% povećana šansa preživljavanja, ili smanjena vjerojatnost uginuća.

Tjelesna građa


Paralelno sa tjelesnom masom sastav tijela je opadao signifikantno s vremenom u svim prehrambenim skupinama. Iako nije bilo statističkih razlika između Dijeta, bila je signifikantna povezanost između tjelesne građe i preživljavanja (Tablica 3). Za svaku vrijednost poboljšanja u tjelesnoj građi 88% je bila povećana šansa preživljavanja.

Grami i postotci tjelesne masti kao grami mase tijela bez masnog tkiva (LBM), gustoća minerala kostiju (BMD) i sadržaj minerala u kostima (BMC) pokazali su signifikantan pad s vremenom u svim pokusnim skupinama dok je % LBM i % kostiju porastao s vremenom. Općenito mačke držane na Dijeti 3 očitovale su manje promjena s vremenom od druge dvije dijetetske skupine u longitudinalnoj analizi ovih parametara. Bilo je tendencije za razlike između Dijete 1 i Dijete 3 s vremenom za % LMB (p).

Cox-ov proporcionalni model rizika za Dijetu 1 i 3, uz pomoć LBM (u gramima i %), masti (u gramima i %), BMD,BMC i BCS kao vremenski promjenjivih vrijednosti, pokazao je signifikantan odnos između tih parametara i preživljavanja (Tablica 3). LBM u gramima, masti u gramima i %, BMD, BMC i BCS bili su svi u pozitivnoj korelaciji s omjerom rizika preživljavanja manjim od 1, što je upućivalo da su veće vrijednosti ovih parametara povezane sa smanjenim rizikom od uginuća. Na primjer za svaki gram povećanja u LBM bila je 0.2% povećana mogućnost preživljavanja, a za svaki 1% povećane tjelesne masti bila je 12% veća šansa preživljavanja. Postotak LBM i postotak kostiju bili su u negativnoj korelaciji s preživljavanjem, s omjerom rizika većim od 1, što je upućivalo da su veće vrijednosti ovih parametara povezane sa većim rizikom od uginuća. Na primjer za svakih 1% povećanje u postotku, 12% bi se smanjila šansa preživljavanja.

Srednje predviđena količina LBM (g) i količine masti za sve mačke po mjesecima do smrti prikazane su na Slikama 5 i 6. Model Longitudinalna linearne regresije najbolje pristaje vrijednostima LBM i linija predviđanja pokazuje općenit progresivan pad u prosječnoj količini LBM kako se mačka bliži kraju života (Slika 5).

Količina masti u gramima pretvorena je u prirodne logaritme. Model višestruke regresije korišten je s kvadratnim modelom koji je najprikladniji za razdoblje neposredno pred uginuće, kako je prikazano krivuljom prosječnog predviđanja (Slika 6). Ova analiza je pokazala da mačke počinju gubiti mast otprilike 37 mjeseci prije uginuća, te da je pad prikazao povećano gubljenje masti prema kraju životnog vijeka. Sveobuhvatni longitudinalni uzorci srednjepredviđene količine LBM i masti prikazani su zajedno na Slici 7.

Rasprava


Ranija istraživanja koja su ocjenjivala populacije mačaka dala su pretpostaviti da je gubitak tjelesne mase kod starih mačaka rizični čimbenik za uginuće i zabilježeno je da izuzetno mršave stare mačke imaju znatno veći rizik od uginuća u usporedbi sa mačkama u optimalnoj tjelesnoj kondiciji. U trenutnom longitudinalnom istraživanju starih mačaka, ovo opažanje nije samo potvrđeno već su prošireni i zaključci. Prema ovim podacima stare mačke koje su gubile na težini i kondiciji (debele ili mršave) imale su signifikantno veći rizik od rane smrtnosti.

Kroz većinu dobnih skupina kod ljudi, veći index tjelesne mase (BMI) povezan je s povećanim morbiditetom i mortalitetom. Mršavost se preporučuje za smanjenje i odgađanje incidencije bolesti i produženje dugovječnosti kod mnogih vrsta, uključujući pse, održavanje tjelesne kondicije kroz doživotnu restrikciju kalorija pokazalo se produžuje životni vijek.

Međutim, ova povezanost između mršavosti i dugovječnosti nije očita kod starijih mačaka ili onih sa kroničnim bolestima. Naprotiv, nizak index tjelesne mase kod starih ljudi povezan je sa povećanim rizikom morbiditeta i mortaliteta, s najvećom smrtnosti opaženom kod vrlo pretilih ili vrlo mršavih, rezultat je krivulja „U“ oblika za povezanost između BMI i rizika smrti ili bolesti po dobnim skupinama. Najveći BMI i mršavost su povezani s produženim životnim vijekom u tim starijim dobnim skupinama. Veća količina masti je također bila povezana sa signifikantno nižim stopama smrtnosti kod ljudi pacijenata na hemodijalizi. Na osnovi ovdje prikazanih rezultata, povećana dugovječnost kod veće LBMi i masnog tkiva može biti istinita i kod starih mačaka također.

U ovom istraživanju, svi parametri mjereni s DEXA, kao i tjelesna masa i BSC, pokazali su signifikantnu povezanost s preživljavanjem. LBM (u gramima), masa masti ( %), gustoća minerala kostiju i sadržaj minerala u kostima, kao i BCS svi su u pozitivnoj korelaciji sa preživljavanjem, što daje naslutiti da su više vrijednosti ovih parametara povezane sa smanjenim rizikom od uginuća.
Negativna korelacija između % LBM i preživljavanja, i pozitivna korelacija između tjelesne masti i preživljavanja opažena u ovom istraživanju može prevariti ako se primjeni na krivu populaciju. Ove mačke imale su normalnu do mršavu tjelesnu kondiciju. Mačke s najvišim %LBM u ovom istraživanju imale su niske razine tjelesne masti i uslijed prekomjernog gubitka na težini njihov % LBM je povećan usprkos signifikantnom smanjenju ukupne količine.

Bitno smanjene apsolutne vrijednosti LBM i masnog tkiva jasnije odražavaju prave promjene koje se javljaju kod tih starijih mačaka sa čak za trećinu manje mišićnog tkiva u usporedbi s mjerenjima u mlađoj dobi. Viši postotak LBM i kosti i relativno nizak % masti prethodno je opisan u našim prijašnjim podacima ispitivanja populacije mačaka pred kraj njihovog životnog vijeka. Usporavanje ovog gubitka ili promjene u relativnim odnosima ovih tjelesnih tkiva teorijski bi moglo pomoći produžiti trajanje života.

Zanimljivo je da se tijekom longitudinalnih mjerenja LBM (u gramima) pokazao ravan linearni pad prije uginuća dok je masa masti (u gramima) ostala jednaka do približno 3 godine prije uginuća, a zatim je značajno opala pred kraj života.
Ovaj uzorak blisko slijedi onaj uočen kod tjelesne mase mačaka u našoj populaciji koje su počele u 4.godini prije uginuća i vjerojatno odražavaju početak kroničnih bolesti i utilizaciju rezervi tjelesnih tkiva tijekom bolesnih stanja.
Sarkopenija je česta kod starih ljudi, i prepoznaje se kao signifikantan doprinos nemoći i smrtnosti kod starih ljudi. Postoje mnogi uzroci za sarkopeniju uključujući starosno smanjenje hormona, nedjelotvornost sinteze proteina, povećana proliferacija citokina i oksidativni stres. Osim toga prehrambeni čimbenici mogu doprinijeti sarkopeniji. Neprikladan unos energije ili proteina može doprijeti velikom gubitku mišiće mase. Povećan unos proteina predlaže se kao metoda održavanja mišićne mase kod starijih pasa. Stari psi trebaju više proteina da bi postigli bolju pretvorbu, proces koji se pojačava sa starosti. Dostatna pretvorba proteina važna je za održavanje imunološkog statusa kod starijih pasa i svakako će imati utjecaj na morbiditet i mortalitet.

Mačke imaju velike potrebe za proteinima da bio držale svoj LBM, i prethodno smo prikazali podatke kroz populaciju koji pokazuju da tjelesna masa, LBM i masa masti sve opadaju kod mačaka starijih od 12 godina, pogotovo u posljednje 1-2 godine života. U ovom istraživanju, razlike u tjelesnoj građi i životnom vijeku razvile su se longitudinalno kod različitih načina prehrane. Proteinski i kalorijski sastav prehrane bio je sličan u sva tri tipa dijete. Uzimanje hrane, koje je u početku bilo slično, povećalo se kod onih dijeta kod kojih se gubilo najviše tjelesne težine. Opet, adekvatni proteini ili energija ne objašnjavaju gubitak mišića i masti.

Niti citokini niti markeri oksidativnog stresa nisu mjereni u ovom ispitivanju. Međutim, razine serumskog vitamina E bile su povišene do signifikantnih razina u skupini na Dijeti 3 i to je skupina koja je održala tjelesnu masu i sastav najboljima.

Postoji indikacija za istraživanje uloge vitamina E u zaštiti od oksidativnog stresa prilikom starenja. Pretpostavlja se da vitamin E može poboljšati zdravlje i kvalitetu života tijekom starenja kroz djelovanje na imunološku funkciju i upalne puteve. Autori su zabilježili da su stariji ljudi sa lošijim psihičkim i mentalnim zdravstvenim statusom imali niže koncentracije alfa tokoferola u cirkulaciji i povišene koncentracije upalnih markera. Upala se čini osnovnom karakteristikom starenja, i vitamin E se pokazao da posjeduje protuupalno djelovanje. Niske koncentracije vitamina E također su se pokazale značajno povezane s opadanjem psihičke funkcije kod starijih ljudi.

Moguće je da su sarkopenija i gubitak masti kod mačaka u ovom istraživanju povezane s oksidativnim stresom i da je dijeta koja je sadržavala veće količine vitamina E u serumu pomogla održati rezerve tjelesnih tkiva i pridonijeti dugovječnosti.

 

Zaključak

Podaci iz ovog longitudinalnog istraživanja potvrdili su opažanja iz prijašnjih ispitivanja da je gubitak na težini rizični faktor za smrtnost kod starijih mačaka. Osim toga, mačke koje su gubile tjelesnu mast, mišićje i koštanu masu imale su veći rizik od rane smrtnosti. U ovom istraživanju mjereni su svi parametri tjelesnog sastava kao i tjelesna masa i bili su signifikantno povezani s preživljavanjem. Retrospektivna longitudinalna analiza mišićja i masti indicirala je da prosječno LBM (u gramima) opada ravnomjerno kroz više godina prije uginuća dok mast (u gramima) se održava do 3 godine pred uginuće, a zatim pojačano opada.

Podaci također upućuju da prehrana može imati ulogu u odgađanju tih starosnih promjena u tjelesnoj težini i sastavu. Veća tjelesna masa i bolje održavanje mišića i masti može produžiti život povećanjem prehrambenih rezervi kod starijih mačaka. Dijeta koja sadrži antioksidanse, prebiotik i poluzasićene masne kiseline održavala je bolje tjelesnu težinu i građu kod starih mačaka u ovom dugotrajnom istraživanju i to je vjerojatno doprinjelo dugovječnosti.


Tablica 1. Starost kod uginuća (Ne-parametarski)


Dijeta

Srednja starost kod uginuća(godine)

P

1

14.72

Diet 1 : Diet 2

0.1429

2

15.09

Diet 1 : Diet 3

0.0074

3

16.00

Diet 2 : Diet 3

0.1121


Tablica 2. Dani u pokusu, Cox-ov model (predviđena početna starost)


Variabla

df

P

Omjer rizika

95% CI za omjer rizika

Dijeta 1 : Dijeta 2

1

0.3487

0.763

0.433-1.344

Dijeta 1 : Dijeta 3

1

0.0038

0.418

0.231-0.754

Dijeta 2 : Dijeta 3

1

0.2722

0.741

0.433-1.266


Tablica 3. Analiza preživljavanja s predviđenim promjenama vrijednosti, Dijeta 1 : Dijeta 3


Parametar

Omjer rizika

P

Korelacija preživljavanja

Tjelesna težina

0.364

<0.0001

64% povećano/kg

Ocjena tjelesne kondicije

0.117

<0.0001

88% povećano /BCS unit

DEXA LBM

0.998

<0.0001

0.2% povećano /gram

DEXA Mast g

0.996

<0.0001

0.4% povećano /gram

DEXA BMD

0.00002

0.0045

100% povećano /g/cm2

DEXA BMC

0.985

0.0161

1% povećano /gram

DEXA % LBM

1.118

0.0002

12% smanjeno/%

DEXA % Mast

0.876

<0.0001

12% povećano /%

DEXA % Kosti

2.35

<0.0001

135% smanjeno/%

Vitamin E

0.946

0.0357

5% povećano /mg/L


Slika 1. Starost kod uginuća


Slika 2. Predviđene vrijednosti mase tijela


Slika 3. Predviđene vrijednosti % LBM


Slika 4. Predviđene vrijednosti % masti


Slika 5. Predviđene vrijednosti LBM po mjesecima prije uginuća


Slika 6. Predviđene vrijednosti mase masti po mjesecima prije uginuća


Slika 7. Predviđene vrijednosti mase LBM i mase masti prije uginuća


Reference

1. Taylor EJ, Adams C, Neville R. Some nutritional aspects of ageing in dogs and cats. Proceedings of the Nutrition Society 1995;54:645-56.
2. Lambert CP, Evans WJ, Sullivan DH. Treatment of sarcopenia and cachexia in the elderly. In Mantovani G (ed). Cachexia and Wasting: A Modern Approach. Springer-Verlag, Milan, Italy. 2006:719-730.
3. Perez-Camargo G, Patil AR, Cupp CJ. Body composition changes in aging cats. Compend Contin Educ Pract Vet Suppl 2004;26(Suppl 2A):71.
4. Cupp CJ, Jean-Philippe C, Kerr WW, et al. Effect of nutritional interventions on longevity of senior cats. Intern J Appl Res Vet Med 2006;4(1):34-50.
5. Cupp CJ, Kerr WW, Jean-Philippe C, et al. The role of nutritional interventions in the longevity and maintenance of long-term health in aging cats. Intern J Appl Res Vet Med 2008;6(2):69-81.
6. Allison PD. Survival Analysis using the SAS System: A Practical Guide. The SAS Institute Inc.: Cary, NC; 1995.
7. Verbeke G, Molenberghs G. Linear Mixed Models for Longitudinal Data. Springer-Verlag: New York; 2000.
8. SAS: SAS/STAT User’s Guide. Version 9.1. Cary, NC: The SAS Institute Inc.; 2003.
9. Doria-Rose VP, Scarlett JM. Mortality rates and causes of death among emaciated cats. JAVMA 2000;216(3):347351.
10. Kvamme JM, Wilsgaard T, Florholmen J, Jacobsen BK. Body mass index and disease burden in elderly men and women: The Tromso Study. Eur J Epidemiol. Published on-line 20Jan2010.
11. Lee IM, Blair SN, Allison DB, et al. Epidemiologic data on the relationships of caloric intake, energy balance and weight gain over the life span with longevity and morbidity. J Gerontol 2001; 56A (Special Issue I):7-19.
12 Samaras TT, Storms LH, Elrick H. Longevity, mortality and body weight. Ageing Research Reviews 2002;1:673-691.
13. Kealy RD, Lawler DF, Ballam JM, et al. Effects of diet restriction on life span and age-related changes in dogs. JAVMA 2002;220(9):13151320.
14. Han SS, Kim KW, Kim K-I et al. Lean mass index: a better predictor of mortality than body mass index in elderly Asians. J Am Geriatr Soc 2010;58:312-317.
15. Flicker L, McCaul KA, Hankey GJ et al. Body mass index and survival in men and women aged 70 to 75. J Am Geriatr Soc 2010;58:234-241.
16. Gulsvik AK, Thelle DS, Mowe M, Wyller TB. Increased mortality in the slim elderly: a 42 years follow-up study in a general population. Eur J Epidemiol 2009;24:683-690.
17. Thinggaard M, Jacobsen R, Jeune B, et al. Is the relationship between BMI and mortality increasingly U-shaped with advancing age? A 10-year follow-up of persons aged 70-95 years. J Geront A Biol Sci Med Sci 2010 Jan 20 (Epub).
18. Kimyagarov S, Klid R, Levenkrohn S et al. Body mass index (BMI), body composition and mortality of nursing home elderly residents. Eur J Epidemiol 2009;24(11):683-90.
19. Kalantar-Zadeh K, Kuwae N, Wu DY et al. Associations of body fat and its changes over time with quality of life and prospective mortality in hemodialysis patients. Am J Clin Nutr 2006;83:202-210.
20. Perez-Camargo G. Cat nutrition: what is new in the old? Compend Contin Educ Pract Vet Suppl 2004;26(Suppl 2A):510.
21. Fugita S, Volpi E. Nutrition and sarcopenia of ageing. Nutr Res Reviews, 2004;17:69-76.
22. Laflamme DP. Nutrition for aging cats and dogs and the importance of body condition. Vet Clin Small Anim 2005;35:713-742.
23. Wannemacher RW, McCoy JR. Determination of optimal dietary protein requirements of young and old dogs. J Nutr 1966;88:66-74.
24. Williams CC, Cummins KA, Hayek MG, et al. Effects of dietary protein on whole-body protein turnover and endocrine function in young-adult and aging dogs. J Anim Sci 2001;79:3128-36.
25. Kealy RD. Factors influencing lean body mass in aging dogs. Compend Contin Educ Pract Vet 1999;21(Suppl 11K):34-7.
26. Tengerdy RP. Vitamin E, immune response, and disease resistance. Ann NY Acad Sci 1989;570:335-44.
27. De la Fuente M. Effects of antioxidants on immune system aging. Eur J Clin Nutr 2002;56(Suppl3):S5-8.
28. Capuron L, Moranis A, Combe N, et al. Vitamin E status and quality of life in the elderly: influence of inflammatory processes. Brit J Nutr 2009;102:1390-94.
29. Wu D, Meydani SN. Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention. J Leukocyte Biology 2008;84:900-14.
30. Singh U, Devaraj S, Jialal I. Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr 2005;25:151-74.
31. Bartali B, Frongillo EA, Guralnik JM, Stipanuk MH, Allore HG, Cherubini A, Bandinelli S, Ferrucci L, Gill TM: Serum micronutrient concentrations and decline in physical function among older persons. JAMA 2008;299:308-315.


PROLONGING LIFE THROUGH DIETARY INTERVENTION

 ABSTRACT

A longitudinal study found that a diet containing supplemental antioxidants, PUFAs, and a prebiotic increased longevity and improved health of senior cats. Body weight and body composition data from the study was evaluated to assess possible associations of these parameters with longevity. Body weights along with all body composition parameters measured by DEXA were significantly related to survival, confirming the hypothesis that loss of body mass is a risk factor for mortality in aging cats. Cats eating the supplemented diet better maintained body weight and body composition over time. Nutrition can play a role in delaying age-related changes in body weight and body composition in senior cats.

Introduction
In all mammals, aging is associated with changes in body composition, declining organ functions and other metabolic changes. Sarcopenia, an age-related loss of muscle and lean body mass, is common in aging humans, cats, and other species. Nutrition may play an important role in delaying such changes or preventing their progression.1,2
Cross-sectional studies in cats3 have documented that aging adult cats fall into two categories based on metabolic differences. In middle aged cat populations (7 to 11 years of age), average energy requirements are reduced while the prevalence of obesity is increased. In geriatric cat populations (ages 12 years and above), the reverse is true in that average energy requirements increase while the prevalence of obesity greatly decreases in this age group. A limitation of cross-sectional studies is that they do not follow changes in individual cats over time. Thus, it is not known if the reduced prevalence of obesity is due to loss of weight and body condition in cats with time, or if it is due to attrition reflecting early mortality in obese cats.
Previously, we conducted a study to evaluate the effect of dietary management on lifespan in aging cats.4,5 The study tested the hypothesis that supplemental antioxidants alone, or combining antioxidants with added polyunsaturated fatty acids and a prebiotic fiber could measurably benefit the health and longevity of aging cats. Among the 3 diets tested, the one containing a combination of supplemental antioxidants, a prebiotic, and a blend of omega-3 and omega-6 fatty acids increased longevity and improved health in senior cats.
Data from that longitudinal study was evaluated to determine changes within individual cats in body composition over time. The objective was to determine if any of these changes in body composition might be associated with or predict morbidity or mortality in aging cats.
Materials and Methods
The dataset evaluated for this paper was derived from a long-term feeding study initiated with 90 healthy mixed-breed cats, conducted in our Pet Care Center for nutritional studies. Healthy cats between the ages of 7 and 17 years were selected for the study. Cats were distributed equally among 3 dietary treatment groups, controlling for age, body condition score (based on 1 – 5 scale), and gender. Groups of cats were assigned to one of 3 diets: Diet 1 Control (basal diet of nutritionally complete and balanced adult cat food); Diet 2 (basal diet with added antioxidant vitamins E and β-carotene); and Diet 3 (basal diet with added antioxidants, dried whole chicory root as a source of prebiotic, and a blend of supplemental n-6 and n-3 fatty acids). The diets were fed, ad libitum, as the exclusive source of nutrition for the remaining natural lifetime of each cat. Typical nutrient comparisons were previously reported.4
Clinical Observations: Health monitoring and medical treatments of all cats were carried out according to established colony veterinary standards throughout the trial, and veterinary personnel were blinded to dietary treatment groups. In addition to physical examinations and routine blood sampling (serum biochemistry and hematology), measures of body weight and body composition by dual-energy x-ray absorptiometry (DEXA) were taken for all cats at study initiation and at regular intervals throughout the study. Food consumption was measured daily during the study, and body weights were assessed weekly.
Statistical Analysis
Analysis of variance was used to compare initial parameters across groups to confirm that randomization was effective in producing balance at baseline (t0) in the 3 study groups.5

Survival analyses were performed to compare the 3 diets for the age at which the cats died of natural causes (Age at Death) and the number of days the cats were alive (Days on Trial). For Age at Death, a Kaplan-Meier nonparametric analysis was performed.6 For Days on Trial, a Cox’s proportional hazard model was used to compare the survival rates of the 3 diets (pair-wise comparison).6 Hazard ratios along with their 95% confidence intervals were estimated. Because there was a wide range of ages of the cats at trial initiation, the initial age of the cat was used as a covariate in the model.
Analysis of measured health parameters was performed by a longitudinal analysis.7 The longitudinal model allowed for each animal’s trend to be considered over time and an average trend or slope predicted for each group. Where appropriate, a quadratic effect was included in the longitudinal model.
To determine if any of the measured parameters were related to survival, a Cox’s proportional hazard model was performed using the measured parameter as a time-varying covariate. The Cox’s model evaluates whether an increase or decrease of the parameter is associated with an increased or decreased rate of survival. The hazard ratio indicates what percent increase or decrease in “hazard of dying” is associated with each unit of measure for that parameter. Using the formula, (1.00 – Hazard Ratio) x 100, gives the correlation with survival.
Longitudinal DEXA data for lean body mass (LBM) and fat mass in grams also were evaluated retrospectively from the time of death for the entire population of cats to determine how changes in these measures might be predictive of death. For fat mass, a segmented regression model was used, where the best fit for the period closest to death was a quadratic model. For LBM, the best fit for the data was found to be a longitudinal linear regression model.
All statistical calculations were performed using SAS.8 Statistical significance is at the P < 0.05 level unless otherwise stated.
Results

Longevity. For the survival analysis, 2 cats were removed from trial within the first 6 months for poor food consumption and were not included. There were 88 total cats in the final data set – 85 that died, and 3 that were removed for poor food consumption before they died (but after they had been on trial for over 6 months). These last 3 cats that did not complete the trial were considered censored in the statistical analysis.

As previously reported, cats fed Diet 3 lived significantly longer than cats fed Diet 1.4,5 Using non-parametric analysis for Age at Death, cats fed Diet 3 lived approximately 1.3 years longer, on average, than cats on Diet 1 (Table 1). Figure 1 shows the Kaplan-Meier curves for Age at Death.

The Cox’s proportional hazard regression analysis using initial age as a covariate also showed a significant difference between Diets 1 and 3 for Days on Trial (Table 2). The hazard ratio of Diet 1 versus Diet 3 was 0.418, meaning that the hazard of dying for the cats on Diet 3 was only 42% of the hazard of dying for the cats on Diet 1. There were no significant differences between Diets 1 and 2 or between Diets 2 and 3.

Body Weight. All 3 diet groups lost weight over time, but cats fed Diet 3 lost less than cats on Diets 1 and 2 (Figure 2). The Cox’s proportional hazard model for Diets 1 and 3, using body weight (BW) as a time-varying covariate, showed a significant relationship between BW and survival (Table 3). Using the hazard ratios in Table 3, for every 1 kg increase in BW, there was a 64% increased chance of survival, or decreased “hazard of dying”.

Body Composition. Consistent with body weight, BCS decreased significantly over time for all dietary groups. Although there were no statistical differences between diets, there was a significant relationship between BCS and survival (Table 3). For every 1 point increase in BCS, there was an 88% increased chance of survival.

Both grams and % body fat, as well as grams LBM, bone mineral density (BMD), and bone mineral content (BMC) showed significant decreases over time for all dietary treatment groups while % LBM and % bone increased over time. In general, cats fed Diet 3 showed less change over time than the other diets in the longitudinal analysis of these parameters. There was a trend for differences between Diets 1 and 3 over time for % LBM (p < 0.10; Figure 3), % fat (Figure 4; p < 0.10), BMD, BMC, and % bone (p < 0.10).

The Cox’s proportional hazard model for Diets 1 and 3, using LBM (in grams and %), fat (in grams and %), BMD, BMC and BCS as time varying covariates showed significant relationships between these parameters and survival (Table 3). LBM in grams, fat in grams and %, BMD, BMC and BCS were all positively correlated with survival with hazard ratios less than 1, indicating that higher levels of these parameters are associated with a decreased hazard of dying. For example, for every 1 gram increase in LBM, there was a 0.2% increased chance of survival, and for every 1% increase in % body fat there was a 12% increased chance of survival. Percent LBM and % bone were negatively correlated with survival with hazard ratios greater than 1, indicating that higher levels of these parameters are associated with an increased hazard of dying. For example, for every 1% increase in % lean, there was a 12% decreased chance of survival.

Mean predicted LBM (gm) and fat mass are shown for all cats by months prior to death in Figures 5 and 6. A longitudinal linear regression model best fit the LBM data, and the prediction line shows a general progressive decrease in average LBM as the cat nears the end of its lifespan (Figure 5).

The fat mass in grams was transformed into natural logarithms to account for extreme observations. A segmented regression model was used, with a quadratic model best fitting the period closest to death, as shown by the predicted average line (Figure 6). This analysis estimated that cats start losing fat at around 37 months prior to death, and that the decline showed an increasing amount of fat loss towards the end of life. The overall longitudinal patterns of mean predicted LBM (gm) and fat mass are shown together in Figure 7.

Discussion

Prior cross-sectional studies evaluating populations of cats suggested that loss of body weight in aging cats was a risk factor for mortality,3 and it was reported that extremely lean old cats had a significantly higher risk of death compared with cats in optimal body condition.9 In the current study evaluating aging cats longitudinally, this observation was not only confirmed but the conclusions can now be expanded. According to this data, aging cats that lose excess body weight and body condition (fat or lean) have a significantly greater risk for earlier mortality.

Across most human age groups, a higher body mass index (BMI) is associated with increased morbidity and mortality.10,11,12 Staying lean is widely recommended to decrease and delay disease incidence and extend longevity. In many species, including dogs,13 maintaining a lean body condition through lifelong caloric restriction has been shown to increase longevity.

However, this relationship between leanness and longevity is not evident in older adults or those with chronic disease.14 Instead, a low body mass index in very old humans is associated with an increased risk of morbidity and mortality.10,15,16 With the highest mortality observed for the very obese and very thin, the result is a U-shaped curve for the relationship between BMI and risk of death or disease by age group.15,16 Higher BMI and lean mass have been associated with increased longevity in these elderly age groups.14,17,18 Higher fat mass was also associated with significantly lower mortality rates in human hemodialysis patients. ,19 Based on the results presented here, an increase in longevity from higher levels of lean and fat tissue may be true for aging cats as well.

In this study, all parameters measured by DEXA, as well as body weights and BCS, showed a significant relationship with survival. LBM (in grams), fat mass (in grams and %), bone mineral density and bone mineral content, as well as BCS were all positively correlated with survival, indicating that higher levels of these parameters were associated with a decreased risk of dying.

The negative correlation between % LBM and survival, and the positive correlation between body fat and survival observed in this study might be misleading if applied to the wrong population. These cats were in normal to lean body condition. The cats with the highest % LBM in this study had very low levels of body fat, and due to overall body weight loss, their % LBM was increased despite a significant reduction in total grams of lean. Substantially decreased absolute values of lean and fat tissue more clearly reflect the actual changes that are occurring in these elderly cats, with as much as a third less lean tissue compared to what is measured during young adulthood.25 A higher % LBM and bone relative to lower % fat mass previously has been described in our historical research colony data in cats toward the end of their lifespans.3 Slowing down this loss or change in relative amounts of these body tissues could theoretically help extend life expectancy.

It is interesting that the overall longitudinal data on LBM (in grams) showed a steady linear decline prior to death while fat mass (in grams) remained constant until approximately 3 years prior to death, then increasingly declined towards the end of life. This pattern closely follows that seen in body weights of our colony cats that were tracked in the 4 years preceding their death20 and likely reflects the onset of chronic disease and more rapid utilization of body tissue reserves during disease states.

Sarcopenia is common in aging humans, and is recognized as a significant contributor to disability and mortality in geriatric people.2,21 There are many causes of sarcopenia, including age-related decreases in hormones, inefficiencies in protein synthesis, increased proinflammatory cytokines and oxidative stress.2,21 In addition, dietary factors can contribute to sarcopenia. Inadequate intake of energy or protein can contribute to gradual loss of lean body mass.2

Increased dietary protein has been proposed as a means of preserving LBM in older dogs.22 Old dogs require more protein to achieve better protein turnover, a process which decreases with increasing age.23,24 Sufficient protein turnover is important for preserving immune competence in the older dog and will certainly have an effect on morbidity and mortality.22,25

Cats have high protein requirements to maintain their LBM, and we previously reported cross-sectional population data showing that body weight, LBM, and fat mass all decline in cats over the age of 12 years, particularly in the last 1 to 2 years of life.3,20 In this study, where differences in body composition and lifespan developed longitudinally among different dietary treatments, protein and caloric density of the diets was similar across all 3 diets. Food consumption, while initially similar, increased in those diet groups that lost the most body weight.4 Hence, inadequate protein or calories does not explain the loss of lean and fat mass.

Neither inflammatory cytokines nor markers of oxidative stress were measured in this study. However, serum vitamin E levels were increased to a significantly greater extent in the Diet 3 cats,5 and this is the group that maintained body weight and body composition to a greater extent.

There is a considerable body of research on the role vitamin E plays in protecting against oxidative stress in aging.26,27 It has been hypothesized that vitamin E status may alter health and quality of life during aging through effects on immune function and inflammatory pathways.28 These authors reported that elderly humans with poorer physical and mental health status had lower circulating concentrations of alpha-tocopherol and increased concentrations of inflammatory markers. Inflammation does appear to be a fundamental characteristic of aging, and vitamin E has been shown to exert anti-inflammatory actions.29,30 Low concentration of vitamin E also was found to be significantly associated with decline in physical function in elderly adults.31

It is possible that the sarcopenia and fat loss in the cats on this study was related to oxidative stress, and that the diet that maintained higher serum vitamin E levels helped maintain body tissue reserves and contributed to an overall increase in longevity.

CONCLUSIONS
Data from this longitudinal study confirm observations from previous cross-sectional studies that weight loss is a risk factor for mortality in aging cats. Additionally, cats that lose body fat, lean and bone mass are at greater risk for earlier mortality. In this study, all body composition parameters measured as well as body weight were significantly related to survival. A retrospective longitudinal analysis of lean and fat mass indicated that, on average, LBM (in grams) declines at a steady rate for many years prior to death, while fat mass (in grams) is maintained until around 3 years before death, then increasingly declines.

The data also suggests that nutrition can play a role in delaying these age-related changes in body weight and body composition. Higher body weights and better maintenance of lean and fat mass may extend life by providing increased nutritional reserves in these elderly cats. The diet containing supplemental antioxidants, a prebiotic and polyunsaturated fatty acids better maintained body weight and body composition in the senior cats on this long term study, and this likely contributed significantly to their increased longevity.

Table 1. Age at Death (Non-Parametric)

Diet

Mean Age at Death (Years)

P Value

1

14.72

Diet 1 vs Diet 2

0.1429

2

15.09

Diet 1 vs Diet 3

0.0074

3

16.00

Diet 2 vs Diet 3

0.1121

 

Table 2. Days on Trial, Cox Regression (Initial Age as Covariate)

Variabe

df

P Value

Hazard Ratio

95% CI for Hazard Ratio

Diet 1 vs Diet 2

1

0.3487

0.763

0.433-1.344

Diet 1 vs Diet 3

1

0.0038

0.418

0.231-0.754

Diet 2 vs Diet 3

1

0.2722

0.741

0.433-1.266

 

 

Table 3. Survival Analysis with Time-Varying Covariate, Diet 1 vs Diet 3

Parameter

Hazard Ratio

P Value

Survival Correlation

Body Weight

0.364

<0.0001

64% increase/kg

Body Condition Score

0.117

<0.0001

88% increase/BCS unit

DEXA Lean g

0.998

<0.0001

0.2% increase/gram

DEXA Fat g

0.996

<0.0001

0.4% increase/gram

DEXA BMD

0.00002

0.0045

100% increase/g/cm2

DEXA BMC

0.985

0.0161

1% increase/gram

DEXA % Lean

1.118

0.0002

12% decrease/%

DEXA % Fat

0.876

<0.0001

12% increase/%

DEXA % Bone

2.35

<0.0001

135% decrease/%

Vitamin E

0.946

0.0357

5% increase/mg/L

 

Figure 1. Age at Death

Figure 2.Body Weight Predicted Means

Figure 3.% LBM Predicted Means

Figure 4.% Fat Predicted Means

Figure 5. Mean Predicted LBM by Months Prior to Death

Figure 6. Mean Predicted Fat Mass by Months Prior to Death

Figure 7. Mean Predicted LBM and Fat Mass Prior to Death

 

References

1 Taylor EJ, Adams C, Neville R. Some nutritional aspects of ageing in dogs and cats. Proceedings of the Nutrition Society 1995;54:645-56.
2. Lambert CP, Evans WJ, Sullivan DH. Treatment of sarcopenia and cachexia in the elderly. In Mantovani G (ed). Cachexia and Wasting: A Modern Approach. Springer-Verlag, Milan, Italy. 2006:719-730.
3. Perez-Camargo G, Patil AR, Cupp CJ. Body composition changes in aging cats. Compend Contin Educ Pract Vet Suppl 2004;26(Suppl 2A):71.
4. Cupp CJ, Jean-Philippe C, Kerr WW, et al. Effect of nutritional interventions on longevity of senior cats. Intern J Appl Res Vet Med 2006;4(1):34-50.
5. Cupp CJ, Kerr WW, Jean-Philippe C, et al. The role of nutritional interventions in the longevity and maintenance of long-term health in aging cats. Intern J Appl Res Vet Med 2008;6(2):69-81.
6. Allison PD. Survival Analysis using the SAS System: A Practical Guide. The SAS Institute Inc.: Cary, NC; 1995.
7. Verbeke G, Molenberghs G. Linear Mixed Models for Longitudinal Data. Springer-Verlag: New York; 2000.
8. SAS: SAS/STAT User’s Guide. Version 9.1. Cary, NC: The SAS Institute Inc.; 2003.
9. Doria-Rose VP, Scarlett JM. Mortality rates and causes of death among emaciated cats. JAVMA 2000;216(3):347351.
10. Kvamme JM, Wilsgaard T, Florholmen J, Jacobsen BK. Body mass index and disease burden in elderly men and women: The Tromso Study. Eur J Epidemiol. Published on-line 20Jan2010.
11. Lee IM, Blair SN, Allison DB, et al. Epidemiologic data on the relationships of caloric intake, energy balance and weight gain over the life span with longevity and morbidity. J Gerontol 2001; 56A (Special Issue I):7-19.
12 Samaras TT, Storms LH, Elrick H. Longevity, mortality and body weight. Ageing Research Reviews 2002;1:673-691.
13. Kealy RD, Lawler DF, Ballam JM, et al. Effects of diet restriction on life span and age-related changes in dogs. JAVMA 2002;220(9):13151320.
14. Han SS, Kim KW, Kim K-I et al. Lean mass index: a better predictor of mortality than body mass index in elderly Asians. J Am Geriatr Soc 2010;58:312-317.
15. Flicker L, McCaul KA, Hankey GJ et al. Body mass index and survival in men and women aged 70 to 75. J Am Geriatr Soc 2010;58:234-241.
16. Gulsvik AK, Thelle DS, Mowe M, Wyller TB. Increased mortality in the slim elderly: a 42 years follow-up study in a general population. Eur J Epidemiol 2009;24:683-690.
17. Thinggaard M, Jacobsen R, Jeune B, et al. Is the relationship between BMI and mortality increasingly U-shaped with advancing age? A 10-year follow-up of persons aged 70-95 years. J Geront A Biol Sci Med Sci 2010 Jan 20 (Epub).
18. Kimyagarov S, Klid R, Levenkrohn S et al. Body mass index (BMI), body composition and mortality of nursing home elderly residents. Eur J Epidemiol 2009;24(11):683-90.
19. Kalantar-Zadeh K, Kuwae N, Wu DY et al. Associations of body fat and its changes over time with quality of life and prospective mortality in hemodialysis patients. Am J Clin Nutr 2006;83:202-210.
20. Perez-Camargo G. Cat nutrition: what is new in the old? Compend Contin Educ Pract Vet Suppl 2004;26(Suppl 2A):510.
21. Fugita S, Volpi E. Nutrition and sarcopenia of ageing. Nutr Res Reviews, 2004;17:69-76.
22. Laflamme DP. Nutrition for aging cats and dogs and the importance of body condition. Vet Clin Small Anim 2005;35:713-742.
23. Wannemacher RW, McCoy JR. Determination of optimal dietary protein requirements of young and old dogs. J Nutr 1966;88:66-74.
24. Williams CC, Cummins KA, Hayek MG, et al. Effects of dietary protein on whole-body protein turnover and endocrine function in young-adult and aging dogs. J Anim Sci 2001;79:3128-36.
25. Kealy RD. Factors influencing lean body mass in aging dogs. Compend Contin Educ Pract Vet 1999;21(Suppl 11K):34-7.
26. Tengerdy RP. Vitamin E, immune response, and disease resistance. Ann NY Acad Sci 1989;570:335-44.
27. De la Fuente M. Effects of antioxidants on immune system aging. Eur J Clin Nutr 2002;56(Suppl3):S5-8.
28. Capuron L, Moranis A, Combe N, et al. Vitamin E status and quality of life in the elderly: influence of inflammatory processes. Brit J Nutr 2009;102:1390-94.
29. Wu D, Meydani SN. Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention. J Leukocyte Biology 2008;84:900-14.
30. Singh U, Devaraj S, Jialal I. Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr 2005;25:151-74.
31. Bartali B, Frongillo EA, Guralnik JM, Stipanuk MH, Allore HG, Cherubini A, Bandinelli S, Ferrucci L, Gill TM: Serum micronutrient concentrations and decline in physical function among older persons. JAMA 2008;299:308-315.

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