Shiela Stefani

1
 Masa Muda vs Masa Tua
Cegah
Kompensasi
gangguan Sebagian
dan
Masa muda fenotipik dan besar bebas
homeostatik
penurunan dari penyakit
yang efektif
fungsi

Kompensasi Akumulasi
dan kerusakan Penurunan
Lansia
homeostatik tidak dapat fungsi
tidak efektif diperbaiki

Ferrucci L, Gonzalez‐Freire M, Fabbri E, Simonsick E, Tanaka T, Moore Z, et al. Measuring biological aging in humans: A quest. Aging Cell.
2020;19(2):e13080. 2
 Prevalensi Lansia
Menurut WHO, 2020,
Lansia di kawasan Asia
Tenggara sebesar 8%
atau sekitar 142 juta jiwa

http://p2ptm.kemkes.go.id/kegiatan-p2ptm/aceh/populasi-lansia-diperkirakan-terus-meningkat-hingga-tahun-
2020#:~:text=Pada%20tahun%202000%20jumlah%20Lansia,34%25)%20dari%20total%20populasi. 3
Usia harapan hidup (UHH) menjadi salah 1 indikator
keberhasilan pembangunan bidang kesehatan
Pusat Data dan Informasi Kementerian Kesehatan RI. Situasi dan Analisis Lanjut Usia.
https://pusdatin.kemkes.go.id/download.php?file=download/pusdatin/infodatin/infodatin-lansia.pdf 4
 Proses Penuaan
Proses penuaan berhubungan dengan
genetik dan lingkungan.
Penuaan normal (a) dan jalur yang
mempercepat penuaan (b dan c).
Percepatan penuaan→ akumulasi
kerusakan (b) atau ↓ mekanisme
pertahanan (c).
Seseorang dalam kondisi baik, bisa telah
terjadi kerusakan tinggi (b) atau
mekanisme pertahanan rendah (c)

Ferrucci L, Gonzalez‐Freire M, Fabbri E, Simonsick E, Tanaka T, Moore Z, et al. Measuring biological aging in humans: A quest. Aging Cell.
2020;19(2):e13080.
Park JH, Yoo Y, Park YJ. Epigenetics: linking nutrition to molecular mechanisms in aging. Preventive nutrition and food science. 2017;22(2):81 5
Faktor yang Memengaruhi
Penuaan

Evangelakou Z, Manola M, Gumeni S, Trougakos IP. Nutrigenomics as a tool to

study the impact of diet on aging and age-related diseases: the Drosophila
approach. Genes & nutrition. 2019;14(1):1-18
6
Vidaček NŠ, Nanić L, Ravlić S, Sopta M, Gerić M, Gajski G, et al.
Telomeres, nutrition, and longevity: can we really navigate our aging?
The Journals of Gerontology: Series A. 2018;73(1):39-47 10
 Karbohidrat – Panjang Telomer

Systematic review, 2016

Asupan serat Sereal dan roti

Asupan sereal 5 hasil
rendah → putih berbanding
> median → lainnya tidak
telomer quintil terbalik panjang
telomer pendek signifikan
terendah telomer
(n=1743)
(n=2284) (n=287)

Rafie N, Hamedani SG, Barak F, Safavi S, Miraghajani M. Dietary patterns, food groups and telomere length: a systematic review of current
studies. European journal of clinical nutrition. 2017;71(2):151-8
11
 Karbohidrat Sederhana

Tepung telah
melalui proses
pengilangan
komponen bran
(sekam) dan
germ→
mengurangi serat
dan fitokimia
Evangelakou Z, Manola M, Gumeni S, Trougakos IP. Nutrigenomics as a tool to study the impact of diet on aging and age-related diseases:
the Drosophila approach. Genes & nutrition. 2019;14(1):1-18
12
 Gula

Lee, dkk (cohort 10 tahun, >1900 subjek)&Leung, dkk (5309 subjek dewasa)
Konsumsi minuman manis berkarbonasi→ telomer lebih pendek

Gula tambahan→ beban glikemik → resistensi insulin, inflamasi, dan stress

oksidatif

Gula meningkatkan degradasi protein (kolagen dan elastin)→ premature

wrinkle

Lee JY, Jun NR, Yoon D, Shin C, Baik I. Association between dietary patterns in the remote past and telomere length. Eur J Clin Nutr 2015; 69: 1048–1052
Leung CW, Laraia BA, Needham BL, Rehkopf DH, Adler NE, Lin J et al. Soda and cell aging: associations between sugar-sweetened beverage consumption and
leukocyte telomere length in healthy adults from the National Health and Nutrition Examination Surveys. Am J Public Health 2014; 104: 2425–2431.
Rafie N, Hamedani SG, Barak F, Safavi S, Miraghajani M. Dietary patterns, food groups and telomere length: a systematic review of current studies. European journal of
clinical nutrition. 2017;71(2):151-8
13
 CNS, central nervous system; GI, glycemic
index; GIP, glucose-induced insulinotropic
peptide; mTOR, mammalian target of
rapamycin; NPY, neuropeptide Y.

Pfeiffer AF, Keyhani-Nejad F. High glycemic index metabolic damage–a

pivotal role of GIP and GLP-1. Trends in Endocrinology & Metabolism.
2018;29(5):289-99.
14
 GI dan GL

Carneiro L, Leloup C. Mens sana in corpore sano: Does the Glycemic Index
Have a Role to Play? Nutrients. 2020;12(10):2989 15
16
Rekomendasi Asupan Karbohidrat Sederhana

<10% kalori total harian

Contoh:
Kebutuhan kalori harian 2000kkal
2000kkal * 10% = 200kkal
1gram karbohidrat = 4 kkal
200/4 = 50 gram/hari

17
 Processed Meat

Mengandung tinggi AGEs→ menginduksi

mediator inflamasi dan meningkatkan stress
oksidatif

Rafie N, Hamedani SG, Barak F, Safavi S, Miraghajani M. Dietary patterns, food groups and telomere length: a systematic review of current
studies. European journal of clinical nutrition. 2017;71(2):151-8

18
Roorda MM. Therapeutic interventions against
accumulation of advanced glycation end products
(AGEs). Glycative Stress Res. 2017;4(2):132-43

19
Roorda MM. Therapeutic interventions against
accumulation of advanced glycation end products
(AGEs). Glycative Stress Res. 2017;4(2):132-43

20
 Karbohidrat Sederhana dan Lemak Jenuh

Low-grade
inflammation
Inflamasi lokal (inflammaging)
dan sistemik
Menghasilkan
produk yang
Disbiosis merugikan
mikrobiota kesehatan
Karbohidrat usus
sederhana

Grosso G. Nutrition and aging: is there a link to cognitive health? : Taylor & Francis; 2020 21
c-Jun aminoterminal kinase (JNK)

Devaraj S, Hemarajata P, Versalovic J. The

human gut microbiome and body
metabolism: implications for obesity and
diabetes. Clinical chemistry.
2013;59(4):617-28

23
 Daging Merah – Panjang Telomer

1958 Daging merah Konsumsi

Telomer yang
dewasa dan & processed tinggi
lebih panjang
lansia Korea meat rendah legumes

840 dewasa Konsumsi

Berhubungan terbalik dengan
processed
multietnik panjang telomer
meat

Lee JY, Jun NR, Yoon D, Shin C, Baik I. Association between dietary patterns in the remote past and telomere length. Eur J Clin
Nutr 2015; 69: 1048–1052. 21 Nettleton JA, Diez-Roux A, Jenny NS, Fitzpatrick AL, Jacobs DR Jr. Dietary patterns, food
groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 2008; 88: 1405–1412.
Rafie N, Hamedani SG, Barak F, Safavi S, Miraghajani M. Dietary patterns, food groups and telomere length: a systematic review of current
studies. European journal of clinical nutrition. 2017;71(2):151-8
24
 Cross sec
laki2 Finlandia Lemak
>57th (N:1942)
Cross sec post-
Asupan Asupan menopausal
lemak total asam lemak perempuan
dan SFA jenuh Amerika (N:4029)

Asupan Asupan Cross sec

lemak total PUFA >43th
dan cooking terutama (N: 2284)
oils Telomer C18:2n-6
Cross sec lebih
pada Wanita pendek
usia lanjut
Bias studi, hasil kontroversial
etnis Cina Tidak membedakan efek n-6 dan n-3 PUFA
(N:608)
Freitas-Simoes T-M, Ros E, Sala-Vila A. Nutrients, foods, dietary patterns and telomere length: Update of epidemiological studies and randomized trials.
Metabolism. 2016;65(4):406-15 25
 Lemak – Panjang
Telomer

Studi perempuan post-

menopause
(n = 4029)
Semakin tinggi asupan
SFA→ telomer lebih
pendek

Song Y, You NC, Song Y, Kang MK, Hou L, Wallace R, et al. Intake of small-to-medium-chain saturated fatty acids is associated with peripheral leukocyte
telomere length in postmenopausal women. J Nutr 2013;143(6):907–14.
26
 COX, cyclooxygenase; CYP, cytochrome
P450; EET, epoxyeicosatrienoic acid;
ELOVL, elongase; LOX, lipoxygenase;
LT, leukotriene; PG, prostaglandin;
TXA, thromboxane.

Balić A, Vlašić D, Žužul K, Marinović B, Bukvić Mokos Z. Omega-3 versus omega-6 polyunsaturated fatty acids in the prevention and treatment of inflammatory skin diseases. International journal of molecular
sciences. 2020;21(3):741 27
 Rekomendasi Asupan Lemak

SFA <10%; AHA <7%

ALA
0,5-2%
Lemak total 25-35% LA
PUFA 6-11%
kalori total 2,5-9%

EPA+DHA
250 mg/hari
MUFA

Harika RK, Eilander A, Alssema M, Osendarp SJ, Zock PL. Intake of fatty acids in general populations worldwide does not meet dietary recommendations to prevent coronary heart disease: a
systematic review of data from 40 countries. Annals of Nutrition and Metabolism. 2013;63(3):229-38.
Ooi EMM, Lichtenstein AH, Millar JS, Diffenderfer MR, Lamon-Fava S, dkk. Effect of Therapeutic Lifestyle Change diets high and low in dietary fish-derived FAs on lipoprotein metabolism in
middle-aged and elderly subjects. J Lipid Res 2012;53:1958-67
Johnson R, Appel L, Brands M, et al. Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. Circulation 2009;120:1011-20
28
 Produk Susu – Panjang Telomer

4029 post-menopause sehat

➢ Konsumsi susu non skim →
1958 dewasa dan lansia Korea telomer lebih pendek dibanding
konsumsi susu skim
➢ Semakin tinggi asupan produk
➢ Asupan keju mengandung
susu→ telomer semakin
lemak→ telomer lebih pendek
panjang (tidak membedakan
dibandingkan konsumsi keju
susu rendah/tinggi lemak)
low/non fat

Song Y, You NC, Song Y, Kang MK, Hou L, Wallace R et al. Intake of small-tomedium-chain saturated fatty acids is associated with
peripheral leukocyte telomere length in postmenopausal women. J Nutr 2013; 143: 907–914.
Rafie N, Hamedani SG, Barak F, Safavi S, Miraghajani M. Dietary patterns, food groups and telomere length: a systematic review of current
studies. European journal of clinical nutrition. 2017;71(2):151-8 29
Makanan Sumber
Lemak

Sun L, Zong G, Li H, Lin X. Fatty acids and

cardiometabolic health: a review of studies in
Chinese populations. European Journal of
Clinical Nutrition. 2021;75(2):253-66

30
 Alkohol

Endotoksemia

Konsumsi alkohol Perubahan komposisi

mikrobiota usus

Inflamasi

Penurunan jumlah Bacteroidaceae dari filum Bacteroidetes

Mutlu EA, Gillevet PM, Rangwala H, Sikaroodi M, Naqvi A, Engen PA, dkk. Colonic microbiome is altered in alcoholism. Am J
Physiol Gastrointest Liver Physiol 2012;302(9):966-78.
32
 Alkohol - Aging

Case Control Penelitian Lain

Kesimpulan
457 laki Italia Konsumsi moderate
Masih perlu penelitian
pemendekan telomer alcohol → efek
apakah efek tersebut
~ peningkatan kesehatan (protektif
disebabkan karena
konsumsi alkohol terhadap penyakit
kandungan etanol,
(drink-units/day) → kardiovaskular,
atau bioaktif lain atau
alcohol abusers > kognitif, fungsi fisik,
efek interaksinya
social drinkers dan mortalitas

Freitas-Simoes T-M, Ros E, Sala-Vila A. Nutrients, foods, dietary patterns and telomere length: Update of epidemiological studies and randomized trials. Metabolism. 2016;65(4):406-15.
Strandberg TE, Strandberg AY, Saijonmaa O, Tilvis RS, Pitkälä KH, Fyhrquist F. Association between alcohol consumption in healthy midlife and telomere length in older
men. The Helsinki Businessmen Study. Eur J Epidemiol 2012;27(10): 815–22
33
 Alkohol - Aging

Studi jangka panjang (3 dekade)→ efek negatif serta

pemendekan telomer bahkan pada konsumsi alkohol yang sedikit

Perbedaan panjang telomer antara kelompok dengan dan tanpa

mengonsumsi alkohol ~ perbedaan 10 tahun usia biologis

Studi Copenhagen City Heart → konsumsi alkohol ≠ panjang

telomer yang diukur setelah 10 tahun.

Freitas-Simoes TM, Ros E, Sala-Vila A. Nutrients, foods, dietary patterns and telomere length: update of epidemiological studies and
randomized trials. Metabolism. 2016;65:406–415. doi:10.1016/j.metabol.2015.11.004.
Vidaček NŠ, Nanić L, Ravlić S, Sopta M, Gerić M, Gajski G, et al. Telomeres, nutrition, and longevity: can we really navigate our aging? The Journals of
Gerontology: Series A. 2018;73(1):39-47 34
 Alkohol - Aging
Helsinki Businessmen Study (n = 499)
• Peningkatan konsumsi alkohol pada usia paruh baya (>55 tahun)→ telomer lebih
pendek di usia tua (mean 76 tahun)

Perempuan Amerika post-menopause (n = 4029)

• Peningkatan asupan alkohol→ penurunan panjang telomer

Prospektif kohort, 10 tahun (n = 4576)

• Tidak ada hubungan konsumsi alkohol dengan panjang telomer

Penelitian di tikus
• Red wine moderate (setara 0,15mg% resveratrol)→ mempertahankan panjang
telomer sel aorta dibandingkan kontrol

Strandberg TE, Strandberg AY, Saijonmaa O, Tilvis RS, Pitkälä KH, Fyhrquist F. Association between alcohol consumption in healthy midlife and telomere length in older men. The Helsinki Businessmen Study. Eur J Epidemiol 2012;27(10): 815–22.
Song Y, You NC, Song Y, Kang MK, Hou L, Wallace R, et al. Intake of small-to-medium-chain saturated fatty acids is associated with peripheral leukocyte telomere length in postmenopausal women. J Nutr 2013;143(6):907–14.
Weischer M, Bojesen SE, Nordestgaard BG. Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart. PLoS Genet 2014;10(3): e1004191.
da Luz PL, Tanaka L, Brum PC, Dourado PM, Favarato D, Krieger JE, et al. Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats. Atherosclerosis 2012;224(1):136–42.
Freitas-Simoes T-M, Ros E, Sala-Vila A. Nutrients, foods, dietary patterns and telomere length: Update of epidemiological studies and randomized trials. Metabolism. 2016;65(4):406-15
35
 Efek
Konsumsi
Etanol

van de Loo AJ, Mackus M, Kwon O, Krishnakumar IM, Garssen J, Kraneveld AD, et al. The inflammatory response to alcohol consumption
and its role in the pathology of alcohol hangover. Journal of Clinical Medicine. 2020;9(7):2081.
37
 Metabolisme Etanol

Aldehyde
dehydrogenase berperan
dalam metabolism
etanol

Allel A pada gen ALDH

rs671→ slower alcohol
metabolism

van de Loo AJ, Mackus M, Kwon O, Krishnakumar IM, Garssen J, Kraneveld AD, et al. The inflammatory response to alcohol consumption
and its role in the pathology of alcohol hangover. Journal of Clinical Medicine. 2020;9(7):2081.
Cho Y, et al. Scientific Reports 8. 2018. 458.
38
 Pemberian alkohol secara akut (moderate)→ inhibisi aktivasi
NF-kB dan TNF-α yang diinduksi oleh LPS pada tikus.
Szabo G. Moderate drinking, inflammation, and liver disease. Annals of epidemiology. 2007;17(5):S49-S54 39
Curtis BJ, Zahs A, Kovacs EJ. Epigenetic targets for reversing immune defects caused by alcohol exposure. Alcohol research: current
reviews. 2013;35(1):97
40
 Curtis BJ, Zahs A, Kovacs EJ. Epigenetic targets for reversing immune
defects caused by alcohol exposure. Alcohol research: current reviews.
2013;35(1):97

Chronic alcohol consumption skews macrophage polarization toward an M1 (i.e., pro-inflammatory)

phenotype. microRNA 155 (miR-155) and histone deacetylase inhibitors—can potentionally reverse protein
translation or gene transcription of M1 pro-inflammatory cytokines. histone lysine (H3K27) demethylases—
increase transcription of M2 anti-inflammatory cytokines. 41
 Batas Asupan Alkohol

Alkohol (14 gram/hari untuk wanita, 28 gram/hari untuk laki-laki)

Contoh yang setara dengan satu ekivalen minuman beralkohol

(14 gram alkohol murni):

12 ons (360 mL) bir 5 ons (150 mL) wine 1,5 ons (45 mL) spirits
(alkohol 5%) (alkohol 12%) (alkohol 40%).

U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. Edisi ke-8.
2015. http://health.gov/dietaryguidelines/2015/guidelines/
42
 Obesitas - Aging

Mundstock, dkk. systematic review dan meta analysis

Obesitas:
Efek obesitas
terhadap Hyperplasia dan Alasan terjadi obesitas
Peningkatan produksi
panjang hipertrofi adiposit→ sentral belum diketahui
adipokin dan stres
telomer (63 hipoksia adiposit→ dengan jelas, namun
oksidatif yang
study, 119.439 peningkatan produksi diperkirakan terkait
berhubungan dengan tingginya ROS dan
subjek) adipokin→ peningkatan
obesitas sentral rendahnya antioksidan
pro-inflamasi

Mundstock E, Sarria EE, Zatti H, Mattos Louzada F, Kich Grun L, Herbert Jones M, et al. Effect of obesity on telomere length: systematic review and
meta‐analysis. Obesity. 2015;23(11):2165-74.
43
 Diet – Panjang Telomer

Systematic review dan Diet→ tidak Heterogenitas tinggi

meta analysis, 2017 memberikan efek (I2=89%)→ jenis diet
(5 studi, 533 peserta; terhadap panjang dan durasi intervensi
241 kontrol, 18-98th) telomer. berbeda-beda

Pérez LM, Amaral MA, Mundstock E, Barbé-Tuana FM, Guma FTCR, Jones MH, et al. Effects of diet on telomere length: systematic review and meta-
analysis. Public Health Genomics. 2017;20(5):286-92.
44
 Mikronutrien – Panjang Telomer

Defisiensi vit C, E, seng, dan

selenium

Rentan radikal bebas

Oksidasi guanin di TTAGGG

Merusak ikatan telomer

Pérez LM, Amaral MA, Mundstock E, Barbé-Tuana FM, Guma FTCR, Jones MH, et al. Effects of diet on telomere length: systematic review and meta-analysis. Public
Health Genomics. 2017;20(5):286-92.
Vaiserman A, Krasnienkov DS. Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues and Future Perspectives. Frontiers in Genetics.
2020;11:1816 45
 Hasil Penelitian Sangat Beragam

Heterogenitasnya tinggi → disebabkan perbedaan

cara masak, bahan makanan dan etnik

Hasil yang berbeda → banyak faktor confounding

yang menjadi penyulit pada penelitian nutrisi

Perbedaan demografi, gaya hidup, dan hormonal

Rafie N, Hamedani SG, Barak F, Safavi S, Miraghajani M. Dietary patterns, food groups and telomere length: a systematic review of current
studies. European journal of clinical nutrition. 2017;71(2):151-8
46
Kesimpulan
Proses penuaan dipengaruhi oleh genetik dan lingkungan (mis. makanan atau
diet)

Nutrisi mempercepat penuaan (karbohidrat sederhana, processed meat, lemak

jenuh, omega 6, alkohol)

Keadaan terkait penuaan antara lain obesitas, defisiensi mikronutrien (vit C, E,

seng, selenium)

Hasil penelitian nutrisi/diet dengan penuaan memiliki hasil yang berbeda→

banyak confounding

Studi lebih lanjut masih diperlukan, namun healthy life style dapat diterapkan
untuk mengurangi proses inflamasi dan risiko berbagai penyakit metabolik
47
48