老化研究をはじめる前に読む本

出版社： 羊土社
著者：
発行日： 2023-01-01
分野： 基礎医学  >  基礎医学一般
ISBN： 9784758121262
電子書籍版： 2023-01-01 （第1刷）
書籍・雑誌
≪全国送料無料でお届け≫
取寄せ目安：4～8営業日

4,290 円(税込)

購入する
電子書籍
章別単位での購入はできません
ブラウザ、アプリ閲覧

4,290 円(税込)

購入する

商品紹介

これから老化研究に取り組む方必見！必読論文400本以上をまとめ，老化とは何か？から現在わかっている老化のメカニズム，老化治療薬となる可能性がある物質まで丁寧に解説．老化の知識を効率的にアップデート！

目次

  • 第1章　老化とアンチエイジング
    　1-1　老化とは何か
    　1-2　平均寿命と最大寿命
    　1-3　ヒトの老化は抑制できる
    　1-4　老化を抑制すると何が起こるのか
    　1-5　老化研究の方法と注意点
    　1-6　アンチエイジングとは何か
    　1-7　老化研究とアンチエイジングの隆盛
    　　　　老化研究の歩み
    　　　　老化と医学

    第2章　老化のメカニズムについて現在わかっている主な事柄
    　2-1　実は活性酸素と老化との関係性は不明瞭
    　　　　活性酸素の種類
    　　　　活性酸素悪玉説の歴史
    　　　　活性酸素はマウスの老化の主要因でない可能性が高い
    　　　　ミトコンドリアDNAの傷害はマウスの老化の主要な要因でない可能性が高い
    　　　　活性酸素は一部の疾患の発症に重要な役割を担う
    　2-2　テロメアと寿命・疾患の複雑な関係
    　　　　テロメアとテロメラーゼ
    　　　　身体の大きい動物はテロメラーゼ活性の抑制で発がんを防ぐ
    　　　　加齢に伴うテロメアの短小化
    　　　　テロメアが老化や加齢性疾患に及ぼす影響
    　　　　テロメアはその長さとは一部無関係に老化を制御しているかもしれない
    　2-3　代謝と老化の複雑な関係—食事を減らせばよいわけではない
    　　　　成長に資するか，維持に資するか
    　　　　サーチュインとNAD+
    　　　　mTORC1シグナル
    　　　　GH/IGF-1シグナル
    　　　　食事制限と老化
    　2-4　発がん抑制機構「細胞老化」は副次的に老化を促進する
    　　　　細胞老化は発がんリスクを抱えた細胞の増殖を抑制するがん抑制機構である
    　　　　細胞老化を起こした「老化細胞」の蓄積は老化の原因の1つである
    　　　　老化細胞の為害性の原因かもしれない細胞老化随伴分泌現象（SASP）
    　2-5　免疫老化と慢性炎症
    　　　　造血幹細胞の加齢変化
    　　　　T細胞の加齢変化
    　　　　B細胞の加齢変化
    　　　　慢性炎症は老化の大きな特徴である
    　2-6　老化のエラー説とプログラム説
    　　　　プログラムされた老化
    　　　　遺伝子発現パターンの加齢変化は成長と老化の深い結びつきを示唆する
    　　　　エピジェネティック・クロックも成長・成熟・老化の結びつきを示唆する
    　　　　DNAの偶発的損傷と老化
    　　　　DNAの偶発的変異と変異細胞のポジティブセレクション

    第3章　老化治療薬としての可能性が有望視される主要な物質
    　3-1　はじめに
    　3-2　ビタミンD・K
    　3-3　性ホルモン
    　　　　テストステロン
    　　　　エストロゲン
    　3-4　メトホルミン
    　　　　メトホルミンは糖尿病患者の総死亡率を非糖尿病患者以下に押し下げる
    　　　　メトホルミンを老化治療薬として用いていくための取り組み
    　　　　メトホルミンの臓器・細胞レベルの作用
    　　　　メトホルミンがマウスの健康と寿命に及ぼす影響
    　　　　メトホルミンの食欲抑制作用とGDF15
    　　　　メトホルミン，DHEA，そして成長ホルモンの組み合わせによる若返り効果
    　　　　メトホルミンの今後
    　3-5　ラパマイシン
    　　　　ラパマイシンが寿命，健康，そして美容に及ぼす効果
    　　　　ラパマイシンの作用機序と副作用
    　3-6　NAD+ブースター
    　　　　NAD+とその前駆体（NMN，NR，NAM）
    　　　　NAD+前駆体のマウスに対する効果
    　　　　NAD+前駆体のヒトに対する効果
    　　　　その他のNAD+ブースター
    　3-7　セノリティック薬
    　　　　ダサチニブ，ケルセチン，フィセチン
    　　　　その他のセノリティック薬
    　3-8　パーシャルリプログラミング
    　3-9　アンチエイジング研究のこれから
    　　　　その他のアンチエイジング候補物質と注意事項
    　　　　アンチエイジング技術の課題

この書籍の参考文献

参考文献のリンクは、リンク先の都合等により正しく表示されない場合がありますので、あらかじめご了承下さい。

本参考文献は電子書籍掲載内容を元にしております。

第1章 老化とアンチエイジング

P.10 掲載の参考文献
1) McGill HC Jr, et al:Origin of atherosclerosis in childhood and adolescence. Am J Clin Nutr, 72:1307S-1315S, 2000(PMID:11063473)
 
2) de Magalhaes JP:Programmatic features of aging originating in development: aging mechanisms beyond molecular damage? FASEB J, 26:4821-4826, 2012(PMID:22964300)
 
3) Dong X, et al:Evidence for a limit to human lifespan. Nature, 538:257-259, 2016(PMID:27706136)
 
4) Riley JC:Estimates of Regional and Global Life Expectancy, 1800-2001. Popul Dev Rev, 31:537-543, 2005
 
P.12 掲載の参考文献
5) Wang C, et al:Statistical methods for testing effects on"maximum lifespan". Mech Ageing Dev, 125:629-632, 2004(PMID:15491681)
 
P.14 掲載の参考文献
6) Schwingshackl L, et al:Food groups and risk of all-cause mortality: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr, 105:1462-1473, 2017(PMID:28446499)
 
7) GBD 2017 Diet Collaborators:Health effects of dietary risks in 195 countries, 1990-2017:a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 393:1958-1972, 2019(PMID:30954305)
 
8) Zhu H, et al:High sodium intake is associated with short leukocyte telomere length in overweight and obese adolescents. Int J Obes (Lond), 39:1249-1253, 2015(PMID:25869605)
 
9) Bannister CA, et al:Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea mono-therapy and matched, non-diabetic controls. Diabetes Obes Metab, 16:1165-1173, 2014(PMID:25041462)
 
10) Kulkarni AS, et al:Benefits of Metformin in Attenuating the Hallmarks of Aging. Cell Metab, 32:15-30, 2020(PMID:32333835)
 
P.16 掲載の参考文献
11) Goldman DP, et al:Substantial health and economic returns from delayed aging may war-rant a new focus for medical research. Health Aff (Millwood), 32:1698-1705, 2013(PMID:24101058)
 
12) Andersen SL, et al:Health span approximates life span among many supercentenarians:compression of morbidity at the approximate limit of life span. J Gerontol A Biol Sci Med Sci, 67:395-405, 2012(PMID:22219514)
 
13) Miller RA:Extending life: scientific prospects and political obstacles. Milbank Q, 80:155-174, 2002(PMID:11933792)
 
14) Olshansky SJ, et al:In search of Methuselah: estimating the upper limits to human lon-gevity. Science, 250:634-640, 1990(PMID:2237414)
 
P.18 掲載の参考文献
15) Nakamura M, et al:Mitochondrial defects trigger proliferation of neighbouring cells via a senescence-associated secretory phenotype in Drosophila. Nat Commun, 5:5264, 2014(PMID:25345385)
 
16) Imai S, et al:Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature, 403:795-800, 2000(PMID:10693811)
 
17) Liao CY, et al:Genetic variation in the murine lifespan response to dietary restriction:from life extension to life shortening. Aging Cell, 9:92-95, 2010(PMID:19878144)
 
18) Flurkey K, et al:Chapter 20 - Mouse Models in Aging Research.「The-Mouse-in Biomed-ical Research 2nd edition, Volume 3: Normative Biology, Husbandry, and Models」(Fox JG, et al, eds), 637-672, Academic Press, 2007
 
19) Schaum N, et al:Ageing hallmarks exhibit organ-specific temporal signatures. Nature, 583:596-602, 2020(PMID:32669715)
 
P.23 掲載の参考文献
20) Campisi J, et al:From discoveries in ageing research to therapeutics for healthy ageing. Nature, 571:183-192, 2019(PMID:31292558)
 

第2章 老化のメカニズムについて現在わかっている主な事柄

P.30 掲載の参考文献
21) Harman D:Aging: a theory based on free radical and radiation chemistry. J Gerontol, 11:298-300, 1956(PMID:13332224)
 
22) Salmon AB, et al:Update on the oxidative stress theory of aging: does oxidative stress play a role in aging or healthy aging? Free Radic Biol Med, 48:642-655, 2010(PMID:20036736)
 
23) Doonan R, et al:Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev, 22:3236-3241, 2008(PMID:19056880)
 
24) Van Raamsdonk JM & Hekimi S:Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet, 5:e1000361, 2009(PMID:19197346)
 
25) Van Remmen H, et al:Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics, 16:29-37, 2003(PMID:14679299)
 
26) Jang YC, et al:Overexpression of Mn superoxide dismutase does not increase life span in mice. J Gerontol A Biol Sci Med Sci, 64:1114-1125, 2009(PMID:19633237)
 
27) Zhang Y, et al:Mice deficient in both Mn superoxide dismutase and glutathione peroxi-dase-1 have increased oxidative damage and a greater incidence of pathology but no reduction in longevity. J Gerontol A Biol Sci Med Sci, 64:1212-1220, 2009(PMID:19776219)
 
28) Perez VI, et al:Is the oxidative stress theory of aging dead? Biochim Biophys Acta, 1790:1005-1014, 2009(PMID:19524016)
 
29) Perez VI, et al:The overexpression of major antioxidant enzymes does not extend the lifespan of mice. Aging Cell, 8:73-75, 2009(PMID:19077044)
 
30) Pang WW, et al:Human bone marrow hematopoietic stem cells are increased in fre-quency and myeloid-biased with age. Proc Natl Acad Sci U S A, 108:20012-20017, 2011(PMID:22123971)
 
31) Sentman ML, et al:Phenotypes of mice lacking extracellular superoxide dismutase and copper- and zinc-containing superoxide dismutase. J Biol Chem, 281:6904-6909, 2006(PMID:16377630)
 
32) Salmon AB, et al:Lack of methionine sulfoxide reductase A in mice increases sensitivity to oxidative stress but does not diminish life span. FASEB J, 23:3601-3608, 2009(PMID:19487311)
 
33) Perez VI, et al:Thioredoxin 2 haploinsufficiency in mice results in impaired mitochon-drial function and increased oxidative stress. Free Radic Biol Med, 44:882-892, 2008(PMID:18164269)
 
34) Mitsui A, et al:Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span. Antioxid Redox Signal, 4:693-696, 2002(PMID:12230882)
 
35) Schriner SE, et al:Extension of murine life span by overexpression of catalase targeted to mitochondria. Science, 308:1909-1911, 2005(PMID:15879174)
 
P.32 掲載の参考文献
36) Miquel J, et al:Mitochondrial role in cell aging. Exp Gerontol, 15:575-591, 1980(PMID:7009178)
 
37) Fleming JE, et al:Is cell aging caused by respiration-dependent injury to the mitochon-drial genome? Gerontology, 28:44-53, 1982(PMID:7037547)
 
38) Vermulst M, et al:Mitochondrial point mutations do not limit the natural lifespan of mice. Nat Genet, 39:540-543, 2007(PMID:17334366)
 
39) Tyynismaa H, et al:Mutant mitochondrial helicase Twinkle causes multiple mtDNA dele-tions and a late-onset mitochondrial disease in mice. Proc Natl Acad Sci U S A, 102:17687-17692, 2005(PMID:16301523)
 
P.33 掲載の参考文献
40) Li D & Mehta JL:Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells. Circulation, 101:2889-2895, 2000(PMID:10869259)
 
41) Linton MRF, et al:The Role of Lipids and Lipoproteins in Atherosclerosis. Endotext [Internet], Last Update 2019(https://www.ncbi.nlm.nih.gov/books/NBK343489/)(PMID:26844337)
 
42) Glavind J, et al:Studies on the role of lipoperoxides in human pathology. II. The presence of peroxidized lipids in the atherosclerotic aorta. Acta Pathol Microbiol Scand, 30: 1-6, 1952(PMID:14933036)
 
43) Suarna C, et al:Human atherosclerotic plaque contains both oxidized lipids and relatively large amounts of alpha-tocopherol and ascorbate. Arterioscler Thromb Vasc Biol, 15:1616-1624, 1995(PMID:7583535)
 
44) Salomon RG, et al:HNE-derived 2-pentylpyrroles are generated during oxidation of LDL, are more prevalent in blood plasma from patients with renal disease or atherosclerosis, and are present in atherosclerotic plaques. Chem Res Toxicol, 13:557-564, 2000(PMID:10898587)
 
45) Li D & Mehta JL:Oxidized LDL, a critical factor in atherogenesis. Cardiovasc Res, 68:353-354, 2005(PMID:16253212)
 
46) Forman HJ & Zhang H:Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov, 20:689-709, 2021(PMID:34194012)
 
P.34 掲載の参考文献
b1) Buffenstein R:The naked mole-rat: a new long-living model for human aging research. J Gerontol A Biol Sci Med Sci, 60:1369-1377, 2005(PMID:16339321)
 
b2) Ruby JG, et al:Naked Mole-Rat mortality rates defy gompertzian laws by not increasing with age. Elife, 7:e31157, 2018(PMID:29364116)
 
b3) O'Connor TP, et al:Prolonged longevity in naked mole-rats: age-related changes in metabolism, body composition and gastrointestinal function. Comp Biochem Physiol A Mol Integr Physiol, 133:835-842, 2002(PMID:12443939)
 
b4) Buffenstein R:Negligible senescence in the longest living rodent, the naked mole-rat:insights from a successfully aging species. J Comp Physiol B, 178:439-445, 2008(PMID:18180931)
 
b5) Edrey YH, et al:Successful aging and sustained good health in the naked mole rat: a long-lived mammalian model for biogerontology and biomedical research. ILAR J, 52:41-53,2011(PMID:21411857)
 
b6) Grimes KM, et al:And the beat goes on: maintained cardiovascular function during aging in the longest-lived rodent, the naked mole-rat. Am J Physiol Heart Circ Physiol, 307:H284-H291, 2014(PMID:24906918)
 
P.37 掲載の参考文献
47) Seluanov A, et al:Telomerase activity coevolves with body mass not lifespan. Aging Cell, 6:45-52, 2007(PMID:17173545)
 
48) Seluanov A, et al:Distinct tumor suppressor mechanisms evolve in rodent species that differ in size and lifespan. Aging Cell, 7:813-823, 2008(PMID:18778411)
 
49) Tian X, et al:Evolution of telomere maintenance and tumour suppressor mechanisms across mammals. Philos Trans R Soc Lond B Biol Sci, 373:doi: 10.1098/rstb.2016.0443, 2018(PMID:29335367)
 
50) Shay JW & Bacchetti S:A survey of telomerase activity in human cancer. Eur J Cancer, 33:787-791, 1997(PMID:9282118)
 
P.38 掲載の参考文献
51) Bergmann O, et al:Dynamics of Cell Generation and Turnover in the Human Heart. Cell, 161:1566-1575, 2015(PMID:26073943)
 
52) Litvinukova M, et al:Cells of the adult human heart. Nature, 588:466-472, 2020(PMID:32971526)
 
53) Spalding KL, et al:Retrospective birth dating of cells in humans. Cell, 122:133-143, 2005(PMID:16009139)
 
54) Yeung MS, et al:Dynamics of oligodendrocyte generation and myelination in the human brain. Cell, 159:766-774, 2014(PMID:25417154)
 
55) Colodner KJ, et al:Proliferative potential of human astrocytes. J Neuropathol Exp Neurol, 64:163-169, 2005(PMID:15751231)
 
56) Terai M, et al:Association of telomere shortening in myocardium with heart weight gain and cause of death. Sci Rep, 3:2401, 2013(PMID:23929129)
 
57) Tomita KI, et al:Changes in telomere length with aging in human neurons and glial cells revealed by quantitative fluorescence in situ hybridization analysis. Geriatr Gerontol Int, 18:1507-1512, 2018(PMID:30095207)
 
58) Heinke P, et al:Diploid hepatocytes drive physiological liver renewal in adult humans. Cell Syst, 13:499-507.e12, 2022(PMID:35649419)
 
59) Wiemann SU, et al:Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. FASEB J, 16:935-942, 2002(PMID:12087054)
 
60) von Zglinicki T:Oxidative stress shortens telomeres. Trends Biochem Sci, 27:339-344, 2002(PMID:12114022)
 
61) Boonekamp JJ, et al:Does oxidative stress shorten telomeres? Biol Lett, 13:doi:10.1098/rsbl.2017.0164, 2017(PMID:28468913)
 
62) Demanelis K, et al:Determinants of telomere length across human tissues. Science, 369:doi:10.1126/science.aaz6876, 2020(PMID:32913074)
 
63) Daniali L, et al:Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Commun, 4:1597, 2013(PMID:23511462)
 
64) Ouellette MM, et al:Subsenescent telomere lengths in fibroblasts immortalized by lim-iting amounts of telomerase. J Biol Chem, 275:10072-10076, 2000(PMID:10744686)
 
65) Ornish D, et al:Effect of comprehensive lifestyle changes on telomerase activity and telo-mere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. Lancet Oncol, 14:1112-1120, 2013(PMID:24051140)
 
P.40 掲載の参考文献
66) Lee DC, et al:Effect of long-term hormone therapy on telomere length in postmenopausal women. Yonsei Med J, 46:471-479, 2005(PMID:16127770)
 
67) Wang Q, et al:Telomere Length and All-Cause Mortality: A Meta-analysis. Ageing Res Rev, 48:11-20, 2018(PMID:30254001)
 
68) Codd V, et al:Polygenic basis and biomedical consequences of telomere length variation. Nat Genet, 53:1425-1433, 2021(PMID:34611362)
 
69) Rudolph KL, et al:Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell, 96:701-712, 1999(PMID:10089885)
 
70) Bernardes de Jesus B, et al:Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol Med, 4:691-704, 2012(PMID:22585399)
 
71) Segal-Bendirdjian E & Geli V:Non-canonical Roles of Telomerase: Unraveling the Imbro-glio. Front Cell Dev Biol, 7:332, 2019(PMID:31911897)
 
P.42 掲載の参考文献
72) Fumagalli M, et al:Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat Cell Biol, 14:355-365, 2012(PMID:22426077)
 
73) Hewitt G, et al:Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat Commun, 3:708, 2012(PMID:22426229)
 
74) Anderson R, et al:Length-independent telomere damage drives post-mitotic cardiomyo-cyte senescence. EMBO J, 38:e100492, 2019(PMID:30737259)
 
P.44 掲載の参考文献
75) Grabowska W, et al:Sirtuins, a promising target in slowing down the ageing process. Biogerontology, 18:447-476, 2017(PMID:28258519)
 
76) Wang P, et al:Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway. Ann Neurol, 69:360-374, 2011(PMID:21246601)
 
77) Canto C, et al:AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature, 458:1056-1060, 2009(PMID:19262508)
 
78) Herranz D, et al:Sirt1 improves healthy ageing and protects from metabolic syndrome-as-sociated cancer. Nat Commun, 1:3, 2010(PMID:20975665)
 
79) Jeong H, et al:Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway. Nat Med, 18:159-165, 2011(PMID:22179316)
 
80) Satoh A, et al:Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab, 18:416-430, 2013(PMID:24011076)
 
81) Giblin W, et al:Sirtuins: guardians of mammalian healthspan. Trends Genet, 30:271-286, 2014(PMID:24877878)
 
82) Alcendor RR, et al:Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res, 100:1512-1521, 2007(PMID:17446436)
 
83) Zhao Y, et al:Cytosolic FoxO1 is essential for the induction of autophagy and tumour sup-pressor activity. Nat Cell Biol, 12:665-675, 2010(PMID:20543840)
 
84) Martins R, et al:Long live FOXO: unraveling the role of FOXO proteins in aging and lon-gevity. Aging Cell, 15:196-207, 2016(PMID:26643314)
 
85) Wang Y, et al:SIRT2: Controversy and multiple roles in disease and physiology. Ageing Res Rev, 55:100961, 2019(PMID:31505260)
 
86) Polito L, et al:The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts. Alzheimers Dement, 9:392-399, 2013(PMID:22651940)
 
87) Ma XR, et al:Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells pro-motes remyelination during ageing. Nat Commun, 13:1225, 2022(PMID:35264567)
 
88)Bellizzi D, et al:A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics, 85:258-263, 2005(PMID:15676284)
 
89) TenNapel MJ, et al:SIRT6 minor allele genotype is associated with >5-year decrease in lifespan in an aged cohort. PLoS One, 9:e115616, 2014(PMID:25541994)
 
90) Simon M, et al:A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A. EMBO J:e110393, 2022 (PMID:36215696)
 
91) Lin R, et al:Lack of association between polymorphisms in the SIRT6 gene and longevity in a Chinese population. Mol Cell Probes, 30:79-82, 2016(PMID:26802595)
 
92) Sundaresan NR, et al:Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest, 119:2758-2771, 2009(PMID:19652361)
 
93) Mao Z, et al:SIRT6 promotes DNA repair under stress by activating PARP1. Science, 332:1443-1446, 2011(PMID:21680843)
 
94) Michishita E, et al:SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature, 452:492-496, 2008(PMID:18337721)
 
95) Van Meter M, et al:SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age. Nat Commun, 5:5011, 2014(PMID:25247314)
 
96) Roichman A, et al:Restoration of energy homeostasis by SIRT6 extends healthy lifespan. Nat Commun, 12:3208, 2021(PMID:34050173)
 
97) Simon M, et al:LINE1 Derepression in Aged Wild-Type and SIRT6-Deficient Mice Drives Inflammation. Cell Metab, 29:871-885.e5, 2019(PMID:30853213)
 
98) Kanfi Y, et al:The sirtuin SIRT6 regulates lifespan in male mice. Nature, 483:218-221, 2012(PMID:22367546)
 
99) Vakhrusheva O, et al:Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circ Res, 102:703-710, 2008(PMID:18239138)
 
100) Mohrin M, et al:Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging. Science, 347:1374-1377, 2015(PMID:25792330)
 
101) Yoshino J, et al:NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab, 27:513-528, 2018(PMID:29249689)
 
102) Massudi H, et al:Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One, 7:e42357, 2012(PMID:22848760)
 
103) Zhou CC, et al:Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. Br J Pharmacol, 173:2352-2368, 2016(PMID:27174364)
 
104) Zhu XH, et al:In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci U S A, 112:2876-2881, 2015(PMID:25730862)
 
105) Janssens GE, et al:Healthy aging and muscle function are positively associated with NAD+ abundance in humans. Nature Aging, 2:254-263, 2022
 
106) Clement J, et al:The Plasma NAD+ Metabolome Is Dysregulated in"Normal"Aging. Rejuvenation Res, 22:121-130, 2019(PMID:30124109)
 
107) Minhas PS, et al:Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation. Nat Immunol, 20:50-63, 2019(PMID:30478397)
 
P.49 掲載の参考文献
108) Harrison DE, et al:Rapamycin fed late in life extends lifespan in genetically heteroge-neous mice. Nature, 460:392-395, 2009(PMID:19587680)
 
109) Neff F, et al:Rapamycin extends murine lifespan but has limited effects on aging. J Clin Invest, 123:3272-3291, 2013(PMID:23863708)
 
110) Bitto A, et al:Transient rapamycin treatment can increase lifespan and healthspan in mid-dle-aged mice. Elife, 5:e16351, 2016(PMID:27549339)
 
111) Strong R, et al:Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects. Aging Cell, 19:e13269, 2020(PMID:33145977)
 
112) Lamming DW, et al:Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science, 335:1638-1643, 2012(PMID:22461615)
 
113) Selman C, et al:Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science, 326:140-144, 2009(PMID:19797661)
 
114) Wu JJ, et al:Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep, 4:913-920, 2013(PMID:23994476)
 
P.51 掲載の参考文献
115) Bartke A, et al:Extending the lifespan of long-lived mice. Nature, 414:412, 2001(PMID:11719795)
 
116) Flurkey K, et al:Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci U S A, 98:6736-6741, 2001(PMID:11371619)
 
117) Coschigano KT, et al:Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology, 141:2608-2613, 2000(PMID:10875265)
 
118) Selman C, et al:Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J, 22:807-818, 2008(PMID:17928362)
 
119) Taguchi A, et al:Brain IRS2 signaling coordinates life span and nutrient homeostasis. Sci-ence, 317:369-372, 2007(PMID:17641201)
 
120) Holzenberger M, et al:IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature, 421:182-187, 2003(PMID:12483226)
 
121) Yakar S, et al:Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity. Dia-betes, 50:1110-1118, 2001(PMID:11334415)
 
122) Gong Z, et al:Reductions in serum IGF-1 during aging impair health span. Aging Cell, 13:408-418, 2014(PMID:24341939)
 
123) Rudman D, et al:Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest, 67:1361-1369, 1981(PMID:7194884)
 
124) Yamamoto H, et al:Effects of aging and sex on plasma insulin-like growth factor I (IGF-I) levels in normal adults. Acta Endocrinol (Copenh), 124:497-500, 1991(PMID:2028707)
 
125) Rudman D, et al:Effects of human growth hormone in men over 60 years old. N Engl J Med, 323:1-6, 1990(PMID:2355952)
 
126) Kaplan RC, et al:Decline in circulating insulin-like growth factors and mortality in older adults: cardiovascular health study all-stars study. J Clin Endocrinol Metab, 97:1970-1976, 2012(PMID:22442270)
 
127) Sun LY, et al:Longevity is impacted by growth hormone action during early postnatal period. Elife, 6:e24059, 2017(PMID:28675141)
 
128) Duran-Ortiz S, et al:Growth hormone receptor gene disruption in mature-adult mice improves male insulin sensitivity and extends female lifespan. Aging Cell, 20:e13506, 2021(PMID:34811874)
 
129) Mao K, et al:Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice. Nat Commun, 9:2394, 2018(PMID:29921922)
 
130) Milman S, et al:The Somatotropic Axis in Human Aging: Framework for the Current State of Knowledge and Future Research. Cell Metab, 23:980-989, 2016(PMID:27304500)
 
131) Andreassen M, et al:IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population. Eur J Endocrinol, 160:25-31, 2009(PMID:18931092)
 
132) Burgers AM, et al:Meta-analysis and dose-response metaregression: circulating insu-lin-like growth factor I (IGF-I) and mortality. J Clin Endocrinol Metab, 96:2912-2920, 2011(PMID:21795450)
 
133) Svensson J, et al:Both low and high serum IGF-I levels associate with cancer mortality in older men. J Clin Endocrinol Metab, 97:4623-4630, 2012(PMID:23015658)
 
134) Rahmani J, et al:Association between IGF-1 levels ranges and all-cause mortality: A meta-analysis. Aging Cell, 21:e13540, 2022(PMID:35048526)
 
135) Saydah S, et al:Insulin-like growth factors and subsequent risk of mortality in the United States. Am J Epidemiol, 166:518-526, 2007(PMID:17602136)
 
136) Maggio M, et al:Relationship between low levels of anabolic hormones and 6-year mor-tality in older men: the aging in the Chianti Area (InCHIANTI) study. Arch Intern Med, 167:2249-2254, 2007(PMID:17998499)
 
137) Milman S, et al:Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell, 13:769-771, 2014(PMID:24618355)
 
138) van Heemst D, et al:Reduced insulin/IGF-1 signalling and human longevity. Aging Cell, 4:79-85, 2005(PMID:15771611)
 
139) Suh Y, et al:Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci U S A, 105:3438-3442, 2008(PMID:18316725)
 
140) Ben-Avraham D, et al:The GH receptor exon 3 deletion is a marker of male-specific exceptional longevity associated with increased GH sensitivity and taller stature. Sci Adv, 3:e1602025, 2017(PMID:28630896)
 
141) Samaras TT, et al:Is height related to longevity? Life Sci, 72:1781-1802, 2003(PMID: 12586217)
 
P.55 掲載の参考文献
142) McCracken AW, et al:The hidden costs of dietary restriction: Implications for its evolu-tionary and mechanistic origins. Sci Adv, 6:eaay3047, 2020(PMID:32128403)
 
143) Colman RJ, et al:Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325:201-204, 2009(PMID:19590001)
 
144) Mattison JA, et al:Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature, 489:318-321, 2012(PMID:22932268)
 
145) Mattison JA, et al:Caloric restriction improves health and survival of rhesus monkeys. Nat Commun, 8:14063, 2017(PMID:28094793)
 
146) Redman LM, et al:Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging. Cell Metab, 27:805-815.e4, 2018(PMID:29576535)
 
147) Lefevre M, et al:Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis, 203:206-213, 2009(PMID:18602635)
 
148) Meydani SN, et al:Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans. Aging (Albany NY), 8:1416-1431, 2016(PMID:27410480)
 
149) Spadaro O, et al:Caloric restriction in humans reveals immunometabolic regulators of health span. Science, 375:671-677, 2022(PMID:35143297)
 
150) Flanagan EW, et al:Calorie Restriction and Aging in Humans. Annu Rev Nutr, 40:105-133, 2020(PMID:32559388)
 
151) Wilson KA, et al:Evaluating the beneficial effects of dietary restrictions: A framework for precision nutrigeroscience. Cell Metab, 33:2142-2173, 2021(PMID:34555343)
 
152) Weiss EP, et al:Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss. J Appl Physiol (1985), 102:634-640, 2007(PMID:17095635)
 
153) Waziry R, et al:Effect of Long-Term Caloric Restriction on DNA Methylation Measures of Biological Aging in Healthy Adults: CALERIE(TM) Trial Analysis. medRxiv, doi:10.1101/2021. 09.21.21263912, 2021
 
154) Aune D, et al:BMI and all cause mortality: systematic review and non-linear dose-re-sponse meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants. BMJ, 353:i2156, 2016(PMID:27146380)
 
155) Winter JE, et al:BMI and all-cause mortality in older adults: a meta-analysis. Am J Clin Nutr, 99:875-890, 2014(PMID:24452240)
 
156) Solon-Biet SM, et al:The ratio of macronutrients, not caloric intake, dictates cardiometa-bolic health, aging, and longevity in ad libitum-fed mice. Cell Metab, 19:418-430, 2014(PMID:24606899)
 
157) Orentreich N, et al:Low methionine ingestion by rats extends life span. J Nutr, 123:269-274, 1993(PMID:8429371)
 
158) Miller RA, et al:Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell, 4:119-125, 2005(PMID:15924568)
 
159) De Marte ML & Enesco HE:Influence of low tryptophan diet on survival and organ growth in mice. Mech Ageing Dev, 36:161-171, 1986(PMID:3784629)
 
160) Brown-Borg HM & Buffenstein R:Cutting back on the essentials: Can manipulating intake of specific amino acids modulate health and lifespan? Ageing Res Rev, 39:87-95, 2017(PMID:27570078)
 
161) Speakman JR, et al:Calories or protein? The effect of dietary restriction on lifespan in rodents is explained by calories alone. Exp Gerontol, 86:28-38, 2016(PMID:27006163)
 
162) Levine ME, et al:Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab, 19:407-417, 2014(PMID:24606898)
 
163) Seidelmann SB, et al:Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis. Lancet Public Health, 3:e419-e428, 2018(PMID:30122560)
 
164) Soare A, et al:Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans. Aging (Albany NY), 3:374-379, 2011(PMID:21483032)
 
165) Koizumi A, et al:A tumor preventive effect of dietary restriction is antagonized by a high housing temperature through deprivation of torpor. Mech Ageing Dev, 92:67-82, 1996(PMID:9032756)
 
166) Conti B, et al:Transgenic mice with a reduced core body temperature have an increased life span. Science, 314:825-828, 2006(PMID:17082459)
 
167) Harrison DE, et al:Effects of food restriction on aging: separation of food intake and adi-posity. Proc Natl Acad Sci U S A, 81:1835-1838, 1984(PMID:6608731)
 
P.60 掲載の参考文献
168) Rodier F, et al:DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion. J Cell Sci, 124:68-81, 2011(PMID:21118958)
 
169) Di Micco R, et al:Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature, 444:638-642, 2006(PMID:17136094)
 
170) Collado M, et al:Tumour biology: senescence in premalignant tumours. Nature, 436:642, 2005(PMID:16079833)
 
171) Chen Z, et al:Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature, 436:725-730, 2005(PMID:16079851)
 
172) Michaloglou C, et al:BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature, 436:720-724, 2005(PMID:16079850)
 
173) Jacks T, et al:Tumor spectrum analysis in p53-mutant mice. Curr Biol, 4:1-7, 1994(PMID:7922305)
 
174) Martin-Caballero J, et al:Tumor susceptibility of p21(Waf1/Cip1)-deficient mice. Cancer Res, 61:6234-6238, 2001(PMID:11507077)
 
175) Sharpless NE, et al:Loss of p16Ink4a with retention of p19Arf predisposes mice to tumor-igenesis. Nature, 413:86-91, 2001(PMID:11544531)
 
176) Jun JI & Lau LF:The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat Cell Biol, 12:676-685, 2010(PMID:20526329)
 
177) Demaria M, et al:An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell, 31:722-733, 2014(PMID:25499914)
 
178) Krizhanovsky V, et al:Senescence of activated stellate cells limits liver fibrosis. Cell, 134:657-667, 2008(PMID:18724938)
 
179) Munoz-Espin D, et al:Programmed cell senescence during mammalian embryonic devel-opment. Cell, 155:1104-1118, 2013(PMID:24238962)
 
180) Storer M, et al:Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell, 155:1119-1130, 2013(PMID:24238961)
 
P.62 掲載の参考文献
181) Krishnamurthy J, et al:Ink4a/Arf expression is a biomarker of aging. J Clin Invest, 114:1299-1307, 2004(PMID:15520862)
 
182) Yamakoshi K, et al:Real-time in vivo imaging of p16Ink4a reveals cross talk with p53. J Cell Biol, 186:393-407, 2009(PMID:19667129)
 
183) Ressler S, et al:p16INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell, 5:379-389, 2006(PMID:16911562)
 
184) Liu Y, et al:Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell, 8:439-448, 2009(PMID:19485966)
 
185) Idda ML, et al:Survey of senescent cell markers with age in human tissues. Aging (Albany NY), 12:4052-4066, 2020(PMID:32160592)
 
186) Gorgoulis V, et al:Cellular Senescence: Defining a Path Forward. Cell, 179:813-827, 2019(PMID:31675495)
 
187) Prata LGPL, et al:Senescent cell clearance by the immune system: Emerging therapeutic opportunities. Semin Immunol, 40:101275, 2018(PMID:31088710)
 
188) Yousefzadeh MJ, et al:An aged immune system drives senescence and ageing of solid organs. Nature, 594:100-105, 2021(PMID:33981041)
 
189) Nyunoya T, et al:Cigarette smoke induces cellular senescence. Am J Respir Cell Mol Biol, 35:681-688, 2006(PMID:16840774)
 
190) Yoshimoto S, et al:Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature, 499:97-101, 2013(PMID:23803760)
 
191) Janzen V, et al:Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature, 443:421-426, 2006(PMID:16957735)
 
192) Sousa-Victor P, et al:Geriatric muscle stem cells switch reversible quiescence into senes-cence. Nature, 506:316-321, 2014(PMID:24522534)
 
193) Baker DJ, et al:Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature, 530:184-189, 2016(PMID:26840489)
 
194) Childs BG, et al:Senescent intimal foam cells are deleterious at all stages of atheroscle-rosis. Science, 354:472-477, 2016(PMID:27789842)
 
195) Ogrodnik M, et al:Cellular senescence drives age-dependent hepatic steatosis. Nat Commun, 8:15691, 2017(PMID:28608850)
 
196) Aguayo-Mazzucato C, et al:Acceleration of β Cell Aging Determines Diabetes and Seno-lysis Improves Disease Outcomes. Cell Metab, 30:129-142.e4, 2019(PMID:31155496)
 
197) Chang J, et al:Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med, 22:78-83, 2016(PMID:26657143)
 
198) Baar MP, et al:Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell, 169:132-147.e16, 2017(PMID:28340339)
 
199) Johmura Y, et al:Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science, 371:265-270, 2021(PMID:33446552)
 
200) Yousefzadeh MJ, et al:Fisetin is a senotherapeutic that extends health and lifespan. EBio-Medicine, 36:18-28, 2018(PMID:30279143)
 
201) Xu M, et al:Senolytics improve physical function and increase lifespan in old age. Nat Med, 24:1246-1256, 2018(PMID:29988130)
 
P.64 掲載の参考文献
202) Dimri GP, et al:A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A, 92:9363-9367, 1995(PMID:7568133)
 
203) Coppe JP, et al:Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol, 6:2853-2868, 2008(PMID:19053174)
 
204) Basisty N, et al:A proteomic atlas of senescence-associated secretomes for aging bio-marker development. PLoS Biol, 18:e3000599, 2020(PMID:31945054)
 
205) Coppe JP, et al:The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol, 5:99-118, 2010(PMID:20078217)
 
206) Rodier F, et al:Persistent DNA damage signalling triggers senescence-associated inflam-matory cytokine secretion. Nat Cell Biol, 11:973-979, 2009(PMID:19597488)
 
207) Chien Y, et al:Control of the senescence-associated secretory phenotype by NF- κ B pro-motes senescence and enhances chemosensitivity. Genes Dev, 25:2125-2136, 2011(PMID:21979375)
 
208) Adler AS, et al:Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev, 21:3244-3257, 2007(PMID:18055696)
 
209) Pribluda A, et al:A senescence-inflammatory switch from cancer-inhibitory to can-cer-promoting mechanism. Cancer Cell, 24:242-256, 2013(PMID:23890787)
 
210) Acosta JC, et al:A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol, 15:978-990, 2013(PMID:23770676)
 
211) Faget DV, et al:Unmasking senescence: context-dependent effects of SASP in cancer. Nat Rev Cancer, 19:439-453, 2019(PMID:31235879)
 
212) Kortlever RM, et al:Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat Cell Biol, 8:877-884, 2006(PMID:16862142)
 
213) Acosta JC, et al:Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell, 133:1006-1018, 2008(PMID:18555777)
 
214) Wajapeyee N, et al:Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell, 132:363-374, 2008(PMID:18267069)
 
215) Kuilman T, et al:Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell, 133:1019-1031, 2008(PMID:18555778)
 
216) Takasugi M, et al:Cellular senescence and the tumour microenvironment. Mol Oncol:doi:10.1002/1878-0261.13268, 2022(PMID:35674109)
 
217) Wang L, et al:Exploiting senescence for the treatment of cancer. Nat Rev Cancer, 22:340-355, 2022(PMID:35241831)
 
P.67 掲載の参考文献
b7) Obermeyer Z, et al:Individual differences in normal body temperature: longitudinal big data analysis of patient records. BMJ, 359:j5468, 2017(PMID:29237616)
 
b8) Keil G, et al:Being cool: how body temperature influences ageing and longevity. Biogeron-tology, 16:383-397, 2015(PMID:25832892)
 
b9) Horvath S, et al:DNA methylation clocks tick in naked mole rats but queens age more slowly than nonbreeders. Nat Aging, 2:46-59, 2022(PMID:35368774)
 
P.68 掲載の参考文献
218) Alpert A, et al:A clinically meaningful metric of immune age derived from high-dimen-sional longitudinal monitoring. Nat Med, 25:487-495, 2019(PMID:30842675)
 
219) Geiger H, et al:The ageing haematopoietic stem cell compartment. Nat Rev Immunol, 13:376-389, 2013(PMID:23584423)
 
220) Jaiswal S, et al:Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med, 371:2488-2498, 2014(PMID:25426837)
 
221) Zink F, et al:Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood, 130:742-752, 2017(PMID:28483762)
 
222) Jaiswal S, et al:Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med, 377:111-121, 2017(PMID:28636844)
 
223) de Haan G & Lazare SS:Aging of hematopoietic stem cells. Blood, 131:479-487, 2018(PMID:29141947)
 
224) Allsopp RC, et al:Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells. Nat Med, 9:369-371, 2003(PMID:12669037)
 
225) Mitchell E, et al:Clonal dynamics of haematopoiesis across the human lifespan. Nature, 606:343-350, 2022 (PMID:35650442)
 
226) Florian MC, et al:Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell Stem Cell, 10:520-530, 2012(PMID:22560076)
 
227) Amoah A, et al:Aging of human hematopoietic stem cells is linked to changes in Cdc42 activity. Haematologica, 107:393-402, 2022(PMID:33440922)
 
228) Florian MC, et al:Expression and Activity of the Small RhoGTPase Cdc42 in Blood Cells of Older Adults Are Associated With Age and Cardiovascular Disease. J Gerontol A Biol Sci Med Sci, 72:1196-1200, 2017(PMID:28498918)
 
229) Florian MC, et al:A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing. Nature, 503:392-396, 2013(PMID:24141946)
 
230) Wang L, et al:Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes. Proc Natl Acad Sci U S A, 104:1248-1253, 2007(PMID:17227869)
 
231) Florian MC, et al:Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice. Aging Cell, 19:e13208, 2020(PMID:32755011)
 
232) Kerber RA, et al:Gene expression profiles associated with aging and mortality in humans. Aging Cell, 8:239-250, 2009(PMID:19245677)
 
233) Ho TT, et al:Autophagy maintains the metabolism and function of young and old stem cells. Nature, 543:205-210, 2017(PMID:28241143)
 
P.70 掲載の参考文献
234) Bains I, et al:Quantifying the development of the peripheral naive CD4+ T-cell pool in humans. Blood, 113:5480-5487, 2009(PMID:19179300)
 
235) Czesnikiewicz-Guzik M, et al:T cell subset-specific susceptibility to aging. Clin Immunol, 127:107-118, 2008(PMID:18222733)
 
236) Zhang H, et al:Hallmarks of the aging T-cell system. FEBS J, 288:7123-7142, 2021(PMID:33590946)
 
237) Koch S, et al:Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people. Immun Ageing, 5:6, 2008(PMID:18657274)
 
238) Weng NP, et al:CD28(-) T cells: their role in the age-associated decline of immune func-tion. Trends Immunol, 30:306-312, 2009(PMID:19540809)
 
239) Zhang J, et al:Senescent T cells: a potential biomarker and target for cancer therapy. EBio-Medicine, 68:103409, 2021(PMID:34049248)
 
240) Wertheimer AM, et al:Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans. J Immunol, 192:2143-2155, 2014(PMID:24501199)
 
241) Khan N, et al:Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol, 169:1984-1992, 2002(PMID:12165524)
 
242) Britanova OV, et al:Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling. J Immunol, 192:2689-2698, 2014(PMID:24510963)
 
243) Sprent J & Surh CD:Normal T cell homeostasis: the conversion of naive cells into memo-ry-phenotype cells. Nat Immunol, 12:478-484, 2011(PMID:21739670)
 
244) Chiu BC, et al:Cutting edge: Central memory CD8 T cells in aged mice are virtual memory cells. J Immunol, 191:5793-5796, 2013(PMID:24227783)
 
245) Martinez-Zamudio RI, et al:Senescence-associated β-galactosidase reveals the abun-dance of senescent CD8+ T cells in aging humans. Aging Cell, 20:e13344, 2021(PMID:33939265)
 
246) Ucar D, et al:The chromatin accessibility signature of human immune aging stems from CD8+ T cells. J Exp Med, 214:3123-3144, 2017(PMID:28904110)
 
247) Moskowitz DM, et al:Epigenomics of human CD8 T cell differentiation and aging. Sci Immunol, 2:doi:10.1126/sciimmunol.aag0192, 2017(PMID:28439570)
 
248) Desdin-Mico G, et al:T cells with dysfunctional mitochondria induce multimorbidity and premature senescence. Science, 368:1371-1376, 2020(PMID:32439659)
 
249) Li G, et al:Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nat Med, 18:1518-1524, 2012(PMID:23023500)
 
250) Kim C, et al:Histone deficiency and accelerated replication stress in T cell aging. J Clin Invest, 131:doi:10.1172/JCI143632, 2021(PMID:34060486)
 
251) Kim C, et al:Activation of miR-21-Regulated Pathways in Immune Aging Selects against Signatures Characteristic of Memory T Cells. Cell Rep, 25:2148-2162.e5, 2018(PMID:30463012)
 
P.73 掲載の参考文献
252) McKenna RW, et al:Immunophenotypic analysis of hematogones (B-lymphocyte precur-sors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood, 98:2498-2507, 2001(PMID:11588048)
 
253) Ademokun A, et al:The ageing B cell population: composition and function. Biogeron-tology, 11:125-137, 2010(PMID:19937382)
 
254) Kyle RA, et al:Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med, 354:1362-1369, 2006(PMID:16571879)
 
255) Manoussakis MN, et al:High prevalence of anti-cardiolipin and other autoantibodies in a healthy elderly population. Clin Exp Immunol, 69:557-565, 1987(PMID:3499270)
 
256) Candore G, et al:Prevalence of organ-specific and non organ-specific autoantibodies in healthy centenarians. Mech Ageing Dev, 94:183-190, 1997(PMID:9147370)
 
257) Vadasz Z, et al:Age-related autoimmunity. BMC Med, 11:94, 2013(PMID:23556986)
 
258) Frasca D, et al:B Cell Immunosenescence. Annu Rev Cell Dev Biol, 36:551-574, 2020(PMID:33021823)
 
259) Berchtold NC, et al:Gene expression changes in the course of normal brain aging are sexually dimorphic. Proc Natl Acad Sci U S A, 105:15605-15610, 2008(PMID:18832152)
 
260) Peters MJ, et al:The transcriptional landscape of age in human peripheral blood. Nat Commun, 6:8570, 2015(PMID:26490707)
 
261) Trim WV, et al:Divergent immunometabolic changes in adipose tissue and skeletal muscle with ageing in healthy humans. J Physiol, 600:921-947, 2022(PMID:33895996)
 
262) Park SK, et al:Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants. Aging Cell, 8:484-495, 2009(PMID:19555370)
 
263) Hickson LJ, et al:Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine, 47:446-456, 2019(PMID:31542391)
 
264) Aprahamian T, et al:Ageing is associated with diminished apoptotic cell clearance in vivo. Clin Exp Immunol, 152:448-455, 2008(PMID:18422728)
 
265) Teo YV, et al:Cell-free DNA as a biomarker of aging. Aging Cell, 18:e12890, 2019(PMID:30575273)
 
266) Miller KN, et al:Cytoplasmic DNA: sources, sensing, and role in aging and disease. Cell, 184:5506-5526, 2021(PMID:34715021)
 
267) Maggio M, et al:Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci, 61:575-584, 2006(PMID:16799139)
 
268) Paolisso G, et al:Advancing age and insulin resistance: role of plasma tumor necrosis fac-tor-alpha. Am J Physiol, 275:E294-E299, 1998(PMID:9688632)
 
269) Bruunsgaard H, et al:A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci, 54:M357-M364, 1999(PMID:10462168)
 
270) Giovannini S, et al:Interleukin-6, C-reactive protein, and tumor necrosis factor-alpha as predictors of mortality in frail, community-living elderly individuals. J Am Geriatr Soc, 59:1679-1685, 2011(PMID:21883115)
 
271) Adriaensen W, et al:Interleukin-6 as a first-rated serum inflammatory marker to predict mortality and hospitalization in the oldest old: A regression and CART approach in the BELFRAIL study. Exp Gerontol, 69:53-61, 2015(PMID:26051931)
 
272) Roubenoff R, et al:Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med, 115:429-435, 2003(PMID:14563498)
 
273) Franceschi C, et al:Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev, 128:92-105, 2007(PMID:17116321)
 
274) Sato Y, et al:Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians. Nature, 599:458-464, 2021 (PMID:34325466)
 
275) Bartlett DB, et al:The age-related increase in low-grade systemic inflammation (Inflam-maging) is not driven by cytomegalovirus infection. Aging Cell, 11:912-915, 2012(PMID:22708923)
 
276) Roberts ET, et al:Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol, 172:363-371, 2010(PMID:20660122)
 
P.75 掲載の参考文献
b10) Andziak B, et al:High oxidative damage levels in the longest-living rodent, the naked mole-rat. Aging Cell, 5:463-471, 2006(PMID:17054663)
 
b11) Perez VI, et al:Protein stability and resistance to oxidative stress are determinants of lon-gevity in the longest-living rodent, the naked mole-rat. Proc Natl Acad Sci U S A, 106:3059-3064, 2009(PMID:19223593)
 
b12) De Waal EM, et al:Elevated protein carbonylation and oxidative stress do not affect pro-tein structure and function in the long-living naked-mole rat: a proteomic approach. Bio-chem Biophys Res Commun, 434:815-819, 2013(PMID:23618867)
 
b13) Kim EB, et al:Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature, 479:223-227, 2011(PMID:21993625)
 
P.76 掲載の参考文献
277) Skulachev VP, et al:Neoteny, Prolongation of Youth: From Naked Mole Rats to"Naked Apes" (Humans). Physiol Rev, 97:699-720, 2017(PMID:28202600)
 
P.77 掲載の参考文献
278) Yang J, et al:Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases. Sci Rep, 5:15145, 2015(PMID:26477495)
 
279) Rodwell GE, et al:A transcriptional profile of aging in the human kidney. PLoS Biol, 2:e427, 2004(PMID:15562319)
 
280) Chow RD, et al:The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2. Nat Commun, 12:4, 2021(PMID:33397975)
 
281) Lu T, et al:REST and stress resistance in ageing and Alzheimer's disease. Nature, 507:448-454, 2014(PMID:24670762)
 
282) Zullo JM, et al:Regulation of lifespan by neural excitation and REST. Nature, 574:359-364, 2019(PMID:31619788)
 
283) Somel M, et al:MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res, 20:1207-1218, 2010(PMID:20647238)
 
284) Somel M, et al:Transcriptional neoteny in the human brain. Proc Natl Acad Sci U S A, 106:5743-5748, 2009(PMID:19307592)
 
P.79 掲載の参考文献
285) Thompson RF, et al:Tissue-specific dysregulation of DNA methylation in aging. Aging Cell, 9:506-518, 2010(PMID:20497131)
 
286) Slieker RC, et al:Age-related DNA methylation changes are tissue-specific with ELOVL2 promoter methylation as exception. Epigenetics Chromatin, 11:25, 2018(PMID:29848354)
 
287) Wilson VL, et al:Genomic 5-methyldeoxycytidine decreases with age. J Biol Chem, 262: 9948-9951, 1987(PMID:3611071)
 
288) Unnikrishnan A, et al:Revisiting the genomic hypomethylation hypothesis of aging. Ann N Y Acad Sci, 1418:69-79, 2018(PMID:29363785)
 
289) Bollati V, et al:Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev, 130:234-239, 2009(PMID:19150625)
 
290) Christensen BC, et al:Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet, 5:e1000602, 2009(PMID:19680444)
 
291) Rakyan VK, et al:Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res, 20:434-439, 2010(PMID:20219945)
 
292) Maegawa S, et al:Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res, 20:332-340, 2010(PMID:20107151)
 
293) Teschendorff AE, et al:Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res, 20:440-446, 2010(PMID:20219944)
 
294) Takasugi M:Progressive age-dependent DNA methylation changes start before adulthood in mouse tissues. Mech Ageing Dev, 132:65-71, 2011(PMID:21184773)
 
295) Horvath S & Raj K:DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet, 19:371-384, 2018(PMID:29643443)
 
296) Horvath S:DNA methylation age of human tissues and cell types. Genome Biol, 14:R115, 2013(PMID:24138928)
 
297) Levine ME, et al:An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY), 10:573-591, 2018(PMID:29676998)
 
298) Mammalian Methylation Consortium:Universal DNA methylation age across mammalian tissues. bioRxiv, doi:10.1101/2021.01.18.426733, 2021
 
299) Bacalini MG, et al:Systemic Age-Associated DNA Hypermethylation of ELOVL2 Gene: In Vivo and In Vitro Evidences of a Cell Replication Process. J Gerontol A Biol Sci Med Sci, 72:1015-1023, 2017(PMID:27672102)
 
P.82 掲載の参考文献
300) Dexheimer TS:DNA Repair Pathways and Mechanisms.「DNA Repair of Cancer Stem Cells」(Mathews LA,et al, eds), pp19-32, Springer, 2013
 
301) Petr MA, et al:Protecting the Aging Genome. Trends Cell Biol, 30:117-132, 2020(PMID:31917080)
 
302) Yousefzadeh M, et al:DNA damage-how and why we age? Elife, 10:e62852, 2021(PMID:33512317)
 
303) Schumacher B, et al:The central role of DNA damage in the ageing process. Nature, 592:695-703, 2021(PMID:33911272)
 
P.84 掲載の参考文献
304) Robinson PS, et al:Increased somatic mutation burdens in normal human cells due to defective DNA polymerases. Nat Genet, 53:1434-1442, 2021(PMID:34594041)
 
305) Martincorena I, et al:Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science, 348:880-886, 2015(PMID:25999502)
 
306) Yokoyama A, et al:Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature, 565:312-317, 2019(PMID:30602793)
 
307) Yizhak K, et al:RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science, 364:doi:10.1126/science.aaw0726, 2019(PMID:31171663)
 
P.86 掲載の参考文献
b14) Seluanov A, et al:Hypersensitivity to contact inhibition provides a clue to cancer resis-tance of naked mole-rat. Proc Natl Acad Sci U S A, 106:19352-19357, 2009(PMID:19858485)
 
b15) Liang S, et al:Resistance to experimental tumorigenesis in cells of a long-lived mammal, the naked mole-rat (Heterocephalus glaber). Aging Cell, 9:626-635, 2010(PMID:20550519)
 
b16) Miyawaki S, et al:Tumour resistance in induced pluripotent stem cells derived from naked mole-rats. Nat Commun, 7:11471, 2016(PMID:27161380)
 

第3章 老化治療薬としての可能性が有望視される主要な物質

P.88 掲載の参考文献
308) Partridge L, et al:The quest to slow ageing through drug discovery. Nat Rev Drug Discov, 19:513-532, 2020(PMID:32467649)
 
P.89 掲載の参考文献
309) Perry HM 3rd, et al:Longitudinal changes in serum 25-hydroxyvitamin D in older people. Metabolism, 48:1028-1032, 1999(PMID:10459569)
 
310) Murad MH, et al:Clinical review: The effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab, 96:2997-3006, 2011(PMID:21795448)
 
311) Bergman GJ, et al:Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: a meta-analysis. Curr Med Res Opin, 26:1193-1201, 2010(PMID:20302551)
 
312) Bischoff-Ferrari HA, et al:Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med,169:551-561, 2009(PMID:19307517)
 
313) Melamed ML, et al:25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med, 168:1629-1637, 2008(PMID:18695076)
 
314) Rejnmark L, et al:Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials. J Clin Endocrinol Metab, 97:2670-2681, 2012(PMID:22605432)
 
315) Zhang Y, et al:Association between vitamin D supplementation and mortality: systematic review and meta-analysis. BMJ, 366:l4673, 2019(PMID:31405892)
 
316) Bouillon R, et al:The health effects of vitamin D supplementation: evidence from human studies. Nat Rev Endocrinol, 18:96-110, 2022(PMID:34815552)
 
317) Geleijnse JM, et al:Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr, 134:3100-3105, 2004(PMID:15514282)
 
318) Popa DS, et al:The Role of Vitamin K in Humans: Implication in Aging and Age-Associ-ated Diseases. Antioxidants (Basel), 10:doi:10.3390/antiox10040566, 2021(PMID:33917442)
 
319) Lees JS, et al:Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis. Heart, 105:938-945, 2019(PMID:30514729)
 
P.91 掲載の参考文献
320) Feldman HA, et al:Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab, 87:589-598, 2002(PMID:11836290)
 
321) Chu LW, et al:Bioavailable testosterone is associated with a reduced risk of amnestic mild cognitive impairment in older men. Clin Endocrinol (Oxf), 68:589-598, 2008(PMID:17973937)
 
322) Chu LW, et al:Bioavailable testosterone predicts a lower risk of Alzheimer's disease in older men. J Alzheimers Dis, 21:1335-1345, 2010(PMID:21504130)
 
323) Baumgartner RN, et al:Predictors of skeletal muscle mass in elderly men and women. Mech Ageing Dev, 107:123-136, 1999(PMID:10220041)
 
324) Wittert GA, et al:Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci, 58:618-625, 2003(PMID:12865477)
 
325) Page ST, et al:Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J Clin Endocrinol Metab, 90:1502-1510, 2005(PMID:15572415)
 
326) Khaw KT, et al:Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation, 116:2694-2701, 2007(PMID:18040028)
 
327) Haring R, et al:Low serum testosterone levels are associated with increased risk of mor-tality in a population-based cohort of men aged 20-79. Eur Heart J, 31:1494-1501, 2010(PMID:20164245)
 
328) Rosano GM, et al:Low testosterone levels are associated with coronary artery disease in male patients with angina. Int J Impot Res, 19:176-182, 2007(PMID:16943795)
 
329) Aversa A, et al:Effects of testosterone undecanoate on cardiovascular risk factors and ath-erosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome:results from a 24-month, randomized, double-blind, placebo-controlled study. J Sex Med, 7:3495-3503, 2010(PMID:20646185)
 
330) Michaud JE, et al:Testosterone and prostate cancer: an evidence-based review of patho-genesis and oncologic risk. Ther Adv Urol, 7:378-387, 2015(PMID:26622322)
 
331) Harrison DE, et al:Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell, 13:273-282, 2014(PMID:24245565)
 
332) Strong R, et al:Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, anα-glucosidase inhibitor or a Nrf2-inducer. Aging Cell, 15:872-884, 2016(PMID:27312235)
 
333) Mikkola TS, et al:Estradiol-based postmenopausal hormone therapy and risk of cardio-vascular and all-cause mortality. Menopause, 22:976-983, 2015(PMID:25803671)
 
334) Hodis HN, et al:Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med, 374:1221-1231, 2016(PMID:27028912)
 
335) Rossouw JE, et al:Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA, 288:321-333, 2002(PMID:12117397)
 
336) Orentreich N, et al:Long-term longitudinal measurements of plasma dehydroepiandros-terone sulfate in normal men. J Clin Endocrinol Metab, 75:1002-1004, 1992(PMID:1400863)
 
337) Labrie F, et al:Marked decline in serum concentrations of adrenal C19 sex steroid precur-sors and conjugated androgen metabolites during aging. J Clin Endocrinol Metab, 82:2396-2402, 1997(PMID:9253307)
 
338) Barrett-Connor E, et al:A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med, 315:1519-1524, 1986(PMID:2946952)
 
339) Shufelt C, et al:DHEA-S levels and cardiovascular disease mortality in postmenopausal women: results from the National Institutes of Health--National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE). J Clin Endocrinol Metab, 95:4985-4992, 2010(PMID:20739385)
 
340) Morley JE:Scientific overview of hormone treatment used for rejuvenation. Fertil Steril, 99:1807-1813, 2013(PMID:23726254)
 
341) Samaras N, et al:Off-label use of hormones as an antiaging strategy: a review. Clin Interv Aging, 9:1175-1186, 2014(PMID:25092967)
 
P.93 掲載の参考文献
342) Han Y, et al:Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis. Cardiovasc Diabetol, 18:96, 2019(PMID:31362743)
 
343) Wang CP, et al:Differential effects of metformin on age related comorbidities in older men with type 2 diabetes. J Diabetes Complications, 31:679-686, 2017(PMID:28190681)
 
P.94 掲載の参考文献
344) Perrone RD, et al:Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD). Kidney Int, 100:684-696, 2021(PMID:34186056)
 
345) Espinoza SE, et al:Rationale and Study Design of a Randomized Clinical Trial of Met-formin to Prevent Frailty in Older Adults With Prediabetes. J Gerontol A Biol Sci Med Sci, 75:102-109, 2020(PMID:30888034)
 
346) El-Mir MY, et al:Dimethylbiguanide inhibits cell respiration via an indirect effect tar-geted on the respiratory chain complex I. J Biol Chem, 275:223-228, 2000(PMID:10617608)
 
347) Zhang CS, et al:Metformin Activates AMPK through the Lysosomal Pathway. Cell Metab, 24:521-522, 2016(PMID:27732831)
 
348) Ma T, et al:Low-dose metformin targets the lysosomal AMPK pathway through PEN2. Nature, 603:159-165, 2022(PMID:35197629)
 
349) Wang Y, et al:Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK. Cell Rep, 29:1511-1523.e5, 2019(PMID:31693892)
 
P.95 掲載の参考文献
350) Anisimov VN, et al:Metformin slows down aging and extends life span of female SHR mice. Cell Cycle, 7:2769-2773, 2008(PMID:18728386)
 
351) Martin-Montalvo A, et al:Metformin improves healthspan and lifespan in mice. Nat Commun, 4:2192, 2013(PMID:23900241)
 
352) Zhu X, et al:Effect of Metformin on Cardiac Metabolism and Longevity in Aged Female Mice. Front Cell Dev Biol, 8:626011, 2020(PMID:33585467)
 
353) Neumann B, et al:Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells. Cell Stem Cell, 25:473-485.e8, 2019(PMID:31585093)
 
354) Wang F, et al:Myelin degeneration and diminished myelin renewal contribute to age-re-lated deficits in memory. Nat Neurosci, 23:481-486, 2020(PMID:32042174)
 
355) Zhu X, et al:Metformin improves cognition of aged mice by promoting cerebral angiogen-esis and neurogenesis. Aging (Albany NY), 12:17845-17862, 2020(PMID:32938817)
 
356) Kodali M, et al:Metformin treatment in late middle age improves cognitive function with alleviation of microglial activation and enhancement of autophagy in the hippocampus. Aging Cell, 20:e13277, 2021(PMID:33443781)
 
P.96 掲載の参考文献
357) Day EA, et al:Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss. Nat Metab, 1:1202-1208, 2019(PMID:32694673)
 
358) Coll AP, et al:GDF15 mediates the effects of metformin on body weight and energy bal-ance. Nature, 578:444-448, 2020(PMID:31875646)
 
359) Natali A, et al:Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes: A nested, case-control study. Diabetes Obes Metab, 21:412-416, 2019(PMID:30178545)
 
360) Gerstein HC, et al:Growth Differentiation Factor 15 as a Novel Biomarker for Metformin. Diabetes Care, 40:280-283, 2017(PMID:27974345)
 
361) Moon JS, et al:Growth differentiation factor 15 protects against the aging-mediated sys-temic inflammatory response in humans and mice. Aging Cell, 19:e13195, 2020(PMID:32691494)
 
362) Wang D, et al:GDF15: emerging biology and therapeutic applications for obesity and car-diometabolic disease. Nat Rev Endocrinol, 17:592-607, 2021(PMID:34381196)
 
P.97 掲載の参考文献
363) Fahy GM, et al:Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell, 18:e13028, 2019(PMID:31496122)
 
364) Kelley KW, et al:GH3 pituitary adenoma cells can reverse thymic aging in rats. Proc Natl Acad Sci U S A, 83:5663-5667, 1986(PMID:2874554)
 
365) Napolitano LA, et al:Growth hormone enhances thymic function in HIV-1-infected adults. J Clin Invest, 118:1085-1098, 2008(PMID:18292808)
 
366) Marcus R, et al:Effects of short term administration of recombinant human growth hor-mone to elderly people. J Clin Endocrinol Metab, 70:519-527, 1990(PMID:2298863)
 
367) Bartke A:Growth Hormone and Aging: Updated Review. World J Mens Health, 37:19-30, 2019(PMID:29756419)
 
P.99 掲載の参考文献
368) Wilkinson JE, et al:Rapamycin slows aging in mice. Aging Cell, 11:675-682, 2012(PMID:22587563)
 
369) Ma Y, et al:Autophagy controls mesenchymal stem cell properties and senescence during bone aging. Aging Cell, 17:e12709, 2018(PMID:29210174)
 
370) Urfer SR, et al:A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs. Geroscience, 39:117-127, 2017(PMID:28374166)
 
371) Quarles E, et al:Rapamycin persistently improves cardiac function in aged, male and female mice, even following cessation of treatment. Aging Cell, 19:e13086, 2020(PMID:31823466)
 
372) Chung CL, et al:Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial. Geroscience, 41:861-869, 2019(PMID:31761958)
 
373) Mannick JB, et al:mTOR inhibition improves immune function in the elderly. Sci Transl Med, 6:268ra179, 2014(PMID:25540326)
 
374) Mannick JB, et al:TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med, 10:doi:10.1126/scitranslmed.aaq1564, 2018(PMID:29997249)
 
P.101 掲載の参考文献
375) Karunadharma PP, et al:Subacute calorie restriction and rapamycin discordantly alter mouse liver proteome homeostasis and reverse aging effects. Aging Cell, 14:547-557, 2015(PMID:25807975)
 
376) Laberge RM, et al:MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol, 17:1049-1061, 2015(PMID:26147250)
 
377) Herranz N, et al:mTOR regulates MAPKAPK2 translation to control the senescence-asso-ciated secretory phenotype. Nat Cell Biol, 17:1205-1217, 2015(PMID:26280535)
 
378) Schreiber KH, et al:A novel rapamycin analog is highly selective for mTORC1 in vivo. Nat Commun, 10:3194, 2019(PMID:31324799)
 
379) Zhang Y, et al:The Role of Rapamycin in Healthspan Extension via the Delay of Organ Aging. Ageing Res Rev, 70:101376, 2021(PMID:34089901)
 
P.103 掲載の参考文献
b17) Tian X, et al:High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature, 499:346-349, 2013(PMID:23783513)
 
b18) Takasugi M, et al:Naked mole-rat very-high-molecular-mass hyaluronan exhibits supe-rior cytoprotective properties. Nat Commun, 11:2376, 2020(PMID:32398747)
 
b19) Zhang Z, et al:Naked Mole-Rat Hyaluronan Synthase 2 Promotes Longevity and Enhances Healthspan in Mice. Available at SSRN:https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4185135
 
P.104 掲載の参考文献
380) Frederick DW, et al:Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle. Cell Metab, 24:269-282, 2016(PMID:27508874)
 
381) Liu L, et al:Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. Cell Metab, 27:1067-1080.e5, 2018(PMID:29685734)
 
382) Sauve AA & Schramm VL:Sir2 regulation by nicotinamide results from switching between base exchange and deacetylation chemistry. Biochemistry, 42:9249-9256, 2003(PMID:12899610)
 
383) Nacarelli T, et al:NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol, 21:397-407, 2019(PMID:30778219)
 
384) Dai H, et al:Sirtuin activators and inhibitors: Promises, achievements, and challenges. Pharmacol Ther, 188:140-154, 2018(PMID:29577959)
 
P.106 掲載の参考文献
385) Zhang H, et al:NAD + repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, 352:1436-1443, 2016(PMID:27127236)
 
386) Sun X, et al:Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells. Nat Commun, 12:2665, 2021(PMID:33976125)
 
387) Harrison DE, et al:17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging Cell, 20:e13328, 2021(PMID:33788371)
 
388) Mitchell SJ, et al:Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice. Cell Metab, 27:667-676.e4, 2018(PMID:29514072)
 
389) Mills KF, et al:Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab, 24:795-806, 2016(PMID:28068222)
 
390) Gomes AP, et al:Declining NAD(+) induces a pseudohypoxic state disrupting nucle-ar-mitochondrial communication during aging. Cell, 155:1624-1638, 2013(PMID:24360282)
 
391) Covarrubias AJ, et al:NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol, 22:119-141, 2021(PMID:33353981)
 
392) de Picciotto NE, et al:Nicotinamide mononucleotide supplementation reverses vasculardysfunction and oxidative stress with aging in mice. Aging Cell, 15:522-530, 2016(PMID:26970090)
 
393) Tarantini S, et al:Nicotinamide mononucleotide (NMN) supplementation rescues cere-bromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biol, 24:101192, 2019(PMID:31015147)
 
P.108 掲載の参考文献
394) Yoshino M, et al:Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 372:1224-1229, 2021(PMID:33888596)
 
395) Martens CR, et al:Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun, 9:1286, 2018(PMID:29599478)
 
396) Dollerup OL, et al:A randomized placebo-controlled clinical trial of nicotinamide ribo-side in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr, 108:343-353, 2018(PMID:29992272)
 
397) Dollerup OL, et al:Effects of Nicotinamide Riboside on Endocrine Pancreatic Function and Incretin Hormones in Nondiabetic Men With Obesity. J Clin Endocrinol Metab, 104:5703-5714, 2019(PMID:31390002)
 
398) Giroud-Gerbetant J, et al:A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor. Mol Metab, 30:192-202, 2019(PMID:31767171)
 
399) Bai P, et al:PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activa-tion. Cell Metab, 13:461-468, 2011(PMID:21459330)
 
400) Scheibye-Knudsen M, et al:A high-fat diet and NAD(+) activate Sirt1 to rescue prema-ture aging in cockayne syndrome. Cell Metab, 20:840-855, 2014(PMID:25440059)
 
401) Camacho-Pereira J, et al:CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab, 23:1127-1139, 2016(PMID:27304511)
 
402) Covarrubias AJ, et al:Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. Nat Metab, 2:1265-1283, 2020(PMID:33199924)
 
403) Tarrago MG, et al:A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Meta-bolic Dysfunction by Reversing Tissue NAD+ Decline. Cell Metab, 27:1081-1095.e10, 2018(PMID:29719225)
 
404) Peclat TR, et al:CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging. Aging Cell, 21:e13589, 2022(PMID:35263032)
 
P.110 掲載の参考文献
405) Zhu Y, et al:The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell, 14:644-658, 2015(PMID:25754370)
 
406) 高杉征樹,大谷直子:senolytic drug 開発の動向と展望.実験医学,40:407-412,2022
Medical*Online
407) Xu Q, et al:The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice. Nat Metab, 3:1706-1726, 2021(PMID:34873338)
 
408) Zhu Y, et al:New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463. Aging (Albany NY), 9:955-963, 2017(PMID:28273655)
 
409) Grosse L, et al:Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan. Cell Metab, 32:87-99.e6, 2020(PMID:32485135)
 
P.112 掲載の参考文献
410) Wilson WH, et al:Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacody-namics, and antitumour activity. Lancet Oncol, 11:1149-1159, 2010(PMID:21094089)
 
411) Triana-Martinez F, et al:Identification and characterization of Cardiac Glycosides as senolytic compounds. Nat Commun, 10:4731, 2019(PMID:31636264)
 
412) Wakita M, et al:A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells. Nat Commun, 11:1935, 2020(PMID:32321921)
 
413) Tahir S, et al:A CD153+CD4+ T follicular cell population with cell-senescence features plays a crucial role in lupus pathogenesis via osteopontin production. J Immunol, 194:5725-5735, 2015(PMID:25972477)
 
414) Yoshida S, et al:The CD153 vaccine is a senotherapeutic option for preventing the accu-mulation of senescent T cells in mice. Nat Commun, 11:2482, 2020(PMID:32424156)
 
415) Suda M, et al:Senolytic vaccination improves normal and pathological age-related pheno-types and increases lifespan in progeroid mice. Nature Aging, 1:1117-1126, 2021
 
416) Amor C, et al:Senolytic CAR T cells reverse senescence-associated pathologies. Nature, 583:127-132, 2020(PMID:32555459)
 
417) Wang T, et al:Blocking PD-L1-PD-1 improves senescence surveillance and ageing phe-notypes. Nature, doi:10.1038/s41586-022-05388-4, 2022(PMID:36323784)
 
418) Gonzalez-Gualda E, et al:Galacto-conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity. Aging Cell, 19:e13142, 2020(PMID:32233024)
 
419) Wissler Gerdes EO, et al:Strategies for late phase preclinical and early clinical trials of senolytics. Mech Ageing Dev, 200:111591, 2021(PMID:34699859)
 
P.115 掲載の参考文献
420) Takahashi K & Yamanaka S:Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126:663-676, 2006(PMID:16904174)
 
421) Ocampo A, et al:In Vivo Amelioration of Age-Associated Hallmarks by Partial Repro-gramming. Cell, 167:1719-1733.e12, 2016(PMID:27984723)
 
422) Chen Y, et al:Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice. Science, 373:1537-1540, 2021(PMID:34554778)
 
423) Lu Y, et al:Reprogramming to recover youthful epigenetic information and restore vision. Nature, 588:124-129, 2020(PMID:33268865)
 
424) Gill D, et al:Multi-omic rejuvenation of human cells by maturation phase transient repro-gramming. Elife, 11:e71624, 2022(PMID:35390271)
 
425) Eisenstein M:Rejuvenation by controlled reprogramming is the latest gambit in anti-aging. Nat Biotechnol, 40:144-146, 2022(PMID:35046614)
 
P.117 掲載の参考文献
426) Nadon NL, et al:NIA Interventions Testing Program: Investigating Putative Aging Inter-vention Agents in a Genetically Heterogeneous Mouse Model. EBioMedicine, 21:3-4, 2017(PMID:27923560)
 
427) Harrison DE, et al:Acarbose improves health and lifespan in aging HET3 mice. Aging Cell, 18:e12898, 2019(PMID:30688027)
 
428) Miller RA, et al:Glycine supplementation extends lifespan of male and female mice. Aging Cell, 18:e12953, 2019(PMID:30916479)
 
429) Strong R, et al:Nordihydroguaiaretic acid and aspirin increase lifespan of genetically het-erogeneous male mice. Aging Cell, 7:641-650, 2008(PMID:18631321)
 
430) McNeil JJ, et al:Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. N Engl J Med, 379:1519-1528, 2018(PMID:30221595)
 
431) McNeil JJ, et al:Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. N Engl J Med, 379:1509-1518, 2018(PMID:30221597)
 

書評

最近チェックした商品履歴

Loading...