Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes

Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Volumn 71, Issue 11, 2016, Pages 1415-1423

  Justice, Jamie ^a   Miller, Jordan D ^b,c   Newman, John C ^d   Hashmi, Shahrukh K ^c   Halter, Jeffrey ^e   Austad, Steve N ^f   Barzilai, Nir ^g,h   Kirkland, James L ^b,c  

^a WAKE FOREST SCHOOL OF MEDICINE   (United States)

^b Department of Surgery ^*  (United States)

^c MAYO CLINIC   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF MICHIGAN   (United States)

^f UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^g Division of Endocrinology Department of Pediatrics   (United States)

^h ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Aging; Clinical trials; Geroscience Network

Indexed keywords

BIOLOGICAL MARKER;

AGED; AGING; ANIMAL; CHRONIC DISEASE; CLINICAL TRIAL (TOPIC); DISEASE COURSE; DISEASE MODEL; HUMAN; LONGEVITY; MEDICAL RESEARCH; METHODOLOGY; ORGANIZATION; PATHOLOGY;

AGED; AGING; ANIMALS; BIOMARKERS; BIOMEDICAL RESEARCH; CHRONIC DISEASE; CLINICAL TRIALS AS TOPIC; CONGRESSES AS TOPIC; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; HUMANS; LONGEVITY; RESEARCH DESIGN;

EID: 84994418099     PISSN: 10795006     EISSN: 1758535X     Source Type: Journal    
DOI: 10.1093/gerona/glw126     Document Type: Article

References (55)

1. Harrison DE, Strong R, Allison DB, et al. Acarbose, 17-alpha-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell. 2014;13:273-282. doi:10.1111/acel.12170
2. Wilkinson JE, Burmeister L, Brooks SV, et al. Rapamycin slows aging in mice. Aging Cell. 2012;11:675-682. doi:10.1111/j.1474-9726.2012.00832.x
3. Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392-395. doi:10.1038/nature08221
4. Martin-Montalvo A, Mercken EM, Mitchell SJ, et al. Metformin improves health span and lifespan in mice. Nat Commun. 2013;4:2192. doi:10.1038/ncomms3192
5. Roos CM, Zhang B, Palmer AK, et al. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell. [published online ahead of print February 10,2016]. doi:10.1111/acel.12458
6. Xu M, Tchkonia T, Ding H, et al. JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proc Natl Acad Sci USA. 2015;112:E6301-6310. doi:10.1073/pnas.1515386112
7. Xu M, Palmer AK, Ding H, et al. Targeting senescent cells enhances adipogenesis and metabolic function in old age. Elife. 2015;4:e12997. doi:10.7554/eLife.12997
8. Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14:644-658. doi:10.1111/acel.12344
9. Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, et al. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell. 2016;15:428-435. doi:10.1111/acel.12445
10. Bjedov I, Partridge L. A longer and healthier life with TOR down-regulation: genetics and drugs. Biochem Soc Trans. 2011;39:460-465. doi:10.1042/BST0390460
11. Stout MB, Steyn FJ, Jurczak MJ, et al. 17-Estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. J Gerontol A Biol Sci Med Sci. 2016. doi:10.1093/gerona/ glv309
12. Schmidt B. Proof of principle studies. Epilepsy Res. 2006;68:48-52. doi:10.1016/j.eplepsyres.2005.09.019
13. Kennedy BK, Berger SL, Brunet A, et al. Geroscience: linking aging to chronic disease. Cell. 2014;159:709-713. doi:10.1016/j.cell.2014.10.039
14. Seals DR, Melov S. Translational geroscience: emphasizing function to achieve optimal longevity. Aging. 2014;6:718-730. doi:10.18632/ aging.100694
15. Burch JB, Augustine AD, Frieden LA, et al. Advances in geroscience: impact on healthspan and chronic disease. J Gerontol A Biol Sci Med Sci. 2014;69(suppl 1):S1-S3. doi:10.1093/gerona/glu041
16. Corr PB, Williams DA. Pathway from idea to regulatory approval: examples for drug development. In: Lo E, Field MJ, eds. Institute of Medicine (US) Committee on Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: National Academies Press; 2009, 375-383
17. Hazzard WR, Halter JB. Hazzard's Geriatric Medicine and Gerontology. 6th ed. New York, NY: McGraw-Hill Medical Publication Division; 2009
18. Kim YC, Guan KL. mTOR: a pharmacologic target for autophagy regulation. J Clin Invest. 2015;125:25-32. doi:10.1172/JCI73939
19. Luo D, Ren H, Li T, Lian K, Lin D. Rapamycin reduces severity of senile osteoporosis by activating osteocyte autophagy. Osteoporos Int. 2016;27:1093-1101. doi:10.1007/s00198-015-3325-5
20. Inouye SK, Studenski S, Tinetti ME, Kuchel GA. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc. 2007;55:780-791. doi:10.1111/j.1532-5415.2007.01156.x
21. Hshieh TT, Yue J, Oh E, et al. Effectiveness of multicomponent nonpharmacological delirium interventions: a meta-analysis. JAMA Intern Med. 2015;175:512-520. doi:10.1001/jamainternmed.2014.7779
22. Kane AE, Hilmer SN, Boyer D, et al. Impact of longevity interventions on a validated mouse clinical frailty index. J Gerontol A Biol Sci Med Sci. 2016;71:333-339. doi:10.1093/gerona/glu315
23. Brothers TD, Rockwood K. Biologic aging, frailty, and age-related disease in chronic HIV infection. Curr Opin HIV AIDS. 2014;9:412-418. doi:10.1097/COH.0000000000000070
24. Williams BA, Goodwin JS, Baillargeon J, Ahalt C, Walter LC. Addressing the aging crisis in U.S. criminal justice health care. J Am Geriatr Soc. 2012;60:1150-1156. doi:10.1111/j.1532-5415.2012.03962.x
25. Sanoff HK, Deal AM, Krishnamurthy J, et al. Effect of cytotoxic chemotherapy on markers of molecular age in patients with breast cancer. J Natl Cancer Inst. 2014;106:dju057. doi:10.1093/jnci/dju057
26. Cimino T, Steinman MA, Mitchell SL, et al. The course of functional impairment in older homeless adults: disabled on the street. JAMA Intern Med. 2015;175:1237-1239. doi:10.1001/jamainternmed.2015.1562
27. Roberts HC, Denison HJ, Martin HJ, et al. A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing. 2011;40:423-429. doi:10.1093/ageing/ afr051
28. Romanick M, Thompson LV, Brown-Borg HM. Murine models of atrophy, cachexia, and sarcopenia in skeletal muscle. Biochim Biophys Acta. 2013;1832:1410-1420. doi:10.1016/j.bbadis.2013.03.011
29. Nilsson J, Thomas AJ, O'Brien JT, Gallagher P. White matter and cognitive decline in aging: a focus on processing speed and variability. J Int Neuropsychol Soc. 2014;20:262-267. doi:10.1017/S1355617713001458
30. Troncale JA. The aging process. Physiologic changes and pharmacologic implications. Postgrad Med. 1996;99:111-114, 120-122
31. Gill TM, Allore HG, Holford TR, Guo Z. Hospitalization, restricted activity, and the development of disability among older persons. JAMA. 2004;292:2115-2124. doi:10.1001/jama.292.17.2115
32. Guralnik JM, Alecxih L, Branch LG, Wiener JM. Medical and long-term care costs when older persons become more dependent. Am J Public Health. 2002;92:1244-1245. doi:10.2105/ajph.92.8.1244
33. Debes C, Aissou M, Beaussier M. Prehabilitation. Preparing patients for surgery to improve functional recovery and reduce postoperative morbidity. Ann Fr Anesth Reanim. 2014;33:33-40. doi:10.1016/j.annfar.2013.12.012
34. Demark-Wahnefried W, Clipp EC, Morey MC, et al. Lifestyle intervention development study to improve physical function in older adults with cancer: outcomes from Project LEAD. J Clin Oncol. 2006;24:3465-3473. doi:10.1200/JCO.2006.05.7224
35. Meynet O, Ricci JE. Caloric restriction and cancer: molecular mechanisms and clinical implications. Trends Mol Med. 2014;20:419-427. doi:10.1016/j.molmed.2014.05.001
36. Avery GJ 2nd, Ley SJ, Hill JD, Hershon JJ, Dick SE. Cardiac surgery in the octogenarian: evaluation of risk, cost, and outcome. Ann Thorac Surg. 2001;71:591-596. doi:10.1016/s0003-4975(00)02163-9
37. Craver JM, Puskas JD, Weintraub WW, et al. 601 octogenarians undergoing cardiac surgery: outcome and comparison with younger age groups. Ann Thorac Surg. 1999;67:1104-1110. doi:10.1016/s0003-4975(99)00154-x
38. Siriett V, Salerno MS, Berry C, et al. Antagonism of myostatin enhances muscle regeneration during sarcopenia. Mol Ther. 2007;15:1463-1470. doi:10.1038/sj.mt.6300182
39. Kortebein P, Symons TB, Ferrando A, et al. Functional impact of 10 days of bed rest in healthy older adults. J Gerontol A Biol Sci Med Sci. 2008;63:1076-1081. doi:10.1093/gerona/63.10.1076
40. Longo VD, Antebi A, Bartke A, et al. Interventions to slow aging in humans: are we ready? Aging Cell. 2015;14:497-510. doi:10.1111/acel.12338
41. Seals DR, Justice JN, LaRocca TJ. Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J Physiol. 2016;594:2001-2024. doi:10.1113/jphysiol.2014.282665
42. Newman JC, Milman S, Hashmi S, et al. Strategies and challenges in clinical trials targeting human aging. J Gerontol A Biol Sci Med Sci. 2016;71: 1424-1434. doi:10.1093/gerona/glw149
43. Huffman DM, Justice JN, Stout MB, Kirkland JL, Barzilai N, Austad SN. Evaluating healthspan in pre-clinical models of aging and disease: guidelines, challenges and opportunities for geroscience. J Gerontol A Biol Sci Med Sci. 2016;71:1395-1406. doi:10.1093/gerona/glw106
44. Demaria M, Ohtani N, Youssef SA, et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell. 2014;31:722-733. doi:10.1016/j.devcel.2014.11.012
45. Bodine SC, Stitt TN, Gonzalez M, et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol. 2001;3:1014-1019. doi:10.1038/ncb1101-1014
46. Cesari M, Vellas B, Hsu FC, et al. A physical activity intervention to treat the frailty syndrome in older persons-results from the LIFE-P study. J Gerontol A Biol Sci Med Sci. 2015;70:216-222. doi:10.1093/gerona/glu099
47. Clark AM, Hartling L, Vandermeer B, McAlister FA. Meta-analysis: secondary prevention programs for patients with coronary artery disease. Ann Intern Med. 2005;143:659-672
48. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403. doi:10.1056/NEJMoa012512
49. Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385:2255-2263. doi:10.1016/S0140-6736(15)60461-5
50. Hobin JA, Deschamps AM, Bockman R, et al. Engaging basic scientists in translational research: identifying opportunities, overcoming obstacles. J Transl Med. 2012;10:72. doi:10.1186/1479-5876-10-72
51. Simon R. Translational research in oncology: key bottlenecks and new paradigms. Expert Rev Mol Med. 2010;12:e32. doi:10.1017/ S1462399410001638
52. Clinical Research Study Investigator's Toolbox. https://www.nia.nih.gov/ research/dgcg/clinical-research-study-investigators-toolbox. Accessed June 30, 2016
53. Gershon RC, Wagster MV, Hendrie HC, Fox NA, Cook KF, Nowinski CJ. NIH toolbox for assessment of neurological and behavioral function. Neurology. 2013;80:S2-S6. doi:10.1212/ WNL.0b013e3182872e5f
54. Riegman PH, Dinjens WN, Oosterhuis JW. Biobanking for interdisciplinary clinical research. Pathobiology. 2007;74:239-244. doi:10.1159/000104451
55. Goldman DP, Cutler D, Rowe JW, et al. Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Affairs. 2013;32:1698-1705. doi:10.1377/ hlthaff.2013.0052