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Aging and disease    2018, Vol. 9 Issue (6) : 1165-1184     DOI: 10.14336/AD.2018.1026
Review |
Emerging Anti-Aging Strategies - Scientific Basis and Efficacy
Ashok K. Shetty1,2,*, Maheedhar Kodali1,2, Raghavendra Upadhya1,2, Leelavathi N. Madhu1
1Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center College of Medicine, College Station, Texas 77843, USA
2Olin E. Teague Veterans’ Medical Center, Central Texas Veterans Health Care System, Temple, Texas 76504, USA
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The prevalence of age-related diseases is in an upward trend due to increased life expectancy in humans. Age-related conditions are among the leading causes of morbidity and death worldwide currently. Therefore, there is an urgent need to find apt interventions that slow down aging and reduce or postpone the incidence of debilitating age-related diseases. This review discusses the efficacy of emerging anti-aging approaches for maintaining better health in old age. There are many anti-aging strategies in development, which include procedures such as augmentation of autophagy, elimination of senescent cells, transfusion of plasma from young blood, intermittent fasting, enhancement of adult neurogenesis, physical exercise, antioxidant intake, and stem cell therapy. Multiple pre-clinical studies suggest that administration of autophagy enhancers, senolytic drugs, plasma from young blood, drugs that enhance neurogenesis and BDNF are promising approaches to sustain normal health during aging and also to postpone age-related neurodegenerative diseases such as Alzheimer’s disease. Stem cell therapy has also shown promise for improving regeneration and function of the aged or Alzheimer’s disease brain. Several of these approaches are awaiting critical appraisal in clinical trials to determine their long-term efficacy and possible adverse effects. On the other hand, procedures such as intermittent fasting, physical exercise, intake of antioxidants such as resveratrol and curcumin have shown considerable promise for improving function in aging, some of which are ready for large-scale clinical trials, as they are non-invasive, and seem to have minimal side effects. In summary, several approaches are at the forefront of becoming mainstream therapies for combating aging and postponing age-related diseases in the coming years.

Keywords Aging      antioxidants      astragalus      autophagy      curcumin      intermittent fasting      neurogenesis      plasma transfusion      physical exercise      resveratrol      senescent cells      senolytics      stem cells      stem cell therapy      telomeres     
Corresponding Authors: Shetty Ashok K.   
About author: These authors contributed equally to this work
Just Accepted Date: 21 November 2018   Issue Date: 08 December 2018
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Shetty Ashok K.
Kodali Maheedhar
Upadhya Raghavendra
Madhu Leelavathi N.
Cite this article:   
Shetty Ashok K.,Kodali Maheedhar,Upadhya Raghavendra, et al. Emerging Anti-Aging Strategies - Scientific Basis and Efficacy[J]. Aging and disease, 2018, 9(6): 1165-1184.
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DrugMode of actionReferences
RapamycinInhibits mTORC1 activity[202 - 204]
MSL (4-(4-fluorophenyl) sulfonyl-5-methylthio-2-phenyloxazole)Increases LC3-I to LC3-II conversion without mTOR inhibition[205, 206]
MetforminInhibits mTOR signaling and protein synthesis, activates adenosine monophosphate-activated protein kinase (AMPK)[202, 207, 208]
ResveratrolInhibits mTOR through ATP competition, promotes LC3II and beclin-1 expression[202, 209, 210]
PerifosineInhibits Akt and mTOR axis components[211]
RSVA314 and RSVA405 (Structural similarities of Resveratrol)Activates AMPK to inhibit mTOR and promote autophagy to increase Aβ degradation[212]
PREP inhibitor (KYP-2047)Targets beclin-1 and increases LC3BII and clears α-synuclein[19, 213]
BRD5631Autophagy through mTOR-independent pathway, NPC1, IL-1β Suppression[214]
PP242ATP-competitive mTOR (mTORC1 and mTORC2) inhibition[215, 216]
Torin1ATP-competitive mTOR (mTORC1 and mTORC2) inhibition[217, 218]
PI103Dual ATP-competitive mTOR (mTORC1 and mTORC2) and selective PI3KC1a inhibitor[219]
Xestospongin BInhibits IP3-mediated Ca2+ signaling, Inhibits Beclin-1 interaction with IP3R-Bcl-2 complex[220, 221]
EverolimusInhibits mTOR[222, 223]
SpermidineInhibits caspase 3-mediated Beclin 1 cleavage, Inhibits acetyltransferase EP300[224, 225]
RottlerinIncreased LC3-II[226, 227]
NiclosamideInhibits mTORC1 pathway[228, 229]
Pifithrin-αp53 inhibitor[230]
Valproic acidSuppresses Akt/mTOR pathway, Inhibits Oxidative stress[231, 232]
IR-58Inhibits mitochondrial membrane 44 (TIM44)-superoxide dismutase 2 (SOD2) pathway[233]
PrazosinIncreases p-p53 and p-AMPK and decreases Akt/mTOR[234]
VerapamilBlocks calcium channels[235, 236]
Table 1  Autophagy Enhancers
DrugMode of actionReferences
NavitoclaxTargeting Bcl-2 family[237]
FisetinTargeting Bcl-2 family, regulation of PI3K/AKT/NF-κβ to promote caspase-3 and inactivates ERK1/2[238-240]
QuercetinTargeting PI3K, Induction of HIF-1α[241, 242]
PiperlongumineInhibits Akt/mTOR signaling, depletion of the androgen receptor[243-245]
PanobinostatDecreases Bcl-xL expression and increases acetylation of Histone 3[246]
GeldanamycinInhibits HSP90[247]
DasatinibInteracts with P53 and inhibits PAI-2[241]
A1331852Inhibits Bcl-xL[239]
A1155463Inhibits Bcl-xL[239]
Table 2  Senolytic Drugs.
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