Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Vyshnavy Balendra
 -- 1969 2022-11-07 18:03:14 |
2 format correct
Conner Chen
Meta information modification 1969 2022-11-08 10:19:38 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Mishra, S.K.;  Balendra, V.;  Esposto, J.;  Obaid, A.A.;  Maccioni, R.B.;  Jha, N.K.;  Perry, G.;  Moustafa, M.;  Al-Shehri, M.;  Singh, M.P.; et al. Therapeutic Antiaging Strategies. Encyclopedia. Available online: https://encyclopedia.pub/entry/33373 (accessed on 27 July 2024).
Mishra SK,  Balendra V,  Esposto J,  Obaid AA,  Maccioni RB,  Jha NK, et al. Therapeutic Antiaging Strategies. Encyclopedia. Available at: https://encyclopedia.pub/entry/33373. Accessed July 27, 2024.
Mishra, Shailendra Kumar, Vyshnavy Balendra, Josephine Esposto, Ahmad A. Obaid, Ricardo B. Maccioni, Niraj Kumar Jha, George Perry, Mahmoud Moustafa, Mohammed Al-Shehri, Mahendra P. Singh, et al. "Therapeutic Antiaging Strategies" Encyclopedia, https://encyclopedia.pub/entry/33373 (accessed July 27, 2024).
Mishra, S.K.,  Balendra, V.,  Esposto, J.,  Obaid, A.A.,  Maccioni, R.B.,  Jha, N.K.,  Perry, G.,  Moustafa, M.,  Al-Shehri, M.,  Singh, M.P.,  Khan, A.A.,  Vamanu, E., & Singh, S.K. (2022, November 07). Therapeutic Antiaging Strategies. In Encyclopedia. https://encyclopedia.pub/entry/33373
Mishra, Shailendra Kumar, et al. "Therapeutic Antiaging Strategies." Encyclopedia. Web. 07 November, 2022.
Therapeutic Antiaging Strategies
Edit
This entry is adapted from the peer-reviewed paper 10.3390/biomedicines10102515

Aging constitutes progressive physiological changes in an organism. These changes alter the normal biological functions, such as the ability to manage metabolic stress, and eventually lead to cellular senescence. Scientific achievements have been focused on producing effective antiaging therapeutics that have dramatically improved human life expectancy. Many studies on animal models looking at genetics and dietary and pharmacological interventions have shown an enhanced lifespan. Other studies have examined antiaging strategies, such as enhancement of autophagy, elimination of senescent cells, transfusion of young blood, intermittent fasting, stem cell therapy, physical exercise, adult neurogenesis boost, and antioxidant and herbal intakes.

aging hallmarks risk factors therapeutic agent

1. Anti-Inflammatory Drugs Used as an Antiaging Approach

Chronic inflammation is one of the major contributors to age-associated diseases and aging and disrupts the normal functioning of tissues [1][2][3]. Increased activity of proinflammatory pathways accompanies inflammation with age [4][5]. Serum concentrations of proinflammatory cytokines (IL-1, IL-2, IL-6, IL-8, IL-12, IL-15, IL-17, IL-18, IL-22, IL-23, tumor necrosis factor-α, and interferon-γ) are significantly increased in normal process aging compared with younger individuals in a normal stage [6][7][8]. A chronic proinflammatory status is a pervasive feature of aging, and increased systemic inflammation is closely associated with aging and age-related diseases [9][10]. The term “inflammaging” is used to describe aging induced by chronic and persistent inflammation. Anti-inflammatory agents block certain substances in the body that cause inflammation, and various studies have shown that anti-inflammatory agents are linked to antiaging [11]. The most important drivers of age-dependent inflammation are derived at the cellular and molecular levels. In a cell, the proinflammatory senescence-associated secretory phenotype (SASP) is associated with cellular senescence that is triggered by agents such as radiation and viruses and by continuous exposure to cellular debris [12] and cellular senescence [13]. In a molecule, ROS (reactive oxygen species) and other agents can trigger inflammatory DNA damage responses that affect DNA and telomeres [14] and activate the inflammasomes and NF-kB pathway [15]. Inhibition of the inflammatory processes by genetic and pharmacological intervention is considered an effective and verified antiaging strategy [16]. Nonsteroidal anti-inflammatory drugs (NSAIDs) not only prevent certain age-associated features but also increase the lifespan in various model organisms, such as yeasts [17], nematodes [18], mice [19][20], and flies [17]; however, their effectiveness for neurodegenerative disorders (Alzheimer’s disease and Huntington’s disease [21]) is not clear, and there is a search for anti-inflammatory bioactive compounds [22][23][24][25][26]. Anti-inflammatory drugs might be considered to have great potential for extending the lifespan. In some studies, spermidine (polyamines) and their action on the expression of pro- and anti-inflammatory cytokines can directly reduce inflammation and indirectly alter inflammation and cell growth by the action of autophagy [27]. Spermidine has been reported to slow down aging due to its antiaging effects [28]. Aspirin, a potent anti-inflammatory and antioxidant compound, may affect oxidant production and cytokine responses and block glycoxidation reactions that protect against oxidative stress, as well as extend the lifespan of Caenorhabditis elegans and mice [29][30][31]. Ibuprofen (NSAID) has been shown to reduce the risk of age-related pathologies and increase the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster [32][33]. A novel NSAID, M2000, could modify oxidative stress pathways by lowering the expression levels of the SOD2, GST, iNOS, and MPO genes and reduce the risk of inflammatory diseases through its immunosuppressive effects, with no adverse side effects on the enzymatic and nonenzymatic determinants [34]. This can be recommended as an antiaging drug. MAAs (mycosporine-like amino acids), such as M2G (mycosporine-2-glycine), exhibit antioxidant, anti-inflammatory, anti-protein-glycation, and collagenase inhibition activities and show the ability to protect DNA against UV damage [35][36]. Many nutraceuticals (apigenin, quercetin, kaempferol, naringenin, catechins, epigallocatechin, genistein, cyanidin, resveratrol, etc.) and functional foods possess antioxidant activity that might play an important role in delaying aging and be effective in various human neurodegenerative diseases [25][37][38][39][40].

2. Antioxidant Activity

Phytochemicals such as phenolic acids and flavonoids have antioxidant activity, which acts by scavenging free radicals and increasing the levels of antioxidant enzymes in plasma [41]. The function of a primary antioxidant enzyme is to protect organisms from the damaging effects of superoxide radicals, which are quickened by their dismutation into hydrogen peroxide and oxygen [42]. Several studies have confirmed that quercetin is a strong antioxidant that accumulates in nematodes and displays reactive oxygen species (ROS) scavenging activity and has been demonstrated to have a positive effect on longevity and stress resistance in various animal models [43][44][45][46]. Many studies have demonstrated that NSAIDs have antioxidant activity that is mediated by free radical scavenging and antioxidant enzyme activation [47]. The antioxidant activity of NSAIDs has been witnessed in membranes, cells, and at the organismal level [47][48][49].

3. Telomere Reactivation

Telomeres are conserved microsatellite repeats TTAGGG that protect the ends of chromosomes from DNA breakage and prevent DNA end-joining, recombination, and DNA repair [50]. DNA polymerases are incapable of fully replicating the linear chromosomes owing to end replication in somatic cells, and telomeres become gradually shortened after each cell division [51]. This shortening of telomeres is usually fulfilled by the telomerase enzyme, but most somatic cells and adult stem cells do not express enough telomerase to compensate for the telomere length that leads to entering ‘replicative senescence’, which might be followed by cell death [52][53][54]. Telomere shortening occurs during normal aging and is an important biomarker of aging and longevity that is influenced by several factors, such as genetics, epigenetics, and environments [55][56][57][58]. It is also associated with many age-related diseases, such as osteoarthritis, atherosclerosis, coronary heart disease, and atrial fibrillation [59][60][61]. Several studies have reported that aging can be inhibited by the overexpression of telomerase; however, it can enhance tumorigenesis [62][63][64]. A telomerase activator, telomerase expression activator, and telomerase gene therapy have been developed as telomerase-based antiaging strategies in recent years. TA-65 is an extract of a Chinese plant (Astragalus membranaceus), a telomerase activator that can restore telomere length without cancer occurrence and improve age-related indicators, including glucose tolerance, bone health, and skin quality [65]. Additionally, some studies found that TERT transcription activator and sex hormones are directly involved in activating telomerase, which rescued telomere shortening and enhanced the lifespan [66][67]. Evidence has suggested that the reactivation of telomerase expression by using a gene therapy approach is the best example of the lifespan extension of mice and delay aging without cancer occurrence [68]. A recent study has found that Metadichol, a telomerase activator, is used to overcome organ failure by enriching cells with telomerase and is a safer alternative [69]. Another study explained that natural compounds such as 08AGTLF (Centella asiatica), Nutrient 4 (Astragalus), TA-65 (Astragalus membranaceus), OA (oleanolic acid), and MA (maslinic acid); and Nutrients 1, 2, and 3 have telomerase activation, and among all, 08AGTLF has the greatest potential to activate telomerase [70]. The impact of telomeric length on humans has been evidenced by the fact that the expression of telomerase in normal cells may extend a healthy lifespan; however, inhibition of telomerase in cancer cells may be a viable target for anticancer therapeutics [71].

4. Antiaging Approaches Using Epigenetic Drugs

The effects of chromatin on aging are probably complex and bidirectional. Chromatin remodeling appears to counter aging and age-associated diseases and extend organismal lifespan [72]. Chromatin is intensely altered during aging owing to the decreased level of histone proteins and adequate changes in histone modification that were found in recent studies in budding yeast and human fibroblast cells [73]. Elevating histone expression, reducing H4 K16 acetylation, reducing H3 N-terminal acetylation, inactivating the HDAC Rpd3, and inactivating the H3K4 methylase might be capable of extending lifespan or reverting the aged phenotype to a more youthful state of chromatin [74]. These epigenetic factors are influenced by diet, lifestyle and exogenous stress, which raises the possibility of enhancing age-related cellular dysfunction [75][76]. Several studies revealed age-associated changes in DNA methylation patterns leading to a global reduction in DNA methylation [77] (Figure 1); site-specific hypermethylation, specifically at CpG islands and polycomb target sites [78]; site-specific hypomethylation specifically at gene-poor regions, tissue-specific promoters, and polycomb protein regions; and hypermethylation in different tissues but hypomethylation, to be more tissue specific [79][80]. These changes accumulate gradually; such changes are indicative of the aging process and strongly associated with epigenetic changes such as replicative senescence [81]. Diet, lifestyle, environmental interventions, and inhibitors of epigenetic enzymes have proven to be effective in promoting longevity, as seen in various experiments [82]. Natural substances such as spermidine and resveratrol have been found to lead to deacetylation of chromatin, indicating that it has the potential to extend the lifespan in humans [83]. Many studies report that HDAC (histone deacetylase) inhibitors show evidence as an antiaging strategy [84]. HDAC inhibitors have the potential to reverse the aging process that allows healthy aging [85].
Biomedicines 10 02515 g002
Figure 1. Epigenetic Mechanisms via DNA Methylation and histone modification. Epigenetics can be altered via developmental mechanisms, environmental chemicals, pharmaceuticals, aging, and diet. Some dietary sources can lead to a direct production of DNA methylation, allowing for the overexpression or repression of genes, thereby increasing the aging process.

5. Activation of Chaperons and the Proteolytic System against Aging

Loss of proteostasis is a common feature of aging that leads to protein aggregation, unfolding, oxidative damage, posttranslational modification, and an altered rate of protein turnover and, ultimately, to cellular dysfunction [86][87][88][89][90]. Two proteolytic systems—the ubiquitin–proteasome system (UPS) and autophagy–lysosome system (ALS)—and chaperones play a major role in maintaining proteostasis [91]. The alteration or deterioration of these pathways impairs normal cell functioning and cell physiology, causing aging [16]. Many studies have found proteostasis changes with age owing to reduced activity of heat-shocked protein chaperones [92][93]. To compensate for this decline, increasing the chaperone protein level has been shown to beneficially impact longevity in worms and flies [94][95][96][97]. A study reported that the aggregation of Hsp104, a chaperone, has been associated with aging and has increased the lifespan in Saccharomyces cerevisiae [98][99][100]. The UPS and ALS systems are the main proteolytic systems that influence the cellular fate and aging process [101][102]. The availability of the chaperone is extremely compromised in aged cells in which the proteostasis collapses by decreased G1-cyclin function that causes an irreversible arrest in G1, configuring a molecular pathway claiming proteostasis deterioration leads to cell senescence [103]. Promoting proteasomal activity via overexpression of the proteasomal β5 subunit either in Caenorhabditis elegans [104] or in human fibroblast [105] and the overexpression of Rpn11 in Drosophila melanogaster [106] increases the lifespan and stress resistance. The compound 18α-glycyrrhetinic acid and loss of IGF (insulin-like growth factor) signaling due to mutated daf-2 induce proteasomal activation and extend the lifespan of Caenorhabditis elegans [107]. Spermidine, metformin, rapamycin, and resveratrol are pharmaceutical approaches well-known to activate the autophagy system [108]. In a recent study, it was found that minocycline, JZL184, monorden, and paxilline directly targeted the 18S rRNA/ribosome, FAAH-4, Hsp90, and the SLO-1 BK channel, significantly increasing the lifespan of Caenorhabditis elegans [109]. The proteostatic system governs the synthesis and conformation of target proteins, and the ubiquitin—proteasome system and autophagy act as the main scavengers of misfolded or excessive proteins. The main cause of Alzheimer’s disease is the accumulation of misfolded proteins as Aβ plaques and tau aggregates owing to dysregulation of proteostasis, which contributes to the accumulation of proteotoxins in Alzheimer’s disease [110]. It has been reported that a decrease in the efficiency of the autophagy and ubiquitin—proteasome systems might lead to aging and neurodegenerative diseases such as AD, PD, and ALS [111]. The prion diseases in mammals are related to altered versions of PrPc (cellular), which is a key component of the infectious agent responsible for transmission, and the disease-associated version of PrPc can be partially resistant to the protease–digestion system, designated PrPsc (scrapie) [112]. Various cellular components, predominantly chaperones such as Hsp104, Hsp40s, HSP42, and HSP70s, can lead to the curing of yeast prions by their deficiency or overproduction. These studies have revealed the requirements for prion propagation and conditions that affect prion stability, which have led to the discovery of anti-prion systems. Btn2p, a component of the yeast anti-prion system, has the aggregate-sequestering abilities; it can cure an artificial and natural yeast prion, and works on a variety of non-prion aggregates as well [113]. This system might be advantageous for neurodegenerative diseases that result from aggregates of proteo-toxins.

References

  1. Rojo, L.E.; Fernández, J.A.; Maccioni, A.A.; Jimenez, J.M.; Maccioni, R.B. Neuroin flammation: Implications for the Pathogenesis and Molecular Diagnosis of Alzheimer’s Disease. Arch. Med. Res. 2008, 39, 1–16.
  2. Franceschi, C.; Campisi, J. Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases. J. Gerontol. Ser. A 2014, 69, S4–S9.
  3. Howcroft, T.K.; Campisi, J.; Louis, G.B.; Smith, M.T.; Wise, B.; Wyss-Coray, T.; Augustine, A.D.; McElhaney, J.E.; Kohanski, R.; Sierra, F. The role of inflammation in age-related disease. Aging 2013, 5, 84–93.
  4. De Magalhães, J.P.; Curado, J.; Church, G. Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics 2009, 25, 875–881.
  5. Kriete, A.; Mayo, K.L.; Yalamanchili, N.; Beggs, W.; Bender, P.; Kari, C.; Rodeck, U. Cell autonomous expression of inflammatory genes in biologically aged fibroblasts associated with elevated NF-kappaB activity. Immun. Ageing 2008, 5, 5.
  6. Minciullo, P.L.; Catalano, A.; Mandraffino, G.; Casciaro, M.; Crucitti, A.; Maltese, G.; Morabito, N.; Lasco, A.; Gangemi, S.; Basile, G. Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity. Arch. Immunol. Ther. Exp. 2016, 64, 111–126.
  7. Ventura, M.T.; Casciaro, M.; Gangemi, S.; Buquicchio, R. Immunosenescence in aging: Between immune cells depletion and cytokines up-regulation. Clin. Mol. Allergy 2017, 15, 21.
  8. Rea, I.M.; Gibson, D.S.; McGilligan, V.; McNerlan, S.E.; Alexander, H.D.; Ross, O.A. Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front. Immunol. 2018, 9, 586.
  9. Sanada, F.; Taniyama, Y.; Muratsu, J.; Otsu, R.; Shimizu, H.; Rakugi, H.; Morishita, R. Source of Chronic Inflammation in Aging. Front. Cardiovasc. Med. 2018, 5, 12.
  10. Chung, H.Y.; Ki, W.C.; Lee, E.K.; Chung, K.W.; Chung, S.; Lee, B.; Seo, A.Y.; Chung, J.H.; Jung, Y.S.; Im, E.; et al. Redefining Chronic Inflammation in Aging and Age-Related Diseases: Proposal of the Senoinflammation Concept. Aging Dis. 2019, 10, 367–382.
  11. Neves, J.M.; Sousa-Victor, P. Regulation of inflammation as an anti-aging intervention. FEBS J. 2020, 287, 43–52.
  12. Coppé, J.-P.; Desprez, P.-Y.; Krtolica, A.; Campisi, J. The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression. Annu. Rev. Pathol. Mech. Dis. 2010, 5, 99–118.
  13. Jurk, D.; Wilson, C.; Passos, J.F.; Oakley, F.; Correia-Melo, C.; Greaves, L.; Saretzki, G.; Fox, C.; Lawless, C.; Anderson, R.; et al. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nat. Commun. 2014, 5, 4172.
  14. Vitale, G.; Salvioli, S.; Franceschi, C. Oxidative stress and the ageing endocrine system. Nat. Rev. Endocrinol. 2013, 9, 228–240.
  15. Youm, Y.-H.; Grant, R.W.; McCabe, L.R.; Albarado, D.C.; Nguyen, K.Y.; Ravussin, A.; Pistell, P.; Newman, S.; Carter, R.; Laque, A.; et al. Canonical Nlrp3 Inflammasome Links Systemic Low-Grade Inflammation to Functional Decline in Aging. Cell Metab. 2013, 18, 519–532.
  16. López-Otín, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. The Hallmarks of Aging. Cell 2013, 153, 1194–1217.
  17. He, C.; Tsuchiyama, S.K.; Nguyen, Q.T.; Plyusnina, E.N.; Terrill, S.R.; Sahibzada, S.; Patel, B.; Faulkner, A.R.; Shaposhnikov, M.; Tian, R.; et al. Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import. PLoS Genet. 2014, 10, e1004860.
  18. Ching, T.-T.; Chiang, W.-C.; Chen, C.-S.; Hsu, A.-L. Celecoxib extends C. elegans lifespan via inhibition of insulin-like signaling but not cyclooxygenase-2 activity. Aging Cell 2011, 10, 506–519.
  19. Strong, R.; Miller, R.A.; Astle, C.M.; Floyd, R.A.; Flurkey, K.; Hensley, K.L.; Javors, M.A.; Leeuwenburgh, C.; Nelson, J.F.; Ongini, E.; et al. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell 2008, 7, 641–650.
  20. Lee, M.E.; Kim, S.R.; Lee, S.; Jung, Y.-J.; Choi, S.S.; Kim, W.J.; Han, J.A. Cyclooxygenase-2 inhibitors modulate skin aging in a catalytic activity-independent manner. Exp. Mol. Med. 2012, 44, 536–544.
  21. Kalonia, H.; Kumar, P.; Kumar, A. Licofelone attenuates quinolinic acid induced Huntington like symptoms: Possible behavioral, biochemical and cellular alterations. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2011, 35, 607–615.
  22. Asanuma, M.; Miyazaki, I.; Diaz-Corrales, F.J.; Ogawa, N. Quinone formation as dopaminergic neuron-specific oxidative stress in the pathogenesis of sporadic Parkinson’s disease and neurotoxin-induced parkinsonism. Acta Medica Okayama 2004, 58, 221–233.
  23. Black, P.H. Stress and the inflammatory response: A review of neurogenic inflammation. Brain Behav. Immun. 2002, 16, 622–653.
  24. Choi, S.H.; Aid, S.; Caracciolo, L.; Sakura Minami, S.; Niikura, T.; Matsuoka, Y.; Turner, R.S.; Mattson, M.P.; Bosetti, F. Cyclooxygenase-1 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer’s disease. J. Neurochem. 2013, 124, 59–68.
  25. Calfio, C.; Gonzalez, A.; Singh, S.K.; Rojo, L.E.; Maccioni, R.B. The Emerging Role of Nutraceuticals and Phytochemicals in the Prevention and Treatment of Alzheimer’s Disease. J. Alzheimer’s Dis. 2020, 77, 33–51.
  26. Veurink, G.; Perry, G.; Singh, S.K. Role of antioxidants and a nutrient rich diet in Alzheimer’s disease. Open Biol. 2020, 10, 200084.
  27. Minois, N. Molecular Basis of the ‘Anti-Aging’ Effect of Spermidine and Other Natural Polyamines—A Mini-Review. Gerontology 2014, 60, 319–326.
  28. Madeo, F.; Carmona-Gutierrez, D.; Kepp, O.; Kroemer, G. Spermidine delays aging in humans. Aging 2018, 10, 2209–2211.
  29. Phillips, T.; Leeuwenburgh, C. Lifelong Aspirin Supplementation as a Means to Extending Life Span. Rejuvenation Res. 2004, 7, 243–252.
  30. Ayyadevara, S.; Bharill, P.; Dandapat, A.; Hu, C.; Khaidakov, M.; Mitra, S.; Shmookler Reis, R.J.; Mehta, J.L. Aspirin inhibits oxidant stress, reduces age-associated functional declines, and extends lifespan of Caenorhabditis elegans. Antioxid. Redox Signal. 2013, 18, 481–490.
  31. Nadon, N.L.; Strong, R.; Miller, R.A.; Harrison, D.E. NIA Interventions Testing Program: Investigating Putative Aging Intervention Agents in a Genetically Heterogeneous Mouse Model. eBioMedicine 2017, 21, 3–4.
  32. Orhan, H.; Doğruer, D.; Cakir, B.; Şahin, G.; Şahin, M. The in vitro effects of new non-steroidal antiinflammatory compounds on antioxidant system of human erythrocytes. Exp. Toxicol. Pathol. 1999, 51, 397–402.
  33. Danilov, A.; Shaposhnikov, M.; Shevchenko, O.; Zemskaya, N.; Zhavoronkov, A.; Moskalev, A. Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster longevity. Oncotarget 2015, 6, 19428–19444.
  34. Hosseini, S.; Abdollahi, M.; Azizi, G.; Fattahi, M.J.; Rastkari, N.; Zavareh, F.T.; Aghazadeh, Z.; Mirshafiey, A. Anti-aging effects of M2000 (β-D-mannuronic acid) as a novel immunosuppressive drug on the enzymatic and non-enzymatic oxidative stress parameters in an experimental model. J. Basic Clin. Physiol. Pharmacol. 2017, 28, 249–255.
  35. Waditee-Sirisattha, R.; Kageyama, H. Protective effects of mycosporine-like amino acid-containing emulsions on UV-treated mouse ear tissue from the viewpoints of antioxidation and antiglycation. J. Photochem. Photobiol. B 2021, 223, 112296.
  36. Kageyama, H.; Waditee-Sirisattha, R. Antioxidative, Anti-Inflammatory, and Anti-Aging Properties of Mycosporine-Like Amino Acids: Molecular and Cellular Mechanisms in the Protection of Skin-Aging. Mar. Drugs 2019, 17, 222.
  37. Kumar Singh, S.; Barreto, G.E.; Aliev, G.; Echeverria, V. Ginkgo biloba as an Alternative Medicine in the Treatment of Anxiety in Dementia and other Psychiatric Disorders. Curr. Drug. Metab. 2017, 18, 112–119.
  38. Singh, S.K.; Srikrishna, S.; Castellani, R.J.; Perry, G. Antioxidants in the prevention and treatment of alzheimer’s disease. In Nutritional Antioxidant Therapies: Treatments and Perspectives; Springer International Publishing: Berlin/Heidelberg, Germany, 2018; pp. 523–553.
  39. Singh, S.K.; Srivastav, S.; Castellani, R.J.; Plascencia-Villa, G.; Perry, G. Neuroprotective and Antioxidant Effect of Ginkgo biloba Extract Against AD and Other Neurological Disorders. Neurotherapeutics 2019, 16, 666–674.
  40. Mishra, S.; Mishra, S.K.; Singh, S.K. Ayurveda and Yoga practices: A synergistic approach for the treatment of Alzheimer’s disease. Eur. J. Biol. Res. 2020, 11, 65–74.
  41. Pietta, P.G. Flavonoids as Antioxidants. J. Nat. Prod. 2000, 63, 1035–1042.
  42. Lobo, V.; Patil, A.; Phatak, A.; Chandra, N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn. Rev. 2010, 4, 118–126.
  43. Kampkötter, A.; Timpel, C.; Zurawski, R.F.; Ruhl, S.; Chovolou, Y.; Proksch, P.; Wätjen, W. Increase of stress resistance and lifespan of Caenorhabditis elegans by quercetin. Comp. Biochem. Physiol. Part B Biochem. Mol. Biol. 2008, 149, 314–323.
  44. Sugawara, T.; Sakamoto, K. Quercetin enhances motility in aged and heat-stressed Caenorhabditis elegans nematodes by modulating both HSF-1 activity, and insulin-like and p38-MAPK signalling. PLoS ONE 2020, 15, e0238528.
  45. Pietsch, K.; Saul, N.; Swain, S.C.; Menzel, R.; Steinberg, C.E.; Stürzenbaum, S.R. Meta-analysis of global transcriptomics suggests that conserved genetic pathways are responsible for quercetin and tannic acid mediated longevity in C. elegans. Front. Genet. 2012, 3, 48.
  46. Proshkina, E.; Lashmanova, E.; Dobrovolskaya, E.; Zemskaya, N.; Kudryavtseva, A.; Shaposhnikov, M.; Moskalev, A. Geroprotective and Radioprotective Activity of Quercetin, (-)-Epicatechin, and Ibuprofen in Drosophila melanogaster. Front. Pharmacol. 2016, 7, 505.
  47. Končič, M.; Rajić, Z.; Petrič, N.; Zorc, B. Antioxidant activity of NSAID hydroxamic acids. Acta Pharm. 2009, 59, 235–242.
  48. Orhan, H.; Şahin, G. In vitro effects of NSAIDS and paracetamolon oxidative stress-related parameters of human erythrocytes. Exp. Toxicol. Pathol. 2001, 53, 133–140.
  49. Peng, C.; Wang, X.; Chen, J.; Jiao, R.; Wang, L.; Li, Y.M.; Zuo, Y.; Liu, Y.; Lei, L.; Ma, K.Y.; et al. Biology of Ageing and Role of Dietary Antioxidants. BioMed Res. Int. 2014, 2014, 831841.
  50. O’Sullivan, R.J.; Karlseder, J. Telomeres: Protecting chromosomes against genome instability. Nat. Rev. Mol. Cell Biol. 2010, 11, 171–181.
  51. Lingner, J.; Cooper, J.P.; Cech, T.R. Telomerase and DNA end replication: No longer a lagging strand problem? Science 1995, 269, 1533–1534.
  52. Greider, C.W. Telomerase is processive. Mol. Cell. Biol. 1991, 11, 4572–4580.
  53. Cesare, A.J.; Reddel, R.R. Alternative lengthening of telomeres: Models, mechanisms and implications. Nat. Rev. Genet. 2010, 11, 319–330.
  54. Victorelli, S.; Passos, J.F. Telomeres and Cell Senescence—Size Matters Not. eBioMedicine 2017, 21, 14–20.
  55. Dodig, S.; Čepelak, I.; Pavić, I. Hallmarks of senescence and aging. Biochem. Med. 2019, 29, 483–497.
  56. Cassidy, A.; De Vivo, I.; Liu, Y.; Han, J.; Prescott, J.; Hunter, D.J.; Rimm, E.B. Associations between diet, lifestyle factors, and telomere length in women. Am. J. Clin. Nutr. 2010, 91, 1273–1280.
  57. Prescott, J.; Kraft, P.; Chasman, D.I.; Savage, S.A.; Mirabello, L.; Berndt, S.I.; Weissfeld, J.L.; Han, J.; Hayes, R.B.; Chanock, S.J.; et al. Genome-Wide Association Study of Relative Telomere Length. PLoS ONE 2011, 6, e19635.
  58. Song, S.; Johnson, F.B. Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres. Genes 2018, 9, 201.
  59. Kuszel, L.; Trzeciak, T.; Richter, M.; Czarny-Ratajczak, M. Osteoarthritis and telomere shortening. J. Appl. Genet. 2015, 56, 169–176.
  60. Carlquist, J.F.; Knight, S.; Cawthon, R.M.; Le, V.; Bunch, T.J.; Horne, B.D.; Rollo, J.S.; Huntinghouse, J.A.; Muhlestein, J.B.; Anderson, J.L. Shortened telomere length is associated with paroxysmal atrial fibrillation among cardiovascular patients enrolled in the Intermountain Heart Collaborative Study. Hear. Rhythm 2016, 13, 21–27.
  61. Hunt, S.C.; Kimura, M.; Hopkins, P.N.; Carr, J.J.; Heiss, G.; Province, M.A.; Aviv, A. Leukocyte Telomere Length and Coronary Artery Calcium. Am. J. Cardiol. 2015, 116, 214–218.
  62. Blasco, M.A. Telomere length, stem cells and aging. Nat. Chem. Biol. 2007, 3, 640–649.
  63. Pereira, B.; Ferreira, M.G. Sowing the seeds of cancer: Telomeres and age-associated tumorigenesis. Curr. Opin. Oncol. 2013, 25, 93–98.
  64. Wang, S.; Madu, C.O.; Lu, Y. Telomere and Its Role in Diseases. Oncomedicine 2019, 4, 1–9.
  65. Bernades de Jesus, B.; Schneeberger, K.; Vera, E.; Tejera, A.; Harley, C.B.; Blasco, M.A. The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence. Aging Cell 2011, 10, 604–621.
  66. Bär, C.; Huber, N.; Beier, F.; Blasco, M.A. Therapeutic effect of androgen therapy in a mouse model of aplastic anemia produced by short telomeres. Haematologica 2015, 100, 1267–1274.
  67. Calado, R.T.; Yewdell, W.T.; Wilkerson, K.L.; Regal, J.A.; Kajigaya, S.; Stratakis, C.A.; Young, N.S. Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. Blood J. Am. Soc. Hematol. 2009, 114, 2236–2243.
  68. de Jesus, B.B.; Vera, E.; Schneeberger, K.; Tejera, A.M.; Ayuso, E.; Bosch, F.; Blasco, M.A. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol. Med. 2012, 4, 691–704.
  69. Raghavan, P.R. Metadichol®: A Novel Nanolipid Formulation That Inhibits SARS-CoV-2 and a Multitude of Pathological Viruses In Vitro. BioMed Res. Int. 2020.
  70. Tsoukalas, D.; Fragkiadaki, P.; Docea, A.O.; Alegakis, A.K.; Sarandi, E.; Thanasoula, M.; Spandidos, D.A.; Tsatsakis, A.; Razgonova, M.P.; Calina, D. Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives. Mol. Med. Rep. 2019, 20, 3701–3708.
  71. Shay, J.W. Role of Telomeres and Telomerase in Aging and Cancer. Cancer Discov. 2016, 6, 584–593.
  72. Sedivy, J.M.; Banumathy, G.; Adams, P.D. Aging by epigenetics—A consequence of chromatin damage? Exp. Cell. Res. 2008, 314, 1909–1917.
  73. Feser, J.; Tyler, J. Chromatin structure as a mediator of aging. FEBS Lett. 2011, 585, 2041–2048.
  74. O’Sullivan, R.J.; Karlseder, J. The great unravelling: Chromatin as a modulator of the aging process. Trends Biochem. Sci. 2012, 37, 466–476.
  75. Imai, S.-I.; Armstrong, C.M.; Kaeberlein, M.; Guarente, L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 2000, 403, 795–800.
  76. Longo, V.D. Linking sirtuins, IGF-I signaling, and starvation. Exp. Gerontol. 2009, 44, 70–74.
  77. Zhang, L.; Xie, W.J.; Liu, S.; Meng, L.; Gu, C.; Gao, Y.Q. DNA Methylation Landscape Reflects the Spatial Organization of Chromatin in Different Cells. Biophys. J. 2017, 113, 1395–1404.
  78. McClay, J.L.; Aberg, K.A.; Clark, S.L.; Nerella, S.; Kumar, G.; Xie, L.Y.; Hudson, A.D.; Harada, A.; Hultman, C.M.; Magnusson, P.K.; et al. A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects. Hum. Mol. Genet. 2014, 23, 1175–1185.
  79. Teschendorff, A.E.; Menon, U.; Gentry-Maharaj, A.; Ramus, S.J.; Weisenberger, D.J.; Shen, H.; Campan, M.; Noushmehr, H.; Bell, C.G.; Maxwell, A.P.; et al. Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res. 2010, 20, 440–446.
  80. Horvath, S. DNA methylation age of human tissues and cell types. Genome Biol. 2013, 14, R115.
  81. Pal, S.; Tyler, J.K. Epigenetics and aging. Sci. Adv. 2016, 2.
  82. Jylhava, J. Determinants of longevity: Genetics, biomarkers and therapeutic approaches. Current Pharmaceutical Design 2014, 20, 6058–6070.
  83. Morselli, E.; Mariño, G.; Bennetzen, M.V.; Eisenberg, T.; Megalou, E.; Schroeder, S.; Cabrera, S.; Bénit, P.; Rustin, P.; Criollo, A.; et al. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. J. Cell Biol. 2011, 192, 615–629.
  84. Pasyukova, E.G.; Vaiserman, A.M. HDAC inhibitors: A new promising drug class in anti-aging research. Mech. Ageing Dev. 2017, 166, 6–15.
  85. McIntyre, R.L.; Daniels, E.G.; Molenaars, M.; Houtkooper, R.H.; Janssens, G.E. From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs. EMBO Mol. Med. 2019, 11, e9854.
  86. Hetz, C.; Chevet, E.; Oakes, S.A. Proteostasis control by the unfolded protein response. Nat. Cell Biol. 2015, 17, 829–838.
  87. Cannizzo, E.S.; Clement, C.C.; Morozova, K.; Valdor, R.; Kaushik, S.; Almeida, L.N.; Follo, C.; Sahu, R.; Cuervo, A.M.; Macian, F.; et al. Age-Related Oxidative Stress Compromises Endosomal Proteostasis. Cell Rep. 2012, 2, 136–149.
  88. Brehm, A.; Krüger, E. Dysfunction in protein clearance by the proteasome: Impact on autoinflammatory diseases. Semin. Immunopathol. 2015, 37, 323–333.
  89. Dai, D.-F.; Karunadharma, P.P.; Chiao, Y.A.; Basisty, N.; Crispin, D.; Hsieh, E.J.; Chen, T.; Gu, H.; Djukovic, D.; Raftery, D.; et al. Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart. Aging Cell 2014, 13, 529–539.
  90. Gong, Z.; Tasset, I. Humanin enhances the cellular response to stress by activation of chaperone-mediated autophagy. Oncotarget 2018, 9, 10832–10833.
  91. Amm, I.; Sommer, T.; Wolf, D.H. Protein quality control and elimination of protein waste: The role of the ubiquitin–proteasome system. Biochim. Biophys. Acta BBA—Mol. Cell Res. 2013, 1843, 182–196.
  92. Koga, H.; Kaushik, S.; Cuervo, A.M. Protein homeostasis and aging: The importance of exquisite quality control. Ageing Res. Rev. 2011, 10, 205–215.
  93. Calderwood, S.K.; Murshid, A.; Prince, T. The Shock of Aging: Molecular Chaperones and the Heat Shock Response in Longevity and Aging—A Mini-Review. Gerontology 2009, 55, 550–558.
  94. Morrow, G.; Samson, M.; Michaud, S.; Tanguay, R.M. Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress. FASEB J. 2004, 18, 598–599.
  95. Walker, G.A.; Lithgow, G.J. Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell 2003, 2, 131–139.
  96. Chiang, W.C.; Ching, T.T.; Lee, H.C.; Mousigian, C.; Hsu, A.L. HSF-1 Regulators DDL-1/2 Link Insulin-like Signaling to Heat-Shock Responses and Modulation of Longevity. Cell 2012, 148, 322–334.
  97. Hsu, A.-L.; Murphy, C.T.; Kenyon, C. Regulation of Aging and Age-Related Disease by DAF-16 and Heat-Shock Factor. Science 2003, 300, 1142–1145.
  98. Ünal, E.; Kinde, B.; Amon, A. Gametogenesis Eliminates Age-Induced Cellular Damage and Resets Life Span in Yeast. Science 2011, 332, 1554–1557.
  99. Erjavec, N.; Larsson, L.; Grantham, J.; Nyström, T. Accelerated aging and failure to segregate damaged proteins in Sir2 mutants can be suppressed by overproducing the protein aggregation-remodeling factor Hsp104p. Genes Dev. 2007, 21, 2410–2421.
  100. Kaeberlein, M.; Kirkland, K.T.; Fields, S.; Kennedy, B.K. Genes determining yeast replicative life span in a long-lived genetic background. Mech. Ageing Dev. 2005, 126, 491–504.
  101. Andersson, V.; Hanzén, S.; Liu, B.; Molin, M.; Nyström, T. Enhancing protein disaggregation restores proteasome activity in aged cells. Aging 2013, 5, 802–812.
  102. Press, M.; Jung, T.; König, J.; Grune, T.; Höhn, A. Protein aggregates and proteostasis in aging: Amylin and β-cell function. Mech. Ageing Dev. 2019, 177, 46–54.
  103. Moreno, D.; Jenkins, K.; Morlot, S.; Charvin, G.; Csikasz-Nagy, A.; Aldea, M. Proteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1. eLife 2019, 8, 48240.
  104. Chondrogianni, N.; Georgila, K.; Kourtis, N.; Tavernarakis, N.; Gonos, E.S. 20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans. FASEB J. 2015, 29, 611–622.
  105. Chondrogianni, N.; Tzavelas, C.; Pemberton, A.J.; Nezis, I.P.; Rivett, A.J.; Gonos, E.S. Overexpression of Proteasome β5 Assembled Subunit Increases the Amount of Proteasome and Confers Ameliorated Response to Oxidative Stress and Higher Survival Rates*. J. Biol. Chem. 2005, 280, 11840–11850.
  106. Tonoki, A.; Kuranaga, E.; Tomioka, T.; Hamazaki, J.; Murata, S.; Tanaka, K.; Miura, M. Genetic Evidence Linking Age-Dependent Attenuation of the 26S Proteasome with the Aging Process. Mol. Cell. Biol. 2009, 29, 1095–1106.
  107. Papaevgeniou, N.; Sakellari, M.; Jha, S.; Tavernarakis, N.; Holmberg, C.I.; Gonos, E.S.; Chondrogianni, N. 18α-Glycyrrhetinic acid proteasome activator decelerates aging and Alzheimer’s disease progression in Caenorhabditis elegans and neuronal cultures. Antioxid. Redox Signal. 2016, 25, 855–869.
  108. Eisenberg, T.; Knauer, H.; Schauer, A.; Büttner, S.; Ruckenstuhl, C.; Carmona-Gutierrez, D.; Ring, J.; Schroeder, S.; Magnes, C.; Antonacci, L.; et al. Induction of autophagy by spermidine promotes longevity. Nat. Cell Biol. 2009, 11, 1305–1314.
  109. Kim, E.J.E.; Lee, S.-J.V. Recent progresses on anti-aging compounds and their targets in Caenorhabditis elegans. Transl. Med. Aging 2019, 3, 121–124.
  110. Cheng, J.; North, B.J.; Zhang, T.; Dai, X.; Tao, K.; Guo, J.; Wei, W. The emerging roles of protein homeostasis-governing pathways in Alzheimer’s disease. Aging Cell 2018, 17, e12801.
  111. Höhn, A.; Tramutola, A.; Cascella, R. Proteostasis Failure in Neurodegenerative Diseases: Focus on Oxidative Stress. Oxidative Med. Cell. Longev. 2020, 2020, 5497046.
  112. Sigurdson, C.J.; Bartz, J.C.; Glatzel, M. Cellular and Molecular Mechanisms of Prion Disease. Annu. Rev. Pathol. Mech. Dis. 2019, 14, 497–516.
  113. Wickner, R.B.; Bezsonov, E.E.; Son, M.; Ducatez, M.; DeWilde, M.; Edskes, H.K. Anti-Prion Systems in Yeast and Inositol Polyphosphates. Biochemistry 2018, 57, 1285–1292.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Neurosciences
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Shailendra Kumar Mishra
,
Vyshnavy Balendra
,
Josephine Esposto
,
Ahmad A. Obaid
,
Ricardo B. Maccioni
,
Niraj Kumar Jha
,
George Perry
,
Mahmoud Moustafa
,
Mohammed Al-Shehri
,
Mahendra P. Singh
,
Anmar Anwar Khan
,
Emanuel Vamanu
,
Sandeep Kumar Singh
View Times: 507
Revisions: 2 times (View History)
Update Date: 08 Nov 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback