López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186:243–78.

PubMed  Google Scholar 

Dey P, Chaudhuri SR, Efferth T, Pal S. The intestinal 3M (microbiota, metabolism, metabolome) zeitgeist - from fundamentals to future challenges. Free Radic Biol Med. 2021;176:265–85.

CAS  PubMed  Google Scholar 

Livshits G, Kalinkovich A. Inflammaging as a common ground for the development and maintenance of sarcopenia, obesity, cardiomyopathy and dysbiosis. Ageing Res Rev. 2019;56:100980.

CAS  PubMed  Google Scholar 

Waldbaum JDH, Xhumari J, Akinsuyi OS, Arjmandi B, Anton S, Roesch LFW. Association between dysbiosis in the gut microbiota of primary osteoporosis patients and bone loss. Aging Dis. 2023;14:2081–95.

PubMed  PubMed Central  Google Scholar 

Wang T, Shi Z, Ren H, Xu M, Lu J, Yang F, Ye C, Wu K, Chen M, Xu X, et al. Divergent age-associated and metabolism-associated gut microbiome signatures modulate cardiovascular disease risk. Nat Med. 2024;30:1722–31.

CAS  PubMed  Google Scholar 

Chen S, Zhang Z, Liu S, Chen T, Lu Z, Zhao W, Mou X, Liu S. Consistent signatures in the human gut microbiome of longevous populations. Gut Microbes. 2024;16:2393756.

PubMed  PubMed Central  Google Scholar 

Pang S, Chen X, Lu Z, Meng L, Huang Y, Yu X, Huang L, Ye P, Chen X, Liang J, et al. Longevity of centenarians is reflected by the gut microbiome with youth-associated signatures. Nat Aging. 2023;3:436–49.

PubMed  Google Scholar 

Sato Y, Atarashi K, Plichta DR, Arai Y, Sasajima S, Kearney SM, Suda W, Takeshita K, Sasaki T, Okamoto S, et al. Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians. Nature. 2021;599:458–64.

CAS  PubMed  Google Scholar 

Bárcena C, Valdés-Mas R, Mayoral P, Garabaya C, Durand S, Rodríguez F, Fernández-García MT, Salazar N, Nogacka AM, Garatachea N, et al. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice. Nat Med. 2019;25:1234–42.

PubMed  Google Scholar 

Novelle MG, Naranjo-Martínez B, López-Cánovas JL, Díaz-Ruiz A. Fecal microbiota transplantation, a tool to transfer healthy longevity. Ageing Res Rev. 2025;103:102585.

CAS  PubMed  Google Scholar 

Barzilai N, Guarente L, Kirkwood TB, Partridge L, Rando TA, Slagboom PE. The place of genetics in ageing research. Nat Rev Genet. 2012;13:589–94.

CAS  PubMed  Google Scholar 

van den Berg N, Beekman M, Smith KR, Janssens A, Slagboom PE. Historical demography and longevity genetics: back to the future. Ageing Res Rev. 2017;38:28–39.

PubMed  Google Scholar 

Beard JR, Officer A, de Carvalho IA, Sadana R, Pot AM, Michel JP, Lloyd-Sherlock P, Epping-Jordan JE, Peeters G, Mahanani WR, et al. The World report on ageing and health: a policy framework for healthy ageing. Lancet. 2016;387:2145–54.

PubMed  Google Scholar 

Rosoff DB, Mavromatis LA, Bell AS, Wagner J, Jung J, Marioni RE, Davey Smith G, Horvath S, Lohoff FW. Multivariate genome-wide analysis of aging-related traits identifies novel loci and new drug targets for healthy aging. Nat Aging. 2023;3:1020–35.

CAS  PubMed  PubMed Central  Google Scholar 

Newell Stamper BL, Cypser JR, Kechris K, Kitzenberg DA, Tedesco PM, Johnson TE. Movement decline across lifespan of Caenorhabditis elegans mutants in the insulin/insulin-like signaling pathway. Aging Cell. 2018;7(1):e12704.

Google Scholar 

Hamczyk MR, Nevado RM, Barettino A, Fuster V, Andrés V. Biological versus chronological aging: JACC Focus Seminar. J Am Coll Cardiol. 2020;75:919–30.

CAS  PubMed  Google Scholar 

Timmers P, Tiys ES, Sakaue S, Akiyama M, Kiiskinen TTJ, Zhou W, Hwang SJ, Yao C, Deelen J, Levy D, et al. Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging. Nat Aging. 2022;2:19–30.

PubMed  Google Scholar 

Li T, Yang S, Liu X, Li Y, Gu Z, Jiang Z. Dietary neoagarotetraose extends lifespan and impedes brain aging in mice via regulation of microbiota-gut-brain axis. J Adv Res. 2023;52:119–34.

CAS  PubMed  PubMed Central  Google Scholar 

Khan R, Di Gesù CM, Lee J, McCullough LD. The contribution of age-related changes in the gut-brain axis to neurological disorders. Gut Microbes. 2024;16:2302801.

PubMed  PubMed Central  Google Scholar 

Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 2019;16:461–78.

PubMed  Google Scholar 

Kapoor B, Biswas P, Gulati M, Rani P, Gupta R. Gut microbiome and Alzheimer’s disease: what we know and what remains to be explored. Ageing Res Rev. 2024;102:102570.

CAS  PubMed  Google Scholar 

Xia Y, Xiao Y, Wang ZH, Liu X, Alam AM, Haran JP, McCormick BA, Shu X, Wang X, Ye K. Bacteroides Fragilis in the gut microbiomes of Alzheimer’s disease activates microglia and triggers pathogenesis in neuronal C/EBPβ transgenic mice. Nat Commun. 2023;14:5471.

CAS  PubMed  PubMed Central  Google Scholar 

Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA. 2017;318:1925–6.

PubMed  Google Scholar 

Burgess S, Thompson SG. Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol. 2015;181:251–60.

PubMed  PubMed Central  Google Scholar 

Carter AR, Sanderson E, Hammerton G, Richmond RC, Davey Smith G, Heron J, Taylor AE, Davies NM, Howe LD. Mendelian randomisation for mediation analysis: current methods and challenges for implementation. Eur J Epidemiol. 2021;36:465–78.

PubMed  PubMed Central  Google Scholar 

Lopera-Maya EA, Kurilshikov A, van der Graaf A, Hu S, Andreu-Sánchez S, Chen L, Vila AV, Gacesa R, Sinha T, Collij V, et al. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project. Nat Genet. 2022;54:143–51.

CAS  PubMed  Google Scholar 

Timmers PR, Mounier N, Lall K, Fischer K, Ning Z, Feng X, Bretherick AD, Clark DW, Shen X, Esko T. Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances. Elife. 2019;8:e39856.

PubMed  PubMed Central  Google Scholar 

Pilling LC, Kuo CL, Sicinski K, Tamosauskaite J, Kuchel GA, Harries LW, Herd P, Wallace R, Ferrucci L, Melzer D. Human longevity: 25 genetic loci associated in 389,166 UK biobank participants. Aging (Albany NY). 2017;9:2504–20.

CAS  PubMed  Google Scholar 

Zenin A, Tsepilov Y, Sharapov S, Getmantsev E, Menshikov LI, Fedichev PO, Aulchenko Y. Identification of 12 genetic loci associated with human healthspan. Commun Biol. 2019;2:41.

PubMed  PubMed Central  Google Scholar 

Pilling LC, Atkins JL, Bowman K, Jones SE, Tyrrell J, Beaumont RN, Ruth KS, Tuke MA, Yaghootkar H, Wood AR, et al. Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants. Aging (Albany NY). 2016;8:547–60.

CAS  PubMed  Google Scholar 

Deelen J, Evans DS, Arking DE, Tesi N, Nygaard M, Liu X, Wojczynski MK, Biggs ML, van der Spek A, Atzmon G, et al. A meta-analysis of genome-wide association studies identifies multiple longevity genes. Nat Commun. 2019;10:3669.

PubMed  PubMed Central  Google Scholar 

McCartney DL, Min JL, Richmond RC, Lu AT, Sobczyk MK, Davies G, Broer L, Guo X, Jeong A, Jung J, et al. Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging. Genome Biol. 2021;22:194.

CAS  PubMed  PubMed Central  Google Scholar 

Western D, Timsina J, Wang L, Wang C, Yang C, Phillips B, Wang Y, Liu M, Ali M, Beric A, et al. Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease. Nat Genet. 2024;56:2672–84.

CAS  PubMed  Google Scholar 

McCartney DL, Hillary RF, Stevenson AJ, Ritchie SJ, Walker RM, Zhang Q, Morris SW, Bermingham ML, Campbell A, Murray AD, et al. Epigenetic prediction of complex traits and death. Genome Biol. 2018;19:136.

PubMed  PubMed Central  Google Scholar 

Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:693–8.

CAS  PubMed  PubMed Central  Google Scholar 

Martin L, Boutwell BB, Messerlian C, Adams CD. Mendelian randomization reveals apolipoprotein B shortens healthspan and possibly increases risk for Alzheimer’s disease. Commun Biol. 2024;7:230.

PubMed  PubMed Central  Google Scholar 

Barcena C, Valdes-Mas R, Mayoral P, et al. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice. Nat Med. 2019;25:1234–1242.

Chen S, Chen W, Wang X, Liu S. Mendelian randomization analyses support causal relationships between gut microbiome and longevity. J Transl Med. 2024;22:1032.

CAS  PubMed