TOMM40 genetic variants associated with healthy aging and longevity: a systematic review

BMC Geriatr. 2022 Aug 13;22(1):667. doi: 10.1186/s12877-022-03337-4.


Introduction: Healthy aging relies on mitochondrial functioning because this organelle provides energy and diminishes oxidative stress. Single nucleotide polymorphisms (SNPs) in TOMM40, a critical gene that produces the outer membrane protein TOM40 of mitochondria, have been associated with mitochondrial dysfunction and neurodegenerative processes. Yet it is not clear whether or how the mitochondria may impact human longevity. We conducted this review to ascertain which SNPs have been associated with markers of healthy aging.

Methods: Using the PRISMA methodology, we conducted a systematic review on PubMed and Embase databases to identify associations between TOMM40 SNPs and measures of longevity and healthy aging.

Results: Twenty-four articles were selected. The TOMM40 SNPs rs2075650 and rs10524523 were the two most commonly identified and studied SNPs associated with longevity. The outcomes associated with the TOMM40 SNPs were changes in BMI, brain integrity, cognitive functions, altered inflammatory network, vulnerability to vascular risk factors, and longevity.

Discussions: Our systematic review identified multiple TOMM40 SNPs potentially associated with healthy aging. Additional research can help to understand mechanisms in aging, including resilience, prevention of disease, and adaptation to the environment.

Keywords: Aging; Healthy aging; Longevity; Systematic review; TOMM40.

Publication types

  • Systematic Review

MeSH terms

  • Aging / genetics
  • Healthy Aging* / genetics
  • Humans
  • Longevity* / genetics
  • Membrane Transport Proteins / genetics
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Polymorphism, Single Nucleotide / genetics


  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • TOMM40 protein, human