Folic acid and homocysteine in age-related disease

Mark P. Mattson, Inna I. Kruman, Wenzhen Duan

Research output: Contribution to journalArticle

Abstract

It has been known for decades that babies born to women that have a dietary deficiency in folic acid (folate) are at increased risk for birth defects, and that the nervous system is particularly susceptible to such defects. Folate deficiency in adults can increase risk of coronary artery disease, stroke, several types of cancer, and possibly Alzheimer's and Parkinson's diseases. Recent findings have begun to reveal the cellular and molecular mechanisms whereby folate counteracts age-related disease. An increase in homocysteine levels is a major consequence of folate deficiency that may have adverse effects on multiple organ systems during aging. Humans with inherited defects in enzymes involved in homocysteine metabolism, including cystathionine β-synthase and 5,10-methylenetetrahydrofolate reductase, exhibit features of accelerated aging and a marked propensity for several age-related diseases. Homocysteine enhances accumulation of DNA damage by inducing a methyl donor deficiency state and impairing DNA repair. In mitotic cells such DNA damage can lead to cancer, while in postmitotic cells such as neurons it promotes cell death. The emerging data strongly suggest that elevated homocysteine levels increase the risk of multiple age-related diseases, and point to dietary supplementation with folate as a primary means of normalizing homocysteine levels and increasing healthspan.

Original languageEnglish (US)
Pages (from-to)95-111
Number of pages17
JournalAgeing Research Reviews
Volume1
Issue number1
DOIs
StatePublished - Feb 2002
Externally publishedYes

Fingerprint

Homocysteine
Folic Acid
DNA Damage
Defects
Folic Acid Deficiency
Cystathionine
DNA
Methylenetetrahydrofolate Reductase (NADPH2)
Aging of materials
Dietary Supplements
DNA Repair
Nervous System
Neurology
Cell death
Parkinson Disease
Coronary Artery Disease
Neoplasms
Alzheimer Disease
Metabolism
Cell Death

Keywords

  • DNA repair
  • Folate deficiency
  • Homocysteine

ASJC Scopus subject areas

  • Aging
  • Biochemistry

Cite this

Folic acid and homocysteine in age-related disease. / Mattson, Mark P.; Kruman, Inna I.; Duan, Wenzhen.

In: Ageing Research Reviews, Vol. 1, No. 1, 02.2002, p. 95-111.

Research output: Contribution to journalArticle

Mattson, Mark P. ; Kruman, Inna I. ; Duan, Wenzhen. / Folic acid and homocysteine in age-related disease. In: Ageing Research Reviews. 2002 ; Vol. 1, No. 1. pp. 95-111.
@article{ed38d15906f34c0caea7f594c03712e9,
title = "Folic acid and homocysteine in age-related disease",
abstract = "It has been known for decades that babies born to women that have a dietary deficiency in folic acid (folate) are at increased risk for birth defects, and that the nervous system is particularly susceptible to such defects. Folate deficiency in adults can increase risk of coronary artery disease, stroke, several types of cancer, and possibly Alzheimer's and Parkinson's diseases. Recent findings have begun to reveal the cellular and molecular mechanisms whereby folate counteracts age-related disease. An increase in homocysteine levels is a major consequence of folate deficiency that may have adverse effects on multiple organ systems during aging. Humans with inherited defects in enzymes involved in homocysteine metabolism, including cystathionine β-synthase and 5,10-methylenetetrahydrofolate reductase, exhibit features of accelerated aging and a marked propensity for several age-related diseases. Homocysteine enhances accumulation of DNA damage by inducing a methyl donor deficiency state and impairing DNA repair. In mitotic cells such DNA damage can lead to cancer, while in postmitotic cells such as neurons it promotes cell death. The emerging data strongly suggest that elevated homocysteine levels increase the risk of multiple age-related diseases, and point to dietary supplementation with folate as a primary means of normalizing homocysteine levels and increasing healthspan.",
keywords = "DNA repair, Folate deficiency, Homocysteine",
author = "Mattson, {Mark P.} and Kruman, {Inna I.} and Wenzhen Duan",
year = "2002",
month = "2",
doi = "10.1016/S0047-6374(01)00365-7",
language = "English (US)",
volume = "1",
pages = "95--111",
journal = "Ageing Research Reviews",
issn = "1568-1637",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Folic acid and homocysteine in age-related disease

AU - Mattson, Mark P.

AU - Kruman, Inna I.

AU - Duan, Wenzhen

PY - 2002/2

Y1 - 2002/2

N2 - It has been known for decades that babies born to women that have a dietary deficiency in folic acid (folate) are at increased risk for birth defects, and that the nervous system is particularly susceptible to such defects. Folate deficiency in adults can increase risk of coronary artery disease, stroke, several types of cancer, and possibly Alzheimer's and Parkinson's diseases. Recent findings have begun to reveal the cellular and molecular mechanisms whereby folate counteracts age-related disease. An increase in homocysteine levels is a major consequence of folate deficiency that may have adverse effects on multiple organ systems during aging. Humans with inherited defects in enzymes involved in homocysteine metabolism, including cystathionine β-synthase and 5,10-methylenetetrahydrofolate reductase, exhibit features of accelerated aging and a marked propensity for several age-related diseases. Homocysteine enhances accumulation of DNA damage by inducing a methyl donor deficiency state and impairing DNA repair. In mitotic cells such DNA damage can lead to cancer, while in postmitotic cells such as neurons it promotes cell death. The emerging data strongly suggest that elevated homocysteine levels increase the risk of multiple age-related diseases, and point to dietary supplementation with folate as a primary means of normalizing homocysteine levels and increasing healthspan.

AB - It has been known for decades that babies born to women that have a dietary deficiency in folic acid (folate) are at increased risk for birth defects, and that the nervous system is particularly susceptible to such defects. Folate deficiency in adults can increase risk of coronary artery disease, stroke, several types of cancer, and possibly Alzheimer's and Parkinson's diseases. Recent findings have begun to reveal the cellular and molecular mechanisms whereby folate counteracts age-related disease. An increase in homocysteine levels is a major consequence of folate deficiency that may have adverse effects on multiple organ systems during aging. Humans with inherited defects in enzymes involved in homocysteine metabolism, including cystathionine β-synthase and 5,10-methylenetetrahydrofolate reductase, exhibit features of accelerated aging and a marked propensity for several age-related diseases. Homocysteine enhances accumulation of DNA damage by inducing a methyl donor deficiency state and impairing DNA repair. In mitotic cells such DNA damage can lead to cancer, while in postmitotic cells such as neurons it promotes cell death. The emerging data strongly suggest that elevated homocysteine levels increase the risk of multiple age-related diseases, and point to dietary supplementation with folate as a primary means of normalizing homocysteine levels and increasing healthspan.

KW - DNA repair

KW - Folate deficiency

KW - Homocysteine

UR - http://www.scopus.com/inward/record.url?scp=0036484629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036484629&partnerID=8YFLogxK

U2 - 10.1016/S0047-6374(01)00365-7

DO - 10.1016/S0047-6374(01)00365-7

M3 - Article

C2 - 12039451

AN - SCOPUS:0036484629

VL - 1

SP - 95

EP - 111

JO - Ageing Research Reviews

JF - Ageing Research Reviews

SN - 1568-1637

IS - 1

ER -