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An Update on the Molecular Pillars of Aging

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Clinical Genetics and Genomics of Aging

Abstract

The human life span has been continually increasing as a result of favorable lifestyle factors, health care and medical advances and has consequences that include an increased incidence of age-associated diseases. The onset of osteoporosis, arthritis, cataracts, and cardiovascular and neurodegenerative diseases is strongly associated with the aging process, which is a multifactorial condition characterized by genome and proteome instability, mitochondrial dysfunction, metabolic deregulation, and cellular senescence. The remarkable impact of aging on the development of these progressive diseases highlights the need to understand the mechanisms that underlie the aging process and human longevity. In this chapter, we aim to summarize the main molecular and cellular processes that are involved in the regulation of aging and that may have implications for the development of therapeutic tools that decelerate senescence and improve human health.

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Abbreviations

53BP1:

Tumor suppressor p53-binding protein 1

5mC:

5-Methylcytosine

AD:

Alzheimer’s disease

ADP:

Adenosine diphosphate

AICAR:

5-Aminoimidazole-4-carboxamide ribonucleotide

AKT:

Protein kinase B, also called PKB

AMP:

Adenosine monophosphate

AMPK:

AMP-activated protein kinase

ANT2:

Adenine nucleotide translocator 2

ARF:

ADP-ribosylation factor

ATP:

Adenosine triphosphate

BRASTO:

Brain-specific SIRT1-overexpressing transgenic mice

CDk:

Cyclin-dependent kinase

circRNA:

Circular RNA

CNV:

Copy number variant

COX:

Cyclooxygenase

CpG dinucleotide:

Cytosine nucleotide followed by a guanine nucleotide in the linear sequence of bases along its 5′ → 3′ direction

CR:

Calorie restriction

DDR:

DNA damage response

FOXO:

Forkhead box O

HLA-E:

Major histocompatibility complex class I antigen E

HP1:

Heterochromatin protein 1

IGF:

Insulin growth factor 1

IL:

Interleukin

LHON:

Leber hereditary optic neuropathy

LINE:

Long interspersed nuclear element

lncRNA:

Long noncoding RNA

MBD1:

Methyl-CpG-binding domain protein

MDC1:

Mediator of DNA damage checkpoint protein 1

MELAS:

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

MFRTA:

Mitochondrial free radical theory of aging

miRNA:

MicroRNA

mtDNA:

Mitochondrial DNA

mTOR:

Mammalian target of rapamycin

mTORC:

Mammalian target of rapamycin complex

NAD+:

Nicotinamide adenine dinucleotide

NBS1:

Nibrin protein

NFƙB:

Nuclear factor ƙB

NR4A:

Nuclear receptor subfamily 4 group A member

NRF2:

Transcription factor named nuclear factor E2-related factor 2

PI3K:

Phosphatidylinositol 3-kinase

POT1:

Protection of telomeres 1 protein

ROS:

Reactive oxygen species

S6K:

Ribosome S6 kinase

SASP:

Senescence-associated secretory phenotype

SIRT:

Sirtuin

SNV:

Single-nucleotide variant

TERC:

Template telomerase RNA component

TFRC:

Transferrin receptor

TGF-β:

Transforming growth factor-β

TIN2:

TRF1-interaction nuclear factor 2

TOX:

Thymocyte selection-associated high mobility group box protein

TPE:

Telomere position effect

TPP1:

Tripeptidyl-peptidase 1

TRF1:

Telomeric repeat binding factor 1

UPS:

Ubiquitin-proteasome system

VEGF:

Vascular endothelial growth factor

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Acknowledgments

Our apologies to the authors whose work we could not cite due to space constraints.

This work was supported by CONACYT, A1-S-9559.

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Authors and Affiliations

  1. Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Lizbeth García-Velázquez & Clorinda Arias

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  1. Lizbeth García-Velázquez
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  2. Clorinda Arias
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Correspondence to Lizbeth García-Velázquez .

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  1. Basic Sciencies Division, National Institute of Geriatrics, Ciudad de México, Mexico

    Juan Carlos Gomez-Verjan

  2. Instituto Nacional de Geriatría (INGER), Ciudad de México, Mexico

    Nadia Alejandra Rivero-Segura

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García-Velázquez, L., Arias, C. (2020). An Update on the Molecular Pillars of Aging. In: Gomez-Verjan, J., Rivero-Segura, N. (eds) Clinical Genetics and Genomics of Aging. Springer, Cham. https://doi.org/10.1007/978-3-030-40955-5_1

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