INFLUENCE OF GDF-11 IN AGING PROCESS : AN REVIEW

 

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ABOUT AUTHORS
Devender Sharma*,  Dr. Satish Kosalge1, Snehal R. Dixit1
Hi – Tech college of pharmacy, Chandrapur (M.S.)
*sdevender350@gmail.com

ABSTRACT
Aging is one of the phases of individual’s life span, which everyone wants to escape. The process of aging is much more a social phenomena than biological phenomena. Aging brings many changes such as, loss of eyesight, hearing loss, dementia, etc. Aging may give rise to diseased states such as, heart disease, cancer, cerebrovascular disease (relating to blood vessels that supply the brain), pneumonia and flu, and chronic obstructive pulmonary diseases. The key-factor behind aging is the GDF11, i.e., Growth and Differentiation factor-11. GDF11 is also known as Bone Morphogenetic Factor-11 (BMP11). It is termed as key circulating ‘anti-aging’ factor. GDF11 is expressed in wide range of tissues and has been shown to play important roles in development of olfactory system, retina and pancreas. It functions in regulating anterior-posterior patterning of the axial skeleton muscle system. Scientists theorize that aging likely results from a combination of many factors viz., Lifestyle, Diseases and Genes. GDF11 is essential for mammalian development and has been suggested to regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic processes .

Reference Id: PHARMATUTOR-ART-2546

PharmaTutor (Print-ISSN: 2394 - 6679; e-ISSN: 2347 - 7881)

Volume 5, Issue 12

Received On: 18/08/2017; Accepted On: 18/08/2017; Published On: 01/12/2017

How to cite this article: Sharma D,  Kosalge S, Dixit SR;Influence of GDF-11 in Aging Process : An Review; PharmaTutor; 2017; 5(12); 18-29

INTRODUCTION
A life course is the period from birth to death, including a sequence of predictable life events such as physical maturation and the succession of age-related roles: child, adolescent, adult, parent, senior etc. Aging is one of the phases of individual’s life span, which everyone wants to avoid. The process of aging is much more a social phenomena than biological phenomena. Some people fear old age and do many things to avoid it, seeking medical and cosmetics remedies for the natural effects of age. Normally, aging brings many changes such as, loss of eyesight, hearing loss, dementia, etc. Aging may give rise to diseased states such as, heart disease, cancer, cerebrovascular disease (relating to blood vessels that supply the brain), pneumonia and flu, and chronic obstructive pulmonary diseases. Numbers of psychological problems associated with aging are dementia, depression, anxiety, paranoia, dread, apprehension, sleep problems, behavioral disorders and most commonly Alzheimer’s disease.[1]

Scientists theorize that aging likely results from a combination of many factors viz., Lifestyle, Diseases and Genes. Lifestyle changes and disease condition are the consequences of aging. The key-factor behind aging is the GDF11, i.e., Growth and Differentiation factor-11. GDF11 is also known as Bone Morphogenetic Factor-11 (BMP11). It is termed as key circulating ‘anti-aging’ factor. [1] It is a member of TGF-β super-family and is derived along with myostatin (GDF-8).  GDF11is a protein that, in humans is encoded by the gene GDF11. [3] It acts as a cytokine and its paralog is MSTN gene. [3] It is a myostatin-homologous protein that acts as an inhibitor of nerve tissue growth. [4][17] Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the transforming growth factor β superfamily and are often perceived to serve similar or overlapping roles.[5][6] Both GDF11 and myostatin are synthesized as precursor molecules where an N-terminal pro-domain is cleaved from a C-terminal signaling or mature domain by a furin protease enzyme.[15] GDF11 is essential for mammalian development and has been suggested to regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic processes.[15] In 2014, GDF11 was described as an anti-aging factor in two publications based on results of parabiosis experiments using mice. [5][6] Many other later studies questioned these findings. [7][8][9][10] The actual relationship between GDF11 and the aging continues to be researched. Both GDF11 and myostatin predominantly use the type II receptors activin receptor kinase II-A and type II receptors activin receptor kinase II-B and the type I receptors activin receptor-like kinase 4 (ALK4) and ALK5 to elicit signal transduction via SMAD2 & SMAD3.[11][15][16][17][18] GDF11 also can signal through an additional type I receptor, ALK7.[20] Signaling by GDF11 and myostatin is regulated by extracellular-binding proteins that are typically thought to function as antagonists. These include follistatin, follistatin-like 3 (FSTL3), decorin, and growth/differentiation factor–associated serum proteins 1 and 2 (GASP1 and GASP2).[15][18] GDF11 is involved in cell growth and differentiation, mesodermal formation and neurogenesis (during embryonic development) as well as in cardiac and skeletal muscle aging (anti-hypertrophic effect and anti-rejuvenating effect). [20][21][22][15]  GDF11 is expressed in wide range of tissues and has been shown to play important roles in development of olfactory system, retina and pancreas.[18][26][27][28][29] It functions in regulating anterior-posterior patterning of the axial skeleton muscle system. [33][30]

 

WHAT IS AGEING?
The aging process happens during an individual’s lifespan. We all are involved in this process and no one can escape it. Many people fear old age and do anything to avoid it. The process of aging is a lifelong process and entails maturation and changes in physical, psychological and social patterning of life. Dr. Ignatz Nascher, a New York Physician gave the term geriatrics, a combination of two Greek words: geron (old man) and iatrikos (medical treatment).  He saw the practice of caring for the elderly as separate from the practice of caring for the young, just as pediatrics (caring of children) is different from caring for grown adults.[36] When one is young, aging is associated with growth, maturation, and discovery. In the broader sense, ageing can refer to single cells within an organism which have ceased dividing (cellular senescence) or to the population of a species (population ageing).In humans, aging represents the accumulation of changes, encompassing physical, psychological, and social changes.[57] Ageing is among the greatest known risk factors for most human diseases:[48] roughly 150,000 people who die each day across the globe, about two thirds die from age-related causes.

Scientists theorize that aging likely results from a combination of many factors. Genes, lifestyle, and diseases can all affect the rate of aging. Studies indicate that people age at different rates and in different ways.[56]

Fig.No.1: A 75 year old woman

Effects of aging
A number of characteristic ageing symptoms are experienced by a majority or by a significant proportion of humans during their lifetimes. Normal aging brings about following changes:

• Eyesight- loss of vision or blurred vision and decreased ability to identify objects.[59][60]  More than half, may undergo cataract surgery. [65]    
• Hearing- loss of hearing acuity and decreased ability to distinguish sounds when there is background noise.[64]
• Taste- decreased taste buds and saliva.
• Touch and Smell- decreased ability to smell and sensitivity to touch.
• Arteries- hardening of the arteries, leading to Arteriosclerosis. [68]
• Brain- loses some of the structures that connect nerve cells, thus, diminishing cell functions. High risk of dementia, anxiety, apprehension and behavioral disorders etc.[71][72]
• Bones- lose minerals leading to osteoarthritis. [63]
• Bladder- increased frequency in urination.
• Heart- pumping rate and body’s ability to extract blood diminishes with age. Also higher risk of stroke and heart attacks. [68][69][70]
• Kidneys- shrink and become less efficient.
• Lungs- lung tissue begins to lose its elasticity and bronchial muscle shrink, thus, decreasing breathing capacity.
• Muscles- muscle mass decline. [66][67]
• Skin- nails grow more slowly. Skin is more dry and wrinkled.
• Sexual health- women go through menopause, vaginal lubrication decreases. In men, sperm production decreases and the prostate enlarges. Hormone level decreases.[62][73]
• Hairs- hair turns grey with age. [61]


Fig. No. 2: An old woman with wrinkled face and grey colored hairs

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