Theories of Aging PDF

Theories of Aging Clinical Sciences IV Geriatrics Paul B. Volker, MD, FAAFP Assistant Professor Dept. of Osteopathic Clinical Medicine 29 March 2024 Objective Describe and differentiate the common theories proposed to explain the aging process 29 March 2024 Targeted DNA damage Mitochondrial DNA dama...

Theories of Aging Clinical Sciences IV Geriatrics Paul B. Volker, MD, FAAFP Assistant Professor Dept. of Osteopathic Clinical Medicine 29 March 2024 Objective Describe and differentiate the common theories proposed to explain the aging process 29 March 2024 Targeted DNA damage Mitochondrial DNA damage Free radicals Telomere Transposable Element Activation Volker Theories of Aging Epigenetics Error catastrophe Accumulation Energetics Endocrine Immune/inflammatory Stem cell 2 Consider these No agreement on definition Aging is studied by many of aging different disciplines – Psychology Multiple causes of aging – Sociology Aging is very complex – Immunology (individual + population) – Economics Many possible interactions – Genetics – Biology (environmental + disease) – Medicine – Religion – Political Science 29 March 2024 Volker Theories of Aging 3 One Perspective of Aging Loss of Homeostasis A breakdown in maintenance of specific molecular structures and pathways This breakdown is the inevitable consequence of the evolved anatomy and physiology of an organism Some are unique to the specific cellular and tissue context of a specific organ Some are due to the overall organ system being stressed Geriatric Review Syllabus 10h Edition – Biology Chapter 29 March 2024 Volker Theories of Aging 4 Major Theories of Aging The multitude of theories about why we age are not competing or mutually exclusive; they reflect our current understanding of the multiple factors and mechanisms that happen to us all Two main types of biologic theories of aging – Evolutionary (the “why” of aging) – Physiologic (the “how” of aging) 29 March 2024 Volker Theories of Aging 5 Evolutionary theories Impact of natural selection on the reproductive fitness of a species Two main types – Mutation accumulation Aging viewed as a non-adaptive trait Late-acting genes accumulate – Antagonistic Pleiotropy A single gene controls or influences multiple traits Genes that effect early fitness are harmful in later years Example: Hyperlipidemia 29 March 2024 Volker Theories of Aging 6 Physiologic Theories Targeted DNA damage Mitochondrial DNA damage Free radicals Telomere Transposable Element Activation 29 March 2024 Epigenetics Error catastrophe Accumulation Energetics Endocrine Immune/inflammatory Stem cell Volker Theories of Aging 7 Target Theory of Genetic Damage Damage to our genes from a variety of sources such as radiation or any number of damaging agents (chemicals) causes an alteration in structure and signaling for repair molecules Accumulation of “hits” to the genome Evidence: radiation shortens lifespan due to DNA damage 29 March 2024 Volker Theories of Aging 8 Mitochondrial Damage Damage to mitochondria reduces energy available for metabolism and cellular resilience Overall deleterious results: – Less energy production – More free radical formation – Reduced control of cellular processes – Accumulation of damaged harmful molecules 29 March 2024 Volker Theories of Aging 9 Free Radical Theory Reactive Oxygen Species (ROS) are extremely reactive and unstable and are produced in mitochondria, in oxidative enzymes, in the endoplasmic reticulum, and phagocytes Highly reactive oxygen-derived free radicals damage protein, lipid, and DNA, leading to altered structure and functional capacity Mitochondria particularly susceptible (in this way, similar to Mitochondrial Damage Theory) 29 March 2024 Volker Theories of Aging 10 Telomere Theory Telomeres shorten with each successive mitosis Cellular replicative senescence is triggered when cells acquire critically short telomeres 29 March 2024 Volker Theories of Aging 11 Transposable Element Activation Some individual genes or even portions of chromosomes can be transposed to other locations on its own or other chromosomes May interfere with gene expression This is cumulative over time 29 March 2024 Volker Theories of Aging 12 Epigenetic Theory Gene regulation can vary with age as DNA is methylated or chromatin-bound Some needed genetic expression may be blunted, or harmful expression may be accelerated “Kill Switch” 29 March 2024 Volker Theories of Aging 13 Error Catastrophe Theory Damage is not to the genes themselves but to the RNA and proteins that read the genes and carry out their instructions Damaged transcription can produce abnormal proteins (including the transcription proteins themselves) 29 March 2024 Volker Theories of Aging 14 Accumulation Theories “Clinker Theory” Accumulation of cellular and extracellular components with altered structures that compromise cellular function Detritus like lipofuscin accumulates and no one picks up the trash 29 March 2024 Volker Theories of Aging 15 Energetics Theories “The faster the metabolism, the shorter the life” Higher metabolism required higher oxygen consumption and thus greater exposure to reactive oxygenating species 29 March 2024 Volker Theories of Aging 16 Endocrine Theory With aging, secretion of many hormones change Circadian cycles of certain hormones become irregular – Growth hormone – Sex steroid hormones 29 March 2024 Volker Theories of Aging 17 Immune Theory In response to an agerelated decline in acquired immunity, the innate immune system becomes activated resulting in over vigorous expression of cytokines and inflammatory substances 29 March 2024 Volker Theories of Aging 18 Stem Cell Theory Adult stem cells in the brain, bone marrow, and circulation maintain homeostasis by replenishing depleted reserves As time passes precursor cells become depleted by phenotypic drift, injury, illness, environmental challenges Result is lesser ability to replace cells lost to death or damage 29 March 2024 Volker Theories of Aging 19 Of course, a combination of several of these processes is likely what happens Example – Calorie restriction prolongs life in many organisms – Via reduced ROS, ACCUMULATION, telomere 29 March 2024 Volker Theories of Aging 20 Physiologic Theories Targeted DNA damage Mitochondrial DNA damage Free radicals Telomere Transposable Element Activation 29 March 2024 Epigenetics Error catastrophe Accumulation Energetics Endocrine Immune/inflammatory Stem cell Volker Theories of Aging 21 There is only one intervention in mammals which has been shown to significantly increase lifespan Calorie restriction 29 March 2024 Volker Theories of Aging 22 What Now? Regardless of how the aging process happens, the way your patient handles the changes that come with aging is perhaps the most influential factor in defining the impact on their health Attitude plays a role in several ways, how well your patient lives, but may also play a significant role in how long they may live Successful aging can be thought of as maintaining good health, good functionality, good cognition, and remaining socially engaged 29 March 2024 Volker Theories of Aging 23 Remember Mentation Mobility Medication What Matters Most 29 March 2024 Volker Theories of Aging 24 Watch the Stress Reach out Eat right, exercise, sleep Keep the activities in check Practice forgiveness Change will come, learn to accept Humor What gives meaning to your life Avoid negative people 29 March 2024 Volker Theories of Aging 25 Social / Friendships Extends your healthspan Recovery times Immunity Mental Health – Reduces anxiety – Protects against mental decline – Adapted from Mayo Clinic on Healthy Aging 2013 29 March 2024 Volker Theories of Aging 26 Spirituality Over 50% of older adults report frequent attendance at religious events or practices Death of friends, nearing own death prompt thoughts and questions about afterlife Legacy; what will I leave after I’m gone Invite your chaplains and clergy in I encourage you to explore your own spirituality, get comfortable relating to your patients in this way 29 March 2024 Volker Theories of Aging 27 Challenge Your Patients to “Use it or Lose it” Social support Religion and Spirituality Work your brain (especially learning activities) Work your body Eat well, but not too much Avoid drugs, tobacco, excessive alcohol Small changes add up 29 March 2024 This is pretty good advice for you and me, too! Volker Theories of Aging 28 Too Often Too often we underestimate the power of a touch, a smile, a kind word, a listening ear, an honest compliment, or the smallest act of caring, all of which have the potential to turn a life around Leo Buscaglia 29 March 2024 Volker Theories of Aging 29 Don’t forget to call Parents Grandparents Mentors Good friends 29 March 2024 Volker Theories of Aging 30